Myelolytic Treatments Enhance Oncolytic Herpes Virotherapy in

Original Article

Myelolytic Treatments Enhance Oncolytic Herpes Virotherapy in Models of Ewing Sarcoma by Modulating the Immune Microenvironment Nicholas L. Denton,1 Chun-Yu Chen,1 Brian Hutzen,1 Mark A. Currier,1 Thomas Scott,1 Brooke Nartker,1 Jennifer L. Leddon,1 Pin-Yi Wang,1 Rachelle Srinivas,1 Kevin A. Cassady,1 William F. Goins,2 and Timothy P. Cripe1 1Center

for Childhood Cancer and Blood Diseases, Nationwide Children’s Hospital, The Ohio State University, Columbus, OH 43205, USA; 2Department of Microbiology

and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA

Ewing sarcoma is a highly aggressive cancer that promotes the infiltration and activation of pro-tumor M2-like macrophages. Oncolytic virotherapy that selectively infects and destroys cancer cells is a promising option for treating Ewing sarcoma. The effect of tumor macrophages on oncolytic virus therapy, however, is variable among solid tumors and is unknown in Ewing sarcoma. We tested the effects of macrophage reduction using liposomal clodronate (Clodrosome) and trabectedin on the antitumor efficacy of intratumoral oncolytic herpes simplex virus, rRp450, in two Ewing sarcoma xenograft models. Both agents enhanced antitumor efficacy without increasing virus replication. The most profound effects were in A673 with only a transient effect on response rates in TC71. Interestingly, A673 was more dependent than TC71 on macrophages for its tumorigenesis. We found Clodrosome and virus together induced expression of antitumorigenic genes and reduced expression of protumorigenic genes in both the tumor-associated macrophages and the overall tumor stroma. Trabectedin reduced intratumoral natural killer (NK) cells, myeloid-derived suppressor cells, and M2-like macrophages, and prevented their increase following virotherapy. Our data suggest that a combination of trabectedin and oncolytic herpes virotherapy warrants testing in the clinical setting.

INTRODUCTION Ewing sarcoma is an aggressive bone or soft tissue tumor predominantly found in adolescents and young adults. Despite the aggressive use of surgical resection, irradiation, and chemotherapy, outcomes are unacceptable with 5-year survival rates for patients with localized and metastatic disease less than 70% and 30%, respectively.1,2 The characteristic translocation between chromosomes 11 and 22, resulting in the EWS/FLI fusion protein, or similar translocations between EWS and other members of the ETS family of transcription factors, are pathognomonic oncogenes that aberrantly regulate gene expression.3,4 Among their pleiotropic effects is enhanced macrophage chemokine expression promoting pro-tumor M2-like macrophage activation.5,6 In fact, in a small pilot study, the 5-year overall survival rate dropped from 70% to 20% in patients with localized disease who had greater than 30 CD68+ macrophages per 0.64 mm2 high-power

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field in their tumor biopsies.1 Thus, tumor-associated macrophages may be an attractive therapeutic target. Another promising strategy to treat aggressive cancer is the emerging field of oncolytic viruses that selectively replicate in and destroy cancer cells. Oncolytic virotherapy is characterized by direct infection of cancer cells and stimulation of a host antitumor immune response.5,7,8 There is a growing number of clinical trials for oncolytic virus therapy that demonstrate safety in adult and childhood cancer patients, leading to the first Food and Drug Administration-approved oncolytic virus, Talimogene laherparepvec (T-VEC), for the treatment of metastatic melanoma.9–11 With these recent breakthroughs, oncolytic virotherapy has the potential to become a new therapy option for a wider variety of patients with solid tumors. Interestingly, macrophages have variable effects on oncolytic virotherapy, although their interactions in Ewing sarcoma have not been investigated. Although M2-like tumor macrophages are generally tumor promoting by suppressing the host antitumor immune response, they also suppress the host antiviral immune response that inhibits the direct oncolytic effect of virotherapy.5,12–14 M1like tumor macrophages are generally tumor suppressive by activating the host antitumor immune response; however, they can also enhance the antiviral immune response and inhibit the oncolytic effect of virotherapy.5,15,16 Within the categories of classically activated inflammatory M1 macrophage and alternatively activated immune suppressive M2 macrophage there are non-canonical subtypes of M1-like and M2-like macrophages that utilize different mechanisms of immune stimulation and suppression, depending on how the microenvironment stimulates the macrophages.17,18 These non-canonical activation states include the M1-like M(lipopolysaccharide [LPS]), M(interferon-gamma [IFNg]), and M(LPS+IFNg), along with the M2-like M(IL-10), M(IL-4), M(transforming growth

Received 5 July 2018; accepted 13 October 2018; https://doi.org/10.1016/j.omto.2018.10.001. Correspondence: Timothy P. Cripe, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA. E-mail: [email protected]

Molecular Therapy: Oncolytics Vol. 11 December 2018 ª 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

www.moleculartherapy.org

Figure 1. Clodrosome Depletion of Macrophages Enhances OV Efficacy (A) Treatment regimen of A673 tumor xenograft-bearing mice given 400 mg of liposome or Clodrosome intravenously (i.v.) on day 3 and intraperitoneally (i.p.) on days 2, 1, and 0 followed by weekly i.p. treatments. Oncolytic herpes simplex virus rRp450 was given at 107 pfu intratumorally (i.tu.) on days 0 and 2. (B) A673 flank tumors treated with the above regimen were measured until tumors reached an endpoint volume of 2,000 mm3. Both tumor growth curves with SEMs and Kaplan-Meier plots of survival are shown. Error bars indicate SEM. (C) Virus replication in A673 xenografts treated with the above Clodrosome regimen and a single 107 pfu dose of rRp450 given intratumorally (i.t.) at the time points indicated prior to tumor homogenization and plaque assay. Statistical analyses of survival curves were performed using Mantel-Cox test, and bar graphs were done using unpaired multiple two-tailed t test; *p < 0.05, **p < 0.005, ***p < 0.0005. Error bars indicate SD.

factor-b [TGF-b]), and M(immune complex).19–21 Therefore, a thorough analysis of the interactions between tumor cells, macrophages, and oncolytic viruses is required to understand how tumor macrophages affect oncolytic virus efficacy. We previously showed that direct injection of oncolytic herpes virus into models of Ewing sarcoma is only partially effective at slowing tumor growth, in part due to unknown effects of infiltrating CD11b+ myeloid cells.22 To determine whether the effect was due to macrophages, here we used two macrophage-reducing strategies, including the well-known agent liposomal clodronate (Clodrosome), which poisons mitochondrial electron transport and, due to its liposomal formulation, is selectively taken up by phagocytic cells, and trabectedin, which has also been shown to reduce tumor-associated macrophages. In combination with virotherapy, these agents markedly increased antitumor efficacy and were associated with a significantly altered tumor microenvironment. The combination induced expression of antitumorigenic genes and reduced expression of protumorigenic genes in both the tumor-associated macrophages and the overall tumor stroma. Trabectedin reduced intratumoral natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs), and M2-like macrophages, and prevented their increase following virotherapy. Our data provide rationale for clinical trials of oncolytic virotherapy with macrophage-targeted therapy.

RESULTS Clodrosome Depletion of Macrophages Enhances Oncolytic Virus Efficacy

In order to determine the effect of tumor macrophages on oncolytic virus efficacy in a model of Ewing sarcoma, we used a regimen of macrophage-depleting liposomal clodronate (Clodrosome) prior to oncolytic herpes simplex virus infection. We treated athymic nude mice previously implanted with A673 xenograft tumors with a combination of intravenous and intraperitoneal Clodrosome or liposome control prior to two intratumoral doses of rRp450, a herpes simplex type 1 virus attenuated by deletion of the virus gene encoding the large subunit of ribonucleotide reductase,23,24 or PBS control (Figure 1A). Clodrosome treatment alone did not impact established A673 xenograft growth, while macrophage-intact liposome-treated xenografts experienced a tumor growth delay with a few complete responses (CRs) (3/14 CR) following rRp450 injection (Figure 1B). When we depleted macrophages with Clodrosome prior to rRp450 injection, however, we found that the majority of A673 xenografts shrank to CR (8/14 CR). Although we hypothesized that the improved antitumor efficacy of oncolytic virus with macrophage depletion was likely due to increased virus production and/or spread, given that macrophages are known to phagocytose virus-infected cells,14,25 we did not observe a significant impact of macrophage depletion on rRp450 replication kinetics in A673 xenografts except after 144 hr, at which time the amount of virus recovered from tumors was even

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Figure 2. Clodrosome Reduces Systemic and Intratumoral Macrophages (A and B) Flow cytometry quantification of total splenocytic (A) and tumor (B) macrophage infiltration and macrophage M1-like and M2-like phenotype infiltration in A673 xenografts on days 0, 5, and 25 in the single intratumorally (i.tu) rRp450 treatment regimen done in Figure 1C. Statistical analysis of bar graphs was done using unpaired multiple two-tailed t test; *p < 0.05, **p < 0.005, ***p < 0.0005.

less in the Clodrosome group (Figure 1C). These data suggest that tumor macrophages diminish the effects of virotherapy through mechanisms other than inhibiting oncolysis. We sought to determine the effects of Clodrosome on systemic (splenic) and tumor macrophages, specifically M1-like versus M2like macrophage populations. We used flow cytometry to analyze leukocyte populations (see gating strategy in Figure S1) in mouse spleens and rRp450-infected A673 tumors, and found that Clodrosome induced significant depletion of both M1-like (CD11c+/ CD206 ) and M2-like (CD11c+/CD206+) splenic macrophages (Figure 2A). Interestingly, the tumor macrophages were only partially depleted (50%; Figure 2B). Because M2-like tumor macrophages were approximately 10-fold higher in abundance compared with M1-like tumor macrophages, we postulated that the M2-like tumor macrophages are responsible for limiting the efficacy of oncolytic virus therapy in A673 tumors. Clodrosome Depletion of Macrophages Prevents A673 Tumorigenesis

Given the importance of macrophages in restricting response to virotherapy in A673, we sought to determine their importance in tumorigenesis of this model. We pretreated athymic nude mice with a similar regimen of intravenous and intraperitoneal Clodrosome prior to subcutaneous implantation of Ewing sarcoma cells into the flank (Figure 3A). The macrophage intact mice treated with liposome control quickly formed tumors that reached endpoint criteria within

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20 days (Figure 3B). However, the mice we pre-treated with Clodrosome experienced a significant delay in tumor formation, with 50% failing to establish a tumor until >60 days after A673 cell implantation. We again noted that Clodrosome reduced splenic macrophages and had some impact on NK cell and MDSC populations as well (Figure 3C). Interestingly, the few tumors that formed 10 days after A673 implantation in the Clodrosome-treated mice acquired tumor macrophages comparable with the liposome control-treated tumors (Figure 3D); this finding may be due to variability in Clodrosome stability or the ability of residual macrophages in the flank to assist in tumor formation. These results suggest that tumor macrophages are required for Ewing sarcoma tumorigenesis in this model. M2-like Macrophages Interfere with Virus Cytotoxicity

The similar recovery of infectious virus from tumors suggested that macrophages do not affect virus-mediated oncolysis in the A673 model. To confirm this finding, we assessed whether macrophages in isolation could limit the effects of virus-mediated oncolysis by evaluating oncolytic virus cytotoxicity in Ewing sarcoma cells cultured with bone marrow-derived macrophages (BMDMs) stimulated under various conditions. We isolated murine BMDMs and stimulated them under conditions expected to polarize macrophages toward an M2-like phenotype (IFNg, LPS, and IFN+LPS), toward an M1-like phenotype (interleukin-10 [IL-10], IL-4, TGF-b), or left them unstimulated to serve as a baseline control. To determine the effects the different conditions had on gene expression patterns, we created a 96-gene PCR array including known macrophage and


Figure 3. Clodrosome Depletion of Macrophages Impairs A673 Tumorigenesis (A) Treatment regimen of athymic nude mice given 400 mg of liposome or Clodrosome intravenously (i.v.) on day 3 and intraperitoneally (i.p.) on days 2, 1, and 0 followed by weekly i.p. treatments. A673 Ewing sarcoma cells were implanted subcutaneously into the flank on day 0. (B) A673 flank tumors treated with the above regimen were measured until tumors reached an endpoint volume of 2,000 mm3. Flow cytometry quantification of (C) splenocytic and (D) tumor leukocyte infiltrates in A673 tumors 10 days after A673 cell implantation. Statistical analyses of survival curves were done using Mantel-Cox test, and bar graphs were performed using unpaired multiple two-tailed t test; *p < 0.05, **p < 0.005, ***p < 0.0005. Error bars indicate SD.

cancer-relevant murine genes. After normalizing gene expression to the internal actin control, we performed an unsupervised clustering of genes that showed significant changes across the different conditions (Figure 4A). The results showed a cluster of genes that were mostly activated following exposure to the LPS and/or IFNg stimuli (top of Figure 4A), genes that were indiscriminately expressed regardless of stimulation (middle of Figure 4A), and genes preferentially activated following exposure to IL-4, IL-10, or TGF-b (bottom of Figure 4A). We then directly cocultured these differently stimulated macrophages with A673 cells prior to rRp450 virus infection and semi-daily cytokine supplementation, and measured cell viability relative to uninfected, unstimulated cocultures (Figure 4B). Interestingly, we found that IFNg and TGF-b alone resulted in some degree of cytotoxicity (compare uninfected black bars in Figure 4B). In addition, we found that unstimulated macrophages as well as macrophages stimulated with IFNg (alone or, to a lesser degree, with LPS) or with IL-4 caused further cytotoxicity, suggesting that these cells are capable of recognizing and phagocytosing stressed cancer cells. These data suggest that different macrophage phenotypes may differ in their anti-cancer activity. Interestingly, while virus infection reduced cell viability in all cases compared

with uninfected cells in the absence of macrophages (black bars in oncolytic herpes simplex virus [oHSV] groups; Figure 4B), the addition of co-cultured cells did not affect virus-mediated cell killing in any of the conditions. This finding is consistent with our in vivo data suggesting that macrophage reduction via Clodrosome did not change virus-mediated oncolysis. Clodrosome and Virotherapy Independently Modulate Tumor Macrophages and the Stromal Microenvironment

Because Clodrosome only partially reduced the numbers of intratumoral macrophages, we sought to determine any changes in the phenotype of residual tumor-associated macrophages in the different treatment groups. To do so, we isolated F4/80+ cells from harvested tumors by magnetic bead selection and analyzed the same genes from our in vitro study using the qPCR gene array and normalized gene expression to the actin control. We were unable to match the cell populations from any of the groups with any of the patterns of expression we found in our prior in vitro study using cytokinestimulated bone marrow-derived macrophages, suggesting (not surprisingly) that tumor-associated macrophages are comprised of a mixed population of different phenotypes. Instead, we sought to


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Figure 4. Bone Marrow-Derived Macrophages Alter Phenotypes in Response to Exogenous Stimuli But Do Not Affect Viral Oncolysis (A) F4/80+ bone marrow-derived macrophages were isolated and grown in 10F DMEM unstimulated or stimulated with LPS, IFNg, LPS+IFNg, IL-4, IL-10, or TGF-b and analyzed for gene expression. (B) A673 Ewing sarcoma cells were cultured alone or cocultured with the different macrophage populations and infected with rRp450 for 6 days before performing MTS viability assays. Statistical analysis of viability curves was performed using ANOVA; *p < 0.05, **p < 0.005, ***p < 0.0005. Error bars indicate SD.

determine changes in gene expression in the combination group (Clodrosome+oHSV), in which we saw significant antitumor activity, compared with the other groups. We normalized the expression of each gene to the control group (liposome/PBS) and sorted their expression from high to low in the combination group. As shown in Figure 5, 15/26 genes associated with known anti-tumorigenic activity increased, 5/26 remained unchanged, and 6/26 decreased in the combination group. Conversely, in 10/23 pro-tumorigenic activity increased, 3/23 remained unchanged, and 10/23 decreased in the combination group. Interestingly, most of the changes in gene expression were not shared in either of the single-agent treatment groups, suggesting that both Clodrosome and virus acted in concert to alter macrophage phenotypes. We also found expression of virus genes in virus-treated tumors, suggesting that macrophages are either directly infected or phagocytose virus-infected cells following intratumoral virus injection.

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The use of human tumor xenograft models in mice enables us to assess changes in gene expression specifically in the microenvironment, distinct from cancer cells, by measuring changes in mouse genes. In addition to analyzing isolated tumor-associated macrophages, we also analyzed the entire tumor microenvironment using the qPCR microarray in a separate cohort of tumors. Similar to our findings in macrophages, the tumor microenvironment in the combination group was highly inflamed, with marked activation of anti-tumorigenic genes and suppression of pro-tumorigenic genes (Figure 6). These changes mirrored but were even more dramatic in numbers of genes and fold changed than those in the F4/80+ macrophages. In the microenvironment as a whole, 17/26 genes associated with known anti-tumorigenic activity increased, 7/26 remained unchanged, and 2/26 decreased in the combination group. Conversely, 6/23 pro-tumorigenic activity increased, 8/23 remained unchanged, and 9/23 decreased in the


Figure 5. Clodrosome Plus Virus Alter the Phenotypes of Tumor-Associated Macrophages qPCR array of macrophage activity in F4/80+ tumor macrophages isolated from A673 xenografts treated under the regimen in Figure 1A at 5 days after the first rRp450 infection. Gene expression was normalized within each sample to actin; then the expression of each gene was normalized to that gene’s expression in the control liposome/ PBS group. Genes were sorted based on their expression in the combination Clodrosome/oHSV group.

combination group. Again, many of the changes were not reflected in either of the single-treatment groups. Our findings suggest that reduction of macrophages by Clodrosome enabled cells in the microenvironment to react to virus infection more profoundly, either directly or indirectly. We noted that one of the genes decreased by Clodrosome in the microenvironment was TGF-b. We previously reported TGF-b signaling inhibited oncolytic virus efficacy in immunocompetent rhabdomyosarcoma models.26 Therefore, we also inhibited A673 TGF-b receptor family signaling using the small molecular inhibitor, A8301, as we had in that study, in combination with oncolytic virus infection. In contrast with our findings in the immunocompetent sarcoma model, in this T cell-deficient setting we did not observe a significant change in tumor response to oncolytic virus therapy (Figure S2).

Trabectedin-Mediated Macrophage Modulation Enhances rRp450 Efficacy

Although Clodrosome is a useful tool for depleting macrophages in animal models, we sought a clinically relevant approach that might be useful in combination with virotherapy. Trabectedin is a chemotherapeutic that has been previously shown to deplete tumor macrophages.27 While trabectedin is currently FDA approved for liposarcoma, there is a growing body of preclinical research demonstrating therapeutic efficacy in Ewing sarcoma,28–31 thought to be due to the interruption of the transcriptional activation by EWS-FLI1. For these reasons we sought to test the combination of trabectedin and oncolytic virus therapy against Ewing sarcoma. We administered A673 xenograft-bearing athymic nude mice with two doses of intravenous trabectedin on days 0 and 7, along with


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Figure 6. Clodrosome Plus Virus Alter the Tumor Stromal Microenvironment qPCR array with mouse-specific primers of whole A673 tumor powder treated under the regimen in Figure 1A at 5 days after first rRp450 infection. Gene expression was analyzed as in the legend of Figure 5.

two doses of intratumoral rRp450 on days 0 and 2 (Figure 7A). Similar to Clodrosome and consistent with prior reports, we found trabectedin reduced tumor-associated macrophages (Figure 7B). Interestingly, trabectedin primarily reduced M2-like macrophages, but not M1-like macrophages, whereas Clodrosome reduced both. We also noted that trabectedin reduced NK cells and MDSCs. While trabectedin alone had no effect on established A673 tumor growth, the combination of trabectedin with rRp450 significantly improved mouse survival compared with oncolytic virus therapy alone (Figure 7C). As with Clodrosome, the effect did not appear to be due to differences in virus-mediated oncolysis because we did not observe any differences in live virus recovered from tumors (Figure 7D). Finally, we sought to test our findings in a second model of Ewing sarcoma to determine the generalizability of our findings. We found the TC71 model to be less dependent on macrophages for growth, as evidenced by the lack of a statistical difference in the delay of the

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appearance and growth rate of tumors in the pre-implantation Clodrosome treatment (Figure 8A), in contrast with A673. Similarly, although there was a trend toward improved virotherapy efficacy when combined with Clodrosome, the differences in tumor growth rates and animal survival also did not reach statistical significance (Figure 8B). Regarding therapeutic efficacy, virotherapy alone had a more profound effect on slowing tumor growth in TC71 (Figure 8C) than in A673, and although the addition of trabectedin resulted in more initial responses than virotherapy alone (5/12 [42%] CRs and 5/12 [42%] partial responses in the combination for a total of 84% response rate, compared with 2/8 [25%] CRs and 1/8 [12.5%] partial responses for a total of 37.5% response rate), there was no difference in overall animal survival. These data are all consistent with the idea that tumor models dependent on macrophages for progression may be less responsive to virotherapy but can be rendered more susceptible by modulating the tumor-associated macrophages and the immune microenvironment with Clodrosome or trabectedin.


Figure 7. Trabectedin Enhances Oncolytic Herpes Virus Efficacy (A) Treatment regimen of A673 tumor xenograft-bearing mice given 0.15 mg/kg trabectedin intravenously (i.v.) on days 0 and 7. Oncolytic herpes simplex virus rRp450 was given at 107 pfu intratumorally (i.tu.) on days 0 and 2. (B) Flow cytometry quantification of tumor leukocyte infiltrates in A673 tumors on day 3. (C) A673 flank tumors treated with the above regimen were measured until tumors reached an endpoint volume of 2,000 mm3. Statistical analyses of survival curves were performed using the Mantel-Cox test, and bar graphs were done using unpaired multiple two-tailed t test; *p < 0.05, **p < 0.005. (D) Virus replication in A673 xenografts treated with or without trabectedin and a single 107 pfu dose of rRp450 given i.t. at the time points indicated prior to tumor homogenization and plaque assay. Error bars indicate SD.

DISCUSSION Here we report that xenograft models of Ewing sarcoma are variably dependent on macrophages for tumorigenesis, and systemic strategies to diminish macrophages enhance the antitumor response to oncolytic herpes virotherapy without changes in the kinetics of virus replication. Instead, we found that the combination of Clodrosome or trabectedin with virotherapy markedly altered the phenotype of tumor-associated macrophages and the tumor stroma toward a more inflammatory state, as well as altered the cellular immune microenvironment. Our data suggest that a deeper understanding of the biology of tumor-associated macrophages in the context of oncolytic virotherapy is warranted. While the importance of non-canonical macrophage activity has been recognized in the field of trauma and wound heal-

ing research, there have been few studies of the impact of noncanonical macrophages on tumor progression and immunotherapy.19,21,32 Although IL-12 expressing oHSV has been shown to induce phosphorylated signal transducer and activator of transcription 1 (p-STAT1)+/inducible nitric oxide synthase (iNOS)+ M1-like macrophage polarization, the additional inhibition of immune checkpoint signaling was required to improve oncolytic virus (OV) antitumor efficacy in glioblastoma models.33 M1-like p-STAT1/3+ tumor-associated macrophages (TAMs) have also been shown to inhibit oHSV replication in infected macrophages, suggesting that viral genes found in infected A673 macrophages are not likely replicating virus.34 There is also evidence that individual macrophages can be simultaneously stimulated into M1-like and M2-like activity during wound healing.19,20 Even though transcriptional analysis of individual macrophages was outside the scope of


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Figure 8. The Ewing Sarcoma Model TC71 Is Less Dependent on Macrophages and More Susceptible to Oncolytic Virotherapy (A) Animals were pretreated with Clodrosome or its control liposome using the regimen in Figure 3A and monitored for tumor development and growth. NSp = 0.1359. (B) TC71 tumor-bearing animals were treated as in Figure 1A and followed for tumor growth and animal survival. p = 0.2 for Lip/PBS compared with Clod/PBS; p = 0.07 for Lip/PBS compared with Lip/oHSV. (C) TC71 tumor-bearing animals were treated as in Figure 7A and followed for tumor growth and animal survival. NS, not significant. **p < 0.005, ***p < 0.0005. Error bars indicate SD.

this project, it would be interesting to determine whether individual tumor macrophages can act simultaneously as M1-like and M2-like macrophages. Our findings also strongly support the combination therapy of oncolytic herpes simplex virus and trabectedin to improve Ewing sarcoma treatment. Trabectedin is a DNA intercalation chemotherapeutic that is particularly attractive for Ewing sarcoma because it disrupts EWS/FLI1 transcription; in some models, such activity results in single-agent activity,28–31 although we did not observe any efficacy of trabectedin alone in A673 or TC71 despite administering doses previously shown to reduce EWS/FLI1 expression. In addition to inhibiting EWS/FLI-mediated tumor progression, trabectedin also depletes TRAILR2+ tumor leukocytes, such as macrophages and MDSCs.27,35,36 Interestingly, in addition to effects on these cell populations, we also observed trabectedin-mediated depletion of NK cells that has not been previously reported. Although trabectedin as a

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monotherapy was insufficient in reducing A673 tumor xenograft growth, it enhanced oncolytic herpes simplex virus antitumor efficacy similar to the effects we observed with Clodrosome. The additional depletion of MDSCs is also likely to play a role, considering that MDSCs tend to differentiate into pro-tumorigenic M2-like macrophages.37–39 One of the limitations in Ewing sarcoma research is the lack of immunocompetent animal models. Despite extensive study of the translocation resulting in the EWS/FLI protein, the cell of origin for Ewing sarcoma remains elusive.40,41 Although this knowledge gap limits study of in vivo T cell interaction in animal models of Ewing sarcoma, it is known that M1-like and M2-like tumor macrophages strongly influence the activation of CD8+ and regulatory T cells, respectively.42–44 Therefore, we postulate that the phenotypic changes in gene expression we measured in tumor macrophages and the immune microenvironment will increase CD8+ T cell activation in immunocompetent


Ewing sarcoma patients and further enhance the virus-induced antitumor immune response we observed in the athymic nude mouse model. However, it must also be noted that both trabectedin and oncolytic virus therapy can increase immune checkpoint inhibition signaling, which may inhibit T cell activation against tumor antigens.35,45–49 It would be interesting to determine the efficacy of immune checkpoint inhibition in combination with trabectedin and oncolytic virus therapy in immunocompetent pediatric sarcoma models.

trogen), and TC71 was cultured in RPMI medium (Invitrogen) supplemented with 10% FBS. New stocks of cell lines were thawed every five to eight passages in vitro (approximately 1 month). The oncolytic virus rRp450, attenuated by insertion of the rat cytochrome p450 CYP2B1 gene into the viral ribonucleotide reductase ICP6 gene, was provided by E. Antonio Chiocca (Brigham and Women’s Hospital, Boston, MA, USA). All virus stocks were produced and purified by the Virus Production Core at the University of Pittsburgh, School of Medicine.

Overall, our data suggest that the presence of immunosuppressive tumor macrophages in Ewing sarcoma may be a potential biomarker for patients who would benefit from a combination of trabectedin and oncolytic virus therapy. Trabectedin and oncolytic herpes simplex virus combination therapy greatly increased survival of mice implanted with Ewing sarcoma xenografts that exhibited a strong macrophage dependence. Our data support examining a larger panel of pediatric sarcomas to validate macrophage effects on oncolytic virus antitumor efficacy and determine the probable success of a clinical trial combining trabectedin and oncolytic virus therapy in pediatric sarcoma patients.

Compounds and Reagents

MATERIALS AND METHODS Experimental Design

The objectives of this study were to determine the effect of macrophages on oncolytic virus antitumor efficacy in Ewing sarcoma xenografts and design a combination therapy to enhance therapeutic outcome in Ewing sarcomas that exhibit macrophage-dependent inhibition of oncolytic virus therapy. We pursued these objectives by treating athymic nude mice bearing Ewing sarcoma xenografts with oncolytic virus and macrophage-depleting drugs, and recording tumor progression (n = 12–14, endpoint at tumor volume >2,000 mm3 or day >60), leukocyte infiltration (n = 2–5), and virus replication (n = 4–6). We determined the effect of macrophage activity on oncolytic virus antitumor efficacy by coculturing oncolytic virus-treated Ewing sarcoma cells with bone marrow-derived macrophages (n = 6) and then performing qPCR array analysis of whole tumor and F4/80+ macrophage activation, viral infection, and antitumor gene expression (n = 3–6). Treatment group was assigned through simple randomization of each mouse bearing a xenograft ranging from 150 to 250 mm3. Flow cytometry analyses were blinded to treatment group. Outliers were defined as having a value greater than 3 SDs from the mean. Each graph is the accumulation of two to three experimental replicates. Cell Lines and Virus

The A673 human Ewing sarcoma cell line and Vero green monkey kidney cell line were purchased from American Type Culture Collection (Manassas, VA, USA). The TC71 human Ewing sarcoma cell line was obtained from the Children’s Oncology Group repository (https://www.cccells.org). The identities of cell lines were confirmed by short tandem repeat (STR) genotyping, and mycoplasma testing was performed monthly via PCR. A673 and Vero cell lines were cultured in DMEM (Invitrogen) supplemented with 10% FBS (Invi-

Liposomal clodronate (Clodrosome) and control liposome were purchased from Encapsula NanoSciences (Brentwood, TN, USA). Cytokines were purchased through PeproTech (Rocky Hill, NJ, USA). Trabectedin was generously provided by Janssen Pharmaceutical Companies of Johnson and Johnson (Titusville, NJ, USA). For in vivo studies, trabectedin provided by Janssen Pharmaceutics was formulated daily at 0.0375 mg/mL in sterile purified water. Animal Studies

All animal studies were approved by the Institutional Animal Care and Use Committee (IACUC protocol AR12-00074) for the Research Institute at Nationwide Children’s Hospital. Female athymic nude mice, aged 4–6 weeks and weighing 15–25 g, were purchased from Envigo (Indianapolis, IN, USA). These mice were subcutaneously injected with 5.0 106 A673 or TC71 cells in a 150-mL mix of PBS and matrigel (2:1). Preformulated Clodrosome or control liposome was injected intravenously and intraperitoneally prior to rRp450 intratumoral infection for efficacy studies or Ewing sarcoma cell subcutaneous flank implantation for tumorigenesis studies as described in the figure legends. A8301 TGF-b receptor superfamily inhibitor (Sigma-Aldrich) was formulated at 5.0 mg/mL in DMSO. A8301 or equal volume of plain DMSO was diluted in PBS to 6 mg/kg A8301 and administered intraperitoneally thrice weekly as described in the figure legends. Trabectedin was formulated at 0.0375 mg/mL in the water as described above. Trabectedin or vehicle was administered intravenously by tail vein injection in a final volume of 100 mL. rRp450 was diluted in PBS to 1.0 108 plaque-forming units (pfu)/mL and administered intratumorally in a final volume of 100 mL. PBS was administered intratumorally as the control for rRp450 in a final volume of 100 mL. In Vivo Efficacy Studies

When tumors reached a mean volume between 150 and 250 mm3, mice were randomized into four study groups depending on the experiment. The specific dosing schema for each experiment is described in the figure legends. Animals were followed until the animal reached endpoint criteria (including tumor volume >2,000 mm3, body weight loss >20%, unusual mouse behavior, lack of movement, or poor posture) or 60 days. Tumor size was measured using calipers thrice weekly, and tumor volume was calculated using the following formula: a b2 (p/6), where a is the length and b is the width. Mice were also weighed and observed three times per week for signs of endpoint condition. Mice that demonstrated signs of toxicity or


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reached endpoint criteria were humanely euthanized by CO2 asphyxiation and subjected to cervical dislocation as the secondary method of euthanasia.

their respective Ewing sarcoma cell cocultures. The Ewing sarcoma absorbance values where then normalized to the values of the uninfected Ewing sarcoma alone-treated wells.

Viral Replication

Biomark qPCR Array

Xenograft tumors from mice treated with liposome, Clodrosome, or trabectedin regimens described in the figure legends were harvested 3, 72, and 144 hr after infection. Tumors were homogenized and subjected to three cycles of freezing and thawing before 5–8 log serial dilution in 10% FBS DMEM and inoculation of a 90% confluent 12-well plate of Vero cells. Virus was applied for 2 hr before adding overlay media (1% carboxymethylcellulose [CMC], 1 MEM, 10% FBS) and incubating in a 37 C incubator for 2 days. Plates were stained in crystal violet for 20 min, washed in tap water, and dried overnight. Viral plaques are counted and multiplied by serial dilution to determine viral titer. Each graph is the accumulation of two to three experimental replicates.

Whole tumor lysates from Clodrosome/Liposome PBS/rRp450treated A673 xenografts described above were harvested at 3 hr, 5 days, and 25 days postinfection. F4/80+ tumor macrophages lysates were harvested from Clodrosome/Liposome PBS/rRp450treated A673 xenografts described above using a 44%/66% percoll RPMI gradient extraction of the buffy coat, followed by positive selection of F4/80+ tumor macrophages using antibody-conjugated magnetic beads. The stimulated BMDMs cultured alone and cocultured with Ewing sarcoma cells described above were harvested and lysed. With the assistance of the Ohio State University Genomics Core, RNA was extracted from these samples using an RNeasy Plus Mini Kit (Qiagen), diluted to a concentration of 10 ng/mL, and run on a Biomark HD qPCR array chip (Fluidigm) with a custom panel of gene primers designed by Fluidigm targeting genes we selected including housekeeping, HSV-1, and genes known to be differentially expressed in variously polarized macrophages. See the Delta Gene Assay Report in the Supplemental Information for a complete listing of genes tested and their amplicon sizes. Relative RNA expression values for each gene were normalized to actin expression for each treatment condition using the 2 DDCt method. See Tables S1, S2, and S3 for raw threshold cycle (Ct) data and normalization calculations for all of the genes tested.

Flow Cytometry

Splenocytes or single tumor cell suspensions were prepared as described previously.50 1 106 cells were blocked with 5% mouse Fc blocking reagent (2.4G2; BD Biosciences) in fluorescence-activated cell sorting (FACS) buffer (1% FBS and 1 mM EDTA in PBS) and stained with antibodies against CD206-fluorescein isothiocyanate (FITC) (C068C2), CD49b-PE (DX5), Ly6C-antigen-presenting cell (APC) (AL-21), CD11c-PerCP/Cy5.5 (N418), CD11b-Violet 421 (M1/70), F4/80-PE-Cy7 (BM8), and Ly-6G-APC-Cy7 (1A8) on ice for 30 min. Stained cells were washed with FACS buffer and fixed in 0.5% paraformaldehyde. Samples were acquired on a BD FACS LSR II (BD Biosciences), and cell infiltrate analysis was carried out using the FlowJo software, version 10.0.3 (Tree Star). All the staining antibodies were obtained from BioLegend except for anti-Ly6C (BD Biosciences). Coculture Cytotoxicity

Bone marrow-derived macrophages (BMDMs) were positively selected from athymic nude mouse bone marrow using F4/80+ antibodies conjugated to magnetic beads, then incubated in 20% FBS RPMI supplemented with 200 ng/mL macrophage-colony stimulating factor (M-CSF) for >5 days. BMDMs were then left unstimulated in 20% FBS RPMI or supplemented with 20 ng/mL IFNg, 20 ng/mL IFNg + 5 ng/mL LPS, 5 ng/mL LPS, 20 ng/mL IL-4, 20 ng/mL IL-10, or 20 ng/mL TGF-b for 48 hr. Two thousand A673 or TC71 Ewing sarcoma cells were plated in 96-well plates alone or directly cocultured with 200 cells/mL BMDM cultures in 10% FBS DMEM stimulated with the respective cytokines of the BMDMs for 2 hr. Cocultures were then infected with oHSVrRp450 at MOI 0.1 or 0 and incubated at 37 C for 6 days with additional cytokine stimulation to starting concentrations every 48 hr. Cell viability was determined using the CellTiter 96 (Promega) MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay kit. Cell viability was calculated by recording the 490 nm absorbance values and omitting the values of the infected BMDM cultures alone from

72


Statistical Analysis

Survival studies were analyzed using Mantel-Cox log rank test. Comparison of samples with normal distribution was analyzed using Student’s t test. Difference among group means was determined with ANOVA. Statistical tests were run on Microsoft Excel or GraphPad Prism v7.0. Significant differences in samples groups were determined by p < 0.05, whereas significant trends were determined by 0.05 < p < 0.15.

SUPPLEMENTAL INFORMATION Supplemental Information includes two figures, one Delta Gene Assay Report, and three tables, and can be found with this article online at https://doi.org/10.1016/j.omto.2018.10.001.

AUTHOR CONTRIBUTIONS Conceptualization, N.L.D., C.-Y.C., B.H., J.L.L., P.-Y.W., K.A.C., and T.P.C.; Methodology, N.L.D., C.-Y.C., M.A.C., K.A.C., W.F.G., and T.P.C.; Formal Analysis, N.L.D., C.-Y.C., B.H., M.A.C., and T.P.C.; Investigation, N.L.D., C.-Y.C., B.H., J.L.L., P.-Y.W., M.A.C., T.S., B.N., and R.S.; Resources, W.F.G. and T.P.C.; Data Curation, N.L.D., C.-Y.C., B.H., and M.A.C.; Writing – Original Draft, N.L.D. and T.P.C.; Writing – Review & Editing, N.L.D., C.-Y.C., B.H., and T.P.C.; Visualization, N.L.D., C.-Y.C., B.H., and M.A.C.; Supervision, C.-Y.C., K.A.C., and T.P.C.; Project Administration, T.P.C.; Funding Acquisition, N.L.D. and T.P.C.


CONFLICTS OF INTEREST None of the authors have any disclosures or conflicts of interest.

ACKNOWLEDGMENTS We thank Janssen Pharmaceuticals for providing trabectedin. We acknowledge The Ohio State University genomics core staff, particularly Xi Chen and Paolo Fadda, for their assistance in running the Biomark HD qPCR. The project was supported in part by National Cancer Institute (Bethesda, MD, USA) grant P30 CA016058, by Cancer Free Kids Pediatric Cancer Research Alliance, and by startup funds from the Research Institute at Nationwide Children’s Hospital. N.L.D. was supported by NIH HHS/USA grant F31 CA203252/CA/NCI, The Ohio State University Pelotonia Graduate Fellowship, Nationwide Children’s Hospital Student Research Award, and Alex’s Lemonade Stand Pediatric Oncology Student Training Fellowship.

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OMTO, Volume 11

Supplemental Information

Myelolytic Treatments Enhance Oncolytic Herpes Virotherapy in Models of Ewing Sarcoma by Modulating the Immune Microenvironment Nicholas L. Denton, Chun-Yu Chen, Brian Hutzen, Mark A. Currier, Thomas Scott, Brooke Nartker, Jennifer L. Leddon, Pin-Yi Wang, Rachelle Srinivas, Kevin A. Cassady, William F. Goins, and Timothy P. Cripe

Supplementary Figures

Fig. S1. Leukocyte flow cytometry gating. Flow cytometry gating strategy for individual leukocyte subpopulations in tumor implanted athymic nude mice splenocytes and Ewing sarcoma xenografts.

Fig. S2. Inhibition of TGFβ signaling inhibition alone does not enhance oncolytic virus efficacy in A673. (A) We inhibited TGFβ signaling in A673 xenografts using thrice weekly i.p. A8301 prior to i.t. rRp450 treatments on days 2 and 4. (B) We measured A673 flank xenografts until tumors reached an end point volume of 2,000 mm3. Statistical analysis of survival curves was performed using Mantel-Cox; we did not statistically significant differences between virotherapy alone or combined with A8301.

The following pages contain the information from Fluidigm regarding the primers used for the Biomark assay.

Delta Gene Assay Report

Panel Name

7690_DGP_17.T1

Plate ID

7690DGP17T1_P01

A1 Assay Name Gene Symbol

ACTB_80796_i2 Actb

Entrez Gene ID

Assay ID 11461

GEP00080796 Organism Mus musculus

Official Full Name actin, beta Related IDs

MGI:MGI:87904; Ensembl:ENSMUSG00000029580; Vega:OTTMUSG00000035960

Also known as GO Function

Actx; beta-actin; E430023M04Rik ATP binding; RNA polymerase II core promoter proximal region sequence-specific DNA binding; RNA polymerase II distal enhancer sequence-specific DNA binding; Tat protein binding; identical protein binding; kinesin binding; nitric-oxide synthase binding; nucleosomal DNA binding; nucleotide binding; protein binding; protein kinase binding; structural constituent of postsynaptic actin cytoskeleton Go Process ATP-dependent chromatin remodeling; axonogenesis; cellular response to electrical stimulus; platelet aggregation; postsynaptic actin cytoskeleton organization Go Component NuA4 histone acetyltransferase complex; axon; blood microparticle; cortical cytoskeleton; cytoplasm; cytoplasmic ribonucleoprotein granule; cytoskeleton; cytosol; extracellular exosome; extracellular space; focal adhesion; intracellular ribonucleoprotein complex; membrane; membrane raft; myelin sheath; nuclear chromatin; podosome; postsynaptic density; protein complex; stress fiber; vesicle Gene Isoforms NM_007393. Blast Isoform Hits NM_007393 Amplicon Length 82 Exon 3-4 CDS Full

B1 Assay Name Gene Symbol

ADGRD1_80794_i8 Adgrd1

Entrez Gene ID

Assay ID 243277


Official Full Name adhesion G protein-coupled receptor D1 Related IDs


Also known as GO Function Go Process

Gpr133; E230012M21Rik G-protein coupled receptor activity; transmembrane signaling receptor activity G-protein coupled receptor signaling pathway; cell surface receptor signaling pathway; positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway Go Component integral component of membrane; membrane; plasma membrane Gene Isoforms NM_001081342.; NM_001347486. Blast Isoform Hits NM_001347486; NM_001081342 Amplicon Length 79 Exon 9-10 CDS Full

7690_DGP_17.T1

1/64

C1 Assay Name Gene Symbol

ARG1_80804_i0 Arg1

Entrez Gene ID

Assay ID 11846


Official Full Name arginase, liver Related IDs

MGI:MGI:88070; Ensembl:ENSMUSG00000019987


AI; PGIF; Arg-1; AI256583 arginase activity; arginase activity; hydrolase activity; hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines; manganese ion binding; metal ion binding Go Process arginine catabolic process to ornithine; arginine metabolic process; collagen biosynthetic process; positive regulation of endothelial cell proliferation; protein homotrimerization; regulation of L-arginine import; urea cycle Go Component cytoplasm; extracellular exosome; extracellular space; mitochondrial outer membrane; neuron projection; neuronal cell body; nucleus Gene Isoforms NM_007482. Blast Isoform Hits NM_007482 Amplicon Length 81 Exon 1-2 CDS Full

D1 Assay Name Gene Symbol

ATG12_80886_i2 Atg12

Entrez Gene ID

Assay ID 67526


Official Full Name autophagy related 12 Related IDs



Apg12l; Atg12l; 4931423H11Rik; A330058M13Rik Atg8 ligase activity; protein binding C-terminal protein lipidation; autophagosome assembly; autophagy; autophagy; immune system process; innate immune response; mitophagy; nucleophagy Go Component Atg12-Atg5-Atg16 complex; cytoplasm; membrane; membrane; pre-autophagosomal structure membrane; protein complex Gene Isoforms NM_026217.N Blast Isoform Hits NM_026217 Amplicon Length 84 Exon 3-4 CDS Full

7690_DGP_17.T1

2/64

E1 Assay Name Gene Symbol

CCl1_80807_i0 Ccl1

Entrez Gene ID

Assay ID 20290


Official Full Name chemokine (C-C motif) ligand 1 Related IDs



I-309; Scya1; Tca-3; BF534335 CCR chemokine receptor binding; chemokine activity; chemokine activity; cytokine activity; protein binding G-protein coupled receptor signaling pathway; cellular response to interferon-gamma; cellular response to interleukin-1; cellular response to tumor necrosis factor; chemokine-mediated signaling pathway; chemotaxis; immune response; inflammatory response; lymphocyte chemotaxis; monocyte chemotaxis; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; positive regulation of cytosolic calcium ion concentration; positive regulation of monocyte chemotaxis

Go Component Gene Isoforms Blast Isoform Hits Amplicon Length

extracellular region; extracellular space; extracellular space NM_011329. NM_011329 68 Exon 1-2 CDS

Full

F1 Assay Name Gene Symbol

CCL12_80848_i1 Ccl12

Entrez Gene ID

Assay ID 20293





MCP-5; Scya12 CCR2 chemokine receptor binding; chemokine activity; cytokine activity G-protein coupled receptor signaling pathway; MAPK cascade; angiogenesis; astrocyte cell migration; cellular response to interferon-gamma; cellular response to interleukin-1; cellular response to organic cyclic compound; cellular response to tumor necrosis factor; chemokine-mediated signaling pathway; chemotaxis; cytokinemediated signaling pathway; cytoskeleton organization; immune response; inflammatory response; inflammatory response; lipopolysaccharide-mediated signaling pathway; lymphocyte chemotaxis; macrophage chemotaxis; monocyte chemotaxis; monocyte chemotaxis; negative regulation of glial cell apoptotic process; negative regulation of leukocyte proliferation; negative regulation of natural killer cell chemotaxis; negative regulation of neuron apoptotic process; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; positive regulation of calcium ion import; positive regulation of leukocyte migration; protein kinase B signaling; regulation of cell shape


extracellular region; extracellular space NM_011331.N NM_011331 98 Exon 2-3

7690_DGP_17.T1

CDS

Full

3/64

G1 Assay Name Gene Symbol

CCL17_79716_i1 Ccl17

Entrez Gene ID

Assay ID 20295





Tarc; Abcd-2; Scya17; Scya17l CCR chemokine receptor binding; CCR4 chemokine receptor binding; chemokine activity; cytokine activity G-protein coupled receptor signaling pathway; cellular defense response; cellular response to interferon-gamma; cellular response to interleukin-1; cellular response to tumor necrosis factor; chemokine-mediated signaling pathway; chemotaxis; inflammatory response; lymphocyte chemotaxis; monocyte chemotaxis; negative regulation of myoblast differentiation; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; signal transduction


extracellular space NM_011332. NM_011332 79

7690_DGP_17.T1

Exon

2-3

CDS

Full

4/64

H1 Assay Name Gene Symbol

CCL2_36445_i1 Ccl2

Entrez Gene ID

Assay ID 20296

GEA00036445 Organism Mus musculus




JE; HC11; MCAF; MCP1; MCP-1; Scya2; Sigje; SMC-CF; AI323594 CCR2 chemokine receptor binding; CCR2 chemokine receptor binding; G-protein coupled receptor binding; chemokine activity; chemokine activity; cytokine activity; heparin binding; protein binding G-protein coupled receptor signaling pathway; angiogenesis; cellular calcium ion homeostasis; cellular response to interferon-gamma; cellular response to interleukin-1; cellular response to lipopolysaccharide; cellular response to tumor necrosis factor; chemokine-mediated signaling pathway; chemokine-mediated signaling pathway; chemotaxis; cytokine-mediated signaling pathway; cytoskeleton organization; eosinophil chemotaxis; glial cell migration; helper T cell extravasation; immune response; inflammatory response; leukocyte migration involved in inflammatory response; lymphocyte chemotaxis; lymphocyte chemotaxis; macrophage chemotaxis; monocyte homeostasis; negative regulation of angiogenesis; neutrophil chemotaxis; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; positive regulation of T cell activation; positive regulation of apoptotic cell clearance; positive regulation of cell adhesion; positive regulation of cell-cell adhesion; positive regulation of cellular extravasation; positive regulation of collagen biosynthetic process; positive regulation of endothelial cell proliferation; positive regulation of immune complex clearance by monocytes and macrophages; positive regulation of leukocyte mediated cytotoxicity; positive regulation of leukocyte migration; positive regulation of macrophage chemotaxis; positive regulation of macrophage chemotaxis; positive regulation of monocyte chemotaxis; positive regulation of monocyte chemotaxis; positive regulation of nitric-oxide synthase biosynthetic process; positive regulation of protein targeting to membrane; positive regulation of synaptic transmission; positive regulation of tumor necrosis factor production; positive regulation of wound healing; regulation of cell shape; regulation of vascular endothelial growth factor production; response to heat; response to wounding; transforming growth factor beta receptor signaling pathway; vascular endothelial growth factor receptor signaling pathway C-fiber; axon terminus; cytoplasm; dendrite; endocytic vesicle; extracellular region; extracellular space; extracellular space; neuronal cell body; perikaryon; perinuclear region of cytoplasm; rough endoplasmic reticulum; synapse

Go Process

Go Component

Gene Isoforms NM_011333. Blast Isoform Hits NM_011333 Amplicon Length 74

7690_DGP_17.T1

Exon

2-3

CDS

Full

5/64


CCL20_80806_i0 Ccl20

Entrez Gene ID

Assay ID 20297





CKb4; LARC; ST38; MIP3A; MIP-3A; Scya20; MIP-3[a]; exodus-1 CCR6 chemokine receptor binding; CCR6 chemokine receptor binding; chemokine activity; chemokine activity; cytokine activity; protein binding G-protein coupled receptor signaling pathway; T cell migration; calcium-mediated signaling using intracellular calcium source; cell chemotaxis; cellular response to interferon-gamma; cellular response to interleukin-1; cellular response to tumor necrosis factor; chemokine-mediated signaling pathway; chemotaxis; chemotaxis; immune response; inflammatory response; lymphocyte chemotaxis; monocyte chemotaxis; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; positive regulation of T cell migration; positive regulation of interleukin-1 alpha biosynthetic process; positive regulation of nitric-oxide synthase biosynthetic process; regulation of T cell cytokine production; regulation of T-helper 17 cell differentiation; thymocyte migration

Go Process


extracellular region; extracellular space; extracellular space NM_016960.; NM_001159738. NM_001159738 80 Exon 1-2 CDS

Full


CCL22_80809_i0 Ccl22

Entrez Gene ID

Assay ID 20299





MDC; DCBCK; ABCD-1; Scya22 CCR chemokine receptor binding; chemokine activity; cytokine activity G-protein coupled receptor signaling pathway; cell chemotaxis; cellular response to interferon-gamma; cellular response to interleukin-1; cellular response to tumor necrosis factor; chemokine-mediated signaling pathway; chemotaxis; immune response; inflammatory response; lymphocyte chemotaxis; monocyte chemotaxis; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity Go Component extracellular region; extracellular space Gene Isoforms NM_009137. Blast Isoform Hits NM_009137 Amplicon Length 74 Exon 1-2 CDS Full

7690_DGP_17.T1

6/64


CCL3_80843_i0 Ccl3

Entrez Gene ID

Assay ID 20302





Mip1a; Scya3; G0S19-1; AI323804; MIP1-(a); LD78alpha; MIP-1alpha; MIP1-alpha CCR chemokine receptor binding; chemokine activity; chemokine activity; cytokine activity; protein binding G-protein coupled receptor signaling pathway; astrocyte cell migration; cellular response to interferon-gamma; cellular response to interleukin-1; cellular response to tumor necrosis factor; chemokine-mediated signaling pathway; chemotaxis; immune response; inflammatory response; leukocyte chemotaxis; lymphocyte chemotaxis; macrophage chemotaxis; monocyte chemotaxis; neutrophil chemotaxis; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; positive regulation of cytosolic calcium ion concentration; positive regulation of inflammatory response; positive regulation of interleukin-1 beta secretion; positive regulation of neuron apoptotic process; positive regulation of osteoclast differentiation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of tumor necrosis factor production; regulation of cell shape Go Component extracellular region; extracellular space Gene Isoforms NM_011337. Blast Isoform Hits NM_011337 Amplicon Length 88 Exon 1-2 CDS Full


CCL4_80846_i0 Ccl4

Entrez Gene ID

Assay ID 20303





Act-2; Mip1b; Scya4; MIP-1B; AT744.1 CCR chemokine receptor binding; CCR1 chemokine receptor binding; CCR5 chemokine receptor binding; chemokine activity; chemokine activity; cytokine activity; identical protein binding; protein binding G-protein coupled receptor signaling pathway; cellular response to drug; cellular response to interferon-gamma; cellular response to interleukin-1; cellular response to tumor necrosis factor; chemokine-mediated signaling pathway; chemotaxis; immune response; inflammatory response; inflammatory response; leukocyte chemotaxis; lymphocyte chemotaxis; monocyte chemotaxis; negative regulation by host of viral transcription; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; positive regulation of calcium ion transport; positive regulation of calcium-mediated signaling; positive regulation of natural killer cell chemotaxis; positive regulation of tumor necrosis factor production; positive regulation of vascular permeability; response to toxic substance

Go Process


7690_DGP_17.T1

extracellular region; extracellular space NM_013652. NM_013652 125 Exon 1-2

CDS

Full

7/64


CCL5_80845_i1 Ccl5

Entrez Gene ID

Assay ID 20304





SISd; Scya5; RANTES; TCP228; MuRantes CCR1 chemokine receptor binding; CCR1 chemokine receptor binding; CCR4 chemokine receptor binding; CCR5 chemokine receptor binding; chemoattractant activity; chemokine activity; chemokine activity; chemokine receptor antagonist activity; chemokine receptor binding; cytokine activity; heparin binding; phosphatidylinositol phospholipase C activity; phospholipase activator activity; protein homodimerization activity; protein kinase activity; protein self-association; receptor signaling protein tyrosine kinase activator activity

Go Process

G-protein coupled receptor signaling pathway; G-protein coupled receptor signaling pathway; MAPK cascade; Thelper 1 cell diapedesis; activation of phospholipase D activity; calcium ion transport; cell-cell signaling; cellular calcium ion homeostasis; cellular protein complex assembly; cellular response to interferon-gamma; cellular response to interleukin-1; cellular response to organic cyclic compound; cellular response to tumor necrosis factor; chemokine-mediated signaling pathway; chemokine-mediated signaling pathway; chemotaxis; eosinophil chemotaxis; exocytosis; immune response; inflammatory response; inflammatory response; leukocyte cell-cell adhesion; lipopolysaccharide-mediated signaling pathway; lymphocyte chemotaxis; lymphocyte chemotaxis; negative regulation by host of viral transcription; negative regulation of G-protein coupled receptor protein signaling pathway; negative regulation of T cell apoptotic process; negative regulation of cell death; negative regulation of macrophage apoptotic process; negative regulation of neuron death; negative regulation of viral genome replication; neutrophil activation; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; positive regulation of T cell apoptotic process; positive regulation of T cell chemotaxis; positive regulation of T cell chemotaxis; positive regulation of T cell migration; positive regulation of T cell proliferation; positive regulation of angiogenesis; positive regulation of calcium ion transport; positive regulation of cell adhesion; positive regulation of cell migration; positive regulation of cell-cell adhesion mediated by integrin; positive regulation of cellular biosynthetic process; positive regulation of chemokine (C-X-C motif) ligand 2 production; positive regulation of defense response to virus by host; positive regulation of epithelial cell proliferation; positive regulation of fever generation; positive regulation of gene expression; positive regulation of homotypic cell-cell adhesion; positive regulation of macrophage chemotaxis; positive regulation of mast cell chemotaxis; positive regulation of monocyte chemotaxis; positive regulation of monocyte chemotaxis; positive regulation of natural killer cell chemotaxis; positive regulation of neuron differentiation; positive regulation of osteoclast differentiation; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of phosphorylation; positive regulation of smooth muscle cell migration; positive regulation of smooth muscle cell proliferation; positive regulation of tyrosine phosphorylation of STAT protein; protein kinase B signaling; protein tetramerization; pseudopodium assembly; regulation of T cell activation; regulation of insulin secretion; regulation of neuron death; response to cytokine; response to interferon-gamma; response to toxic substance; response to tumor necrosis factor; response to virus Go Component cytoplasm; extracellular region; extracellular space; extracellular space Gene Isoforms NM_013653. Blast Isoform Hits NM_013653 Amplicon Length 80 Exon 2-3 CDS Full

7690_DGP_17.T1

8/64


CCL7_78485_i0 Ccl7

Entrez Gene ID

Assay ID 20306





fic; marc; mcp3; MCP-3; Scya7 CCR2 chemokine receptor binding; chemokine activity; cytokine activity; heparin binding G-protein coupled receptor signaling pathway; cellular response to ethanol; cellular response to interferongamma; cellular response to interleukin-1; cellular response to tumor necrosis factor; chemokine-mediated signaling pathway; chemotaxis; immune response; inflammatory response; lymphocyte chemotaxis; monocyte chemotaxis; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity


extracellular region; extracellular space NM_013654. NM_013654 86 Exon 1-2

CDS

CCL9_80847_i1 Ccl9

Assay ID 20308

Full


Entrez Gene ID





CCF18; MRP-2; Scya9; Scya10 CCR chemokine receptor binding; chemokine activity; cytokine activity G-protein coupled receptor signaling pathway; cellular response to interferon-gamma; cellular response to interleukin-1; cellular response to tumor necrosis factor; chemokine-mediated signaling pathway; chemotaxis; immune response; inflammatory response; lymphocyte chemotaxis; monocyte chemotaxis; negative regulation of myoblast differentiation; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity


extracellular region; extracellular space NM_011338.N NM_011338 70 Exon 2-3

7690_DGP_17.T1

CDS

Full

9/64


CCND2_80885_i1 Ccnd2

Entrez Gene ID

Assay ID 12444


Official Full Name cyclin D2 Related IDs



cD2; Vin1; Vin-1; C86853; AI256817; BF642806; 2600016F06Rik protein binding; protein kinase binding G1/S transition of mitotic cell cycle; adult locomotory behavior; cell cycle; cell division; cellular response to X-ray; long-term memory; negative regulation of apoptotic process; positive regulation of G1/S transition of mitotic cell cycle; positive regulation of cell proliferation; positive regulation of cyclin-dependent protein serine/threonine kinase activity; positive regulation of epithelial cell proliferation; positive regulation of protein phosphorylation; regulation of cell cycle

Go Component

chromatin; cyclin D2-CDK4 complex; cyclin-dependent protein kinase holoenzyme complex; cytoplasm; cytosol; membrane; nuclear membrane; nucleolus; nucleoplasm; nucleus; nucleus Gene Isoforms NM_009829. Blast Isoform Hits NM_009829 Amplicon Length 90 Exon 2-3 CDS Full


CCR1_80840_i0 Ccr1

Entrez Gene ID

Assay ID 12768


Official Full Name chemokine (C-C motif) receptor 1 Related IDs



Cmkbr1; Mip-1a-R C-C chemokine binding; C-C chemokine receptor activity; C-C chemokine receptor activity; G-protein coupled receptor activity; chemokine (C-C motif) ligand 5 binding; chemokine (C-C motif) ligand 7 binding; chemokine receptor activity; phosphatidylinositol phospholipase C activity; protein binding; signal transducer activity

Go Process

G-protein coupled receptor signaling pathway; calcium ion transport; cell-cell signaling; cellular calcium ion homeostasis; chemokine-mediated signaling pathway; chemotaxis; exocytosis; immune response; inflammatory response; leukocyte chemotaxis; leukocyte chemotaxis; myeloid cell differentiation; negative regulation of bone mineralization; negative regulation of gene expression; negative regulation of innate immune response; positive regulation of ERK1 and ERK2 cascade; positive regulation of calcium ion transport; positive regulation of cell migration; positive regulation of cytosolic calcium ion concentration; positive regulation of monocyte chemotaxis; positive regulation of osteoclast differentiation; signal transduction Go Component external side of plasma membrane; integral component of membrane; membrane; neuronal cell body; plasma membrane Gene Isoforms NM_009912.N Blast Isoform Hits NM_009912 Amplicon Length 115 Exon 1-2 CDS None

7690_DGP_17.T1

10/64


CD274_80865_i1 Cd274

Entrez Gene ID

Assay ID 60533


Official Full Name CD274 antigen Related IDs



B7h1; Pdl1; Pdcd1l1; Pdcd1lg1; A530045L16Rik protein binding T cell costimulation; cell surface receptor signaling pathway; immune response; negative regulation of T cell proliferation; negative regulation of activated T cell proliferation; negative regulation of interferon-gamma production; negative regulation of interleukin-10 production; negative regulation of tumor necrosis factor superfamily cytokine production; positive regulation of T cell proliferation; positive regulation of activated CD8positive, alpha-beta T cell apoptotic process; positive regulation of cell migration; positive regulation of interleukin10 secretion; response to cytokine; signal transduction; toxin transport Go Component cell surface; external side of plasma membrane; extracellular exosome; integral component of membrane; membrane; plasma membrane Gene Isoforms NM_021893. Blast Isoform Hits NM_021893 Amplicon Length 80 Exon 2-3 CDS Full


CD40_79724_i0 Cd40

Entrez Gene ID

Assay ID 21939





IGM; p50; Bp50; GP39; IMD3; TRAP; HIGM1; T-BAM; Tnfrsf5; AI326936 antigen binding; enzyme binding; protein binding; protein domain specific binding; receptor activity; tumor necrosis factor-activated receptor activity; ubiquitin protein ligase binding B cell activation; apoptotic signaling pathway; cellular calcium ion homeostasis; cellular calcium ion homeostasis; defense response to protozoan; defense response to virus; immune response-regulating cell surface receptor signaling pathway; immune system process; inflammatory response; inflammatory response; positive regulation of B cell proliferation; positive regulation of B cell proliferation; positive regulation of GTPase activity; positive regulation of MAP kinase activity; positive regulation of NF-kappaB transcription factor activity; positive regulation of endothelial cell apoptotic process; positive regulation of interleukin-12 production; positive regulation of isotype switching to IgG isotypes; positive regulation of protein kinase C signaling; positive regulation of protein phosphorylation; positive regulation of transcription from RNA polymerase II promoter; protein kinase B signaling; regulation of apoptotic process; regulation of immune response; regulation of immunoglobulin secretion; response to lipopolysaccharide

Go Process

Go Component

CD40 receptor complex; cell surface; cell surface; cytoplasm; external side of plasma membrane; extracellular exosome; extracellular region; extracellular space; integral component of membrane; intracellular membranebounded organelle; membrane; neuronal cell body; plasma membrane; varicosity

Gene Isoforms NR_027852.; NM_011611.; NM_170704.; NM_170703.; NM_170702. Blast Isoform Hits NM_170702; NM_011611; NR_027852; NM_170704; NM_170703 Amplicon Length 74 Exon 1-2 CDS Full

7690_DGP_17.T1

11/64


CD52_80857_i0 Cd52

Entrez Gene ID

Assay ID 23833




Also known as GO Function Go Process Go Component Gene Isoforms Blast Isoform Hits Amplicon Length

B7; MB7; CLS1; B7-Ag; AI463198; CAMPATH-1

anchored component of membrane; membrane; plasma membrane; sperm midpiece NM_013706.N NM_013706 79 Exon 1-2 CDS Full


CD80_80805_i3 Cd80

Entrez Gene ID

Assay ID 12519





B71; Ly53; TSA1; Cd28l; Ly-53; MIC17 protein binding T cell costimulation; cellular response to lipopolysaccharide; positive regulation of T cell proliferation; positive regulation of T cell proliferation; positive regulation of alpha-beta T cell proliferation; positive regulation of peptidyl -tyrosine phosphorylation

Go Component

cell surface; external side of plasma membrane; integral component of membrane; membrane; protein complex involved in cell adhesion Gene Isoforms NM_009855. Blast Isoform Hits NM_009855 Amplicon Length 85 Exon 4-5 CDS Full

7690_DGP_17.T1

12/64


CD86_13426_i1 Cd86

Entrez Gene ID

Assay ID 12524





B7; B70; MB7; B7-2; B7.2; CLS1; Ly58; ETC-1; Ly-58; MB7-2; Cd28l2; TS/A-2 receptor binding B cell activation; adaptive immune response; cellular response to lipopolysaccharide; defense response to virus; immune system process; negative regulation of T cell anergy; positive regulation of T cell proliferation; positive regulation of T cell proliferation; positive regulation of activated T cell proliferation; toll-like receptor 3 signaling pathway; toll-like receptor signaling pathway Go Component cell surface; external side of plasma membrane; extracellular exosome; integral component of membrane; intracellular membrane-bounded organelle; membrane; plasma membrane Gene Isoforms NM_019388. Blast Isoform Hits NM_019388 Amplicon Length 83 Exon 2-3 CDS Full


CHIL3_80812_i7 Chil3

Entrez Gene ID

Assay ID 12655


Official Full Name chitinase-like 3 Related IDs



Ym1; ECF-L; Chi3l3; AI505981 beta-N-acetylhexosaminidase activity; carbohydrate binding; chitin binding; chitinase activity; hydrolase activity; hydrolase activity, acting on glycosyl bonds Go Process carbohydrate metabolic process; inflammatory response; metabolic process; polysaccharide catabolic process Go Component cytoplasm; cytoplasmic vesicle; endoplasmic reticulum; extracellular region; nucleus Gene Isoforms NM_009892. Blast Isoform Hits NM_009892 Amplicon Length 84 Exon 8-9 CDS Full

7690_DGP_17.T1

13/64


CHUK_80889_i17 Chuk

Entrez Gene ID

Assay ID 12675


Official Full Name conserved helix-loop-helix ubiquitous kinase Related IDs



IKK1; Ikka; Chuk1; Fbx24; IKBKA; Fbxo24; NFKBIKA; AI256658 ATP binding; IkappaB kinase activity; IkappaB kinase activity; kinase activity; nucleotide binding; protein binding; protein heterodimerization activity; protein homodimerization activity; protein kinase activity; protein kinase activity; protein serine/threonine kinase activity; scaffold protein binding; signal transducer, downstream of receptor, with serine/threonine kinase activity; transferase activity I-kappaB kinase/NF-kappaB signaling; I-kappaB phosphorylation; NIK/NF-kappaB signaling; Rho protein signal transduction; cellular response to cadmium ion; cellular response to reactive oxygen species; cellular response to tumor necrosis factor; cellular response to virus; cellular response to virus; defense response to virus; inflammatory response; innate immune response; lactation; lactation; mammary gland alveolus development; mammary gland alveolus development; mammary gland epithelial cell proliferation; mammary gland epithelial cell proliferation; morphogenesis of an epithelial sheet; odontogenesis of dentin-containing tooth; osteoclast differentiation; osteoclast differentiation; peptidyl-serine phosphorylation; phosphorylation; positive regulation of I -kappaB kinase/NF-kappaB signaling; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of NF-kappaB transcription factor activity; positive regulation of interferon-alpha secretion; positive regulation of interferon-alpha secretion; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNAtemplated; protein phosphorylation; response to lipopolysaccharide; response to muscle stretch; response to organic substance; striated muscle cell differentiation; tumor necrosis factor-mediated signaling pathway

Go Process

Go Component

CD40 receptor complex; IkappaB kinase complex; IkappaB kinase complex; cytoplasm; cytoplasmic side of plasma membrane; cytosol; intracellular membrane-bounded organelle; nucleoplasm; nucleus Gene Isoforms NM_007700.N; NM_001162410.N Blast Isoform Hits NM_001162410; NM_007700 Amplicon Length 78 Exon 18-19 CDS Full


CMKLR1_80853_i1 Cmklr1

Entrez Gene ID

Assay ID 14747


Official Full Name chemokine-like receptor 1 Related IDs



DEZ; Gpcr27; ChemR23; mcmklr1 G-protein coupled receptor activity; signal transducer activity G-protein coupled receptor signaling pathway; chemotaxis; negative regulation of NF-kappaB transcription factor activity; negative regulation of interleukin-12 production; positive regulation of fat cell differentiation; positive regulation of macrophage chemotaxis; regulation of calcium-mediated signaling; signal transduction


integral component of membrane; membrane; plasma membrane NM_008153.N NM_008153 97 Exon 2-3 CDS

7690_DGP_17.T1

Partial

14/64


CSF1R_80858_i17 Csf1r

Entrez Gene ID

Assay ID 12978


Official Full Name colony stimulating factor 1 receptor Related IDs



Fms; Fim2; CD115; Csfmr; Fim-2; CSF-1R; M-CSFR; M-CSF-R; AI323359 ATP binding; cytokine binding; cytokine binding; cytokine binding; kinase activity; macrophage colony-stimulating factor receptor activity; macrophage colony-stimulating factor receptor activity; macrophage colony-stimulating factor receptor activity; nucleotide binding; protein binding; protein homodimerization activity; protein kinase activity; protein phosphatase binding; protein tyrosine kinase activity; transferase activity; transmembrane receptor protein tyrosine kinase activity

Go Process

axon guidance; cell proliferation; cell-cell junction maintenance; cellular response to cytokine stimulus; cellular response to macrophage colony-stimulating factor stimulus; cellular response to macrophage colony-stimulating factor stimulus; cytokine-mediated signaling pathway; forebrain neuron differentiation; hemopoiesis; immune system process; inflammatory response; innate immune response; macrophage colony-stimulating factor signaling pathway; negative regulation of apoptotic process; negative regulation of cell proliferation; olfactory bulb development; osteoclast differentiation; peptidyl-tyrosine phosphorylation; peptidyl-tyrosine phosphorylation; phosphatidylinositol metabolic process; phosphatidylinositol-mediated signaling; phosphorylation; positive regulation of ERK1 and ERK2 cascade; positive regulation of cell migration; positive regulation of cell motility; positive regulation of cell proliferation; positive regulation of cell proliferation; positive regulation of chemokine secretion; positive regulation of osteoclast differentiation; positive regulation of protein phosphorylation; positive regulation of protein serine/threonine kinase activity; positive regulation of protein tyrosine kinase activity; protein autophosphorylation; protein autophosphorylation; protein phosphorylation; regulation of actin cytoskeleton reorganization; regulation of bone resorption; regulation of cell shape; regulation of cell shape; ruffle organization; transmembrane receptor protein tyrosine kinase signaling pathway; transmembrane receptor protein tyrosine kinase signaling pathway Go Component CSF1-CSF1R complex; cell surface; integral component of membrane; intracellular membrane-bounded organelle; membrane; nucleoplasm; plasma membrane; plasma membrane Gene Isoforms NM_001037859. Blast Isoform Hits NM_001037859 Amplicon Length 82 Exon 18-19 CDS Full

7690_DGP_17.T1

15/64


CTLA4_80888_i0 Ctla4

Entrez Gene ID

Assay ID 12477


Official Full Name cytotoxic T-lymphocyte-associated protein 4 Related IDs



Cd152; Ly-56; Ctla-4

Go Component

B cell receptor signaling pathway; adaptive immune response; cellular response to DNA damage stimulus; immune response; immune system process; negative regulation of B cell proliferation; negative regulation of T cell proliferation; negative regulation of immune response; negative regulation of regulatory T cell differentiation; positive regulation of apoptotic process Golgi apparatus; clathrin-coated endocytic vesicle; external side of plasma membrane; external side of plasma membrane; integral component of membrane; membrane; perinuclear region of cytoplasm; plasma membrane; protein complex involved in cell adhesion

Gene Isoforms NM_009843.; NM_001281976. Blast Isoform Hits NM_009843; NM_001281976 Amplicon Length 81 Exon

1-2

CDS

Full


CXCL1_78479_i1 Cxcl1

Entrez Gene ID

Assay ID 14825


Official Full Name chemokine (C-X-C motif) ligand 1 Related IDs



KC; Fsp; N51; gro; Gro1; Mgsa; Scyb1 CXCR chemokine receptor binding; chemokine activity; chemokine activity; cytokine activity; growth factor activity G-protein coupled receptor signaling pathway; acute inflammatory response; chemokine-mediated signaling pathway; chemotaxis; defense response; immune response; inflammatory response; neutrophil chemotaxis; positive regulation of cytosolic calcium ion concentration; positive regulation of hematopoietic stem cell proliferation; positive regulation of neutrophil chemotaxis; positive regulation of neutrophil mediated killing of fungus; positive regulation of potassium ion transport; positive regulation of sodium ion transport; positive regulation of superoxide anion generation; response to lipopolysaccharide; response to molecule of bacterial origin Go Component extracellular region; extracellular space; extracellular space Gene Isoforms NM_008176. Blast Isoform Hits NM_008176 Amplicon Length 138 Exon 2-3 CDS Full

7690_DGP_17.T1

16/64



Entrez Gene ID

Assay ID 15945





C7; IP10; CRG-2; INP10; IP-10; Ifi10; mob-1; Scyb10; gIP-10 CXCR3 chemokine receptor binding; CXCR3 chemokine receptor binding; chemokine activity; chemokine activity; cytokine activity; heparin binding G-protein coupled receptor signaling pathway; G-protein coupled receptor signaling pathway; T cell chemotaxis; T cell chemotaxis; cellular response to lipopolysaccharide; chemokine-mediated signaling pathway; chemokinemediated signaling pathway; chemotaxis; defense response; defense response to virus; endothelial cell activation; immune response; immune response; inflammatory response; negative regulation of angiogenesis; negative regulation of myoblast differentiation; negative regulation of myoblast fusion; positive regulation of T cell migration; positive regulation of cAMP metabolic process; positive regulation of cAMP-mediated signaling; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of leukocyte chemotaxis; positive regulation of leukocyte chemotaxis; positive regulation of monocyte chemotaxis; positive regulation of release of sequestered calcium ion into cytosol; regulation of T cell chemotaxis; regulation of cell proliferation; regulation of cell proliferation; regulation of endothelial tube morphogenesis; response to lipopolysaccharide

Go Process


external side of plasma membrane; extracellular region; extracellular space; extracellular space NM_021274. NM_021274 103 Exon 2-3 CDS Full



Entrez Gene ID

Assay ID 56066





Ip9; H174; Itac; b-R1; Cxc11; I-tac; Scyb11; Scyb9b; betaR1

7690_DGP_17.T1

NM_019494.N; NR_038116.N NR_038116 85 Exon

1-2

CDS

None

17/64



Entrez Gene ID

Assay ID 55985





BLC; Angie; BCA-1; BLR1L; ANGIE2; Scyb13; 4631412M08Rik CCR10 chemokine receptor binding; CXCR3 chemokine receptor binding; CXCR5 chemokine receptor binding; CXCR5 chemokine receptor binding; chemokine activity; chemokine activity; cytokine activity; fibroblast growth factor binding; heparin binding; protein heterodimerization activity; receptor agonist activity

Go Process

B cell chemotaxis; B cell chemotaxis; B cell chemotaxis across high endothelial venule; G-protein coupled receptor signaling pathway; activation of GTPase activity; cell surface receptor signaling pathway; cell-cell signaling; chemokine-mediated signaling pathway; chemokine-mediated signaling pathway; chemotaxis; defense response; defense response to bacterium; endothelial cell chemotaxis to fibroblast growth factor; immune response; inflammatory response; lymph node development; lymph node development; lymphocyte chemotaxis across high endothelial venule; negative regulation of endothelial cell chemotaxis to fibroblast growth factor; positive regulation of T cell chemotaxis; positive regulation of cell-cell adhesion mediated by integrin; positive regulation of cytosolic calcium ion concentration; positive regulation of integrin activation; positive regulation of leukocyte chemotaxis; regulation of cell proliferation; response to lipopolysaccharide Go Component extracellular region; extracellular space Gene Isoforms NM_018866.N Blast Isoform Hits NM_018866 Amplicon Length 80 Exon 3-4 CDS Full



Entrez Gene ID

Assay ID 66102





SR-PSOX; Zmynd15; AV290116; BB024863; CXCL16v1; CXCL16v2; b2b498Clo; 0910001K24Rik chemokine activity; chemokine activity; chemokine receptor binding; cytokine activity; low-density lipoprotein receptor activity; scavenger receptor activity T cell chemotaxis; cellular response to lipopolysaccharide; chemotaxis; lymphocyte chemotaxis; positive regulation of cell growth; positive regulation of cell migration; positive regulation of cell migration; receptor-mediated endocytosis; response to cytokine; response to interferon-gamma; response to tumor necrosis factor

Go Process


7690_DGP_17.T1

extracellular space; extracellular space; integral component of membrane; membrane NM_023158. NM_023158 69 Exon 3-4 CDS Full

18/64



Entrez Gene ID

Assay ID 20310





GROb; Gro2; Mip2; Scyb; MIP-2; Scyb2; MIP-2a; Mgsa-b; CINC-2a CXCR chemokine receptor binding; chemokine activity; chemokine activity; cytokine activity G-protein coupled receptor signaling pathway; chemokine-mediated signaling pathway; chemotaxis; defense response; immune response; inflammatory response; leukocyte chemotaxis; neuron death; neutrophil chemotaxis; positive regulation of cytosolic calcium ion concentration; positive regulation of neutrophil chemotaxis; regulation of cell proliferation; response to lipopolysaccharide; response to molecule of bacterial origin Go Component extracellular region; extracellular space; extracellular space Gene Isoforms NM_009140. Blast Isoform Hits NM_009140 Amplicon Length 65 Exon 3-4 CDS Partial



Entrez Gene ID

Assay ID 330122





Dcip1; Gm1960 CXCR chemokine receptor binding; chemokine activity; chemokine activity; cytokine activity; protein binding G-protein coupled receptor signaling pathway; chemokine-mediated signaling pathway; chemotaxis; defense response; immune response; inflammatory response; inflammatory response; neutrophil chemotaxis; neutrophil chemotaxis; positive regulation of cytosolic calcium ion concentration; positive regulation of neutrophil chemotaxis; regulation of cell proliferation; response to lipopolysaccharide Go Component extracellular region; extracellular space; extracellular space Gene Isoforms NM_203320. Blast Isoform Hits NM_203320 Amplicon Length 95 Exon 2-3 CDS Full

7690_DGP_17.T1

19/64



Entrez Gene ID

Assay ID 20311





LIX; Cxcl6; GCP-2; Scyb5; Scyb6; ENA-78; AMCF-II CXCR chemokine receptor binding; chemokine activity; chemokine activity; cytokine activity G-protein coupled receptor signaling pathway; animal organ regeneration; chemokine-mediated signaling pathway; chemotaxis; cytokine production; defense response; immune response; inflammatory response; inflammatory response; leukocyte homeostasis; positive regulation of JAK-STAT cascade; positive regulation of neuron projection development; positive regulation of neutrophil chemotaxis; regulation of cell proliferation; regulation of chemokine production; regulation of neutrophil mediated killing of gram-negative bacterium; response to lipopolysaccharide Go Component extracellular region; extracellular space; extracellular space Gene Isoforms NM_009141.N Blast Isoform Hits NM_009141 Amplicon Length 70 Exon 1-2 CDS Full



Entrez Gene ID

Assay ID 17329





CMK; Mig; MuMIG; Scyb9; crg-10; BB139920 CXCR3 chemokine receptor binding; chemokine activity; cytokine activity G-protein coupled receptor signaling pathway; T cell chemotaxis; chemokine-mediated signaling pathway; chemotaxis; defense response; defense response to virus; immune response; inflammatory response; positive regulation of leukocyte chemotaxis; positive regulation of myoblast differentiation; positive regulation of myoblast fusion; regulation of cell proliferation; response to lipopolysaccharide Go Component external side of plasma membrane; extracellular region; extracellular space Gene Isoforms NM_008599. Blast Isoform Hits NM_008599 Amplicon Length 75 Exon 1-2 CDS Full

7690_DGP_17.T1

20/64


DICER1_80835_i25 Dicer1

Entrez Gene ID

Assay ID 192119


Official Full Name dicer 1, ribonuclease type III Related IDs



D12Ertd7e; mKIAA0928; 1110006F08Rik ATP binding; DNA binding; RNA binding; double-stranded RNA binding; endonuclease activity; endoribonuclease activity; endoribonuclease activity, producing 5'-phosphomonoesters; helicase activity; hydrolase activity; metal ion binding; miRNA binding; nuclease activity; nucleotide binding; pre-miRNA binding; pre-miRNA binding; protein binding; protein domain specific binding; ribonuclease III activity; ribonuclease III activity; ribonuclease III activity; ribonuclease III activity; siRNA binding

Go Process

RNA interference; RNA phosphodiester bond hydrolysis, endonucleolytic; RNA processing; RNA processing; anatomical structure development; angiogenesis; branching morphogenesis of an epithelial tube; cardiac muscle cell development; cardiac neural crest cell development involved in outflow tract morphogenesis; cartilage development; cell proliferation; cerebral cortex development; chromatin silencing at centromere outer repeat region; conversion of ds siRNA to ss siRNA; conversion of ds siRNA to ss siRNA involved in RNA interference; defense response to virus; digestive tract development; embryonic hindlimb morphogenesis; embryonic limb morphogenesis; epidermis morphogenesis; ganglion development; gene silencing by RNA; hair follicle cell proliferation; hair follicle development; hair follicle morphogenesis; inner ear receptor cell development; intestinal epithelial cell development; lung development; mRNA stabilization; meiotic spindle organization; miRNA loading onto RISC involved in gene silencing by miRNA; multicellular organism growth; myoblast differentiation involved in skeletal muscle regeneration; negative regulation of Schwann cell proliferation; negative regulation of glial cell proliferation; negative regulation of transcription from RNA polymerase II promoter; nerve development; neuron projection morphogenesis; olfactory bulb interneuron differentiation; peripheral nervous system myelin formation; positive regulation of Schwann cell differentiation; positive regulation of gene expression; positive regulation of miRNA metabolic process; positive regulation of myelination; positive regulation of transcription from RNA polymerase II promoter; post-embryonic development; pre-miRNA processing; pre-miRNA processing; pre-miRNA processing; production of miRNAs involved in gene silencing by miRNA; production of miRNAs involved in gene silencing by miRNA; production of siRNA involved in RNA interference; production of siRNA involved in RNA interference; production of siRNA involved in RNA interference; production of siRNA involved in RNA interference; rRNA catabolic process; regulation of Notch signaling pathway; regulation of RNA metabolic process; regulation of cell cycle; regulation of cell differentiation; regulation of enamel mineralization; regulation of gene expression; regulation of inflammatory response; regulation of miRNA metabolic process; regulation of muscle cell apoptotic process; regulation of myelination; regulation of neurogenesis; regulation of neuron differentiation; regulation of odontogenesis of dentin-containing tooth; regulation of oligodendrocyte differentiation; regulation of protein phosphorylation; regulation of regulatory T cell differentiation; regulation of stem cell differentiation; regulation of viral genome replication; reproductive structure development; siRNA loading onto RISC involved in RNA interference; spinal cord motor neuron differentiation; spindle assembly; spleen development; stem cell population maintenance; targeting of mRNA for destruction involved in RNA interference; zygote asymmetric cell division

Go Component

RISC complex; RISC-loading complex; axon; cytoplasm; cytoplasm; dendrite; endoplasmic reticulum-Golgi intermediate compartment; growth cone; micro-ribonucleoprotein complex; nucleus Gene Isoforms NM_148948. Blast Isoform Hits NM_148948 Amplicon Length 82 Exon 26-27 CDS Full

7690_DGP_17.T1

21/64


FKBP1A_80866_i3 Fkbp1a

Entrez Gene ID

Assay ID 14225


Official Full Name FK506 binding protein 1a Related IDs



Fkbp; Fkbp1; FKBP12 FK506 binding; FK506 binding; Hsp70 protein binding; SMAD binding; activin binding; drug binding; enzyme binding; ion channel binding; isomerase activity; peptidyl-prolyl cis-trans isomerase activity; peptidyl-prolyl cistrans isomerase activity; protein binding; protein homodimerization activity; signal transducer activity; transforming growth factor beta receptor binding; type I transforming growth factor beta receptor binding SMAD protein complex assembly; T cell proliferation; amyloid fibril formation; chaperone-mediated protein folding; cytokine-mediated signaling pathway; heart morphogenesis; heart trabecula formation; muscle contraction; negative regulation of phosphoprotein phosphatase activity; negative regulation of protein phosphorylation; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of protein binding; positive regulation of protein ubiquitination; protein peptidyl-prolyl isomerization; regulation of activin receptor signaling pathway; regulation of amyloid precursor protein catabolic process; regulation of immune response; regulation of protein localization; regulation of ryanodine-sensitive calcium-release channel activity; regulation of ryanodinesensitive calcium-release channel activity; release of sequestered calcium ion into cytosol; release of sequestered calcium ion into cytosol; response to caffeine; supramolecular fiber organization; ventricular cardiac muscle tissue morphogenesis

Go Process

Go Component

Z disc; axon terminus; cytoplasm; cytosol; extracellular exosome; intracellular membrane-bounded organelle; membrane; membrane; sarcoplasmic reticulum membrane Gene Isoforms NM_008019.; NM_001302077.; NM_001302080.; NM_001302079.; NM_001302078.; NR_126058. Blast Isoform Hits NM_001302080; NM_001302077; NM_001302079; NM_008019; NM_001302078 Amplicon Length 69 Exon 4-5 CDS Full


ICP0_80789_e0 FLDM-028308

Assay ID Entrez Gene ID


Official Full Name Related IDs Also known as GO Function Go Process Go Component Gene Isoforms Blast Isoform Hits FLDM-023561.1 Amplicon Length 73

7690_DGP_17.T1

Exon

1

CDS

None

22/64


ICP47_80792_e0 FLDM-042040




Exon

1

CDS

None


ICP34.5_80791_e0 FLDM-058211




7690_DGP_17.T1

Exon

1

CDS

None

23/64


ICP27_80793_e0 FLDM-071568




Exon

1

CDS

None


GAPDH_80797_e4 Gapdh

Entrez Gene ID

Assay ID 14433


Official Full Name glyceraldehyde-3-phosphate dehydrogenase Related IDs



Gapd disordered domain specific binding; enzyme binding; glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity; glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity; glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity; identical protein binding; microtubule binding; peptidyl-cysteine S-nitrosylase activity; protein binding apoptotic process; carbohydrate metabolic process; cellular response to interferon-gamma; gluconeogenesis; glycolytic process; microtubule cytoskeleton organization; multicellular organism development; negative regulation of translation; negative regulation of translation; neuron apoptotic process; peptidyl-cysteine S-trans-nitrosylation; protein stabilization; response to ammonium ion GAIT complex; GAIT complex; cytoplasm; cytoplasm; cytosol; cytosol; extracellular exosome; extracellular matrix; intracellular membrane-bounded organelle; intracellular ribonucleoprotein complex; lipid particle; membrane; microtubule cytoskeleton; mitochondrion; myelin sheath; nuclear membrane; nucleus; plasma membrane; vesicle

Go Process

Go Component

Gene Isoforms NM_008084.; NM_001289726. Blast Isoform Hits NR_002890; NM_001289726; NM_008084 Amplicon Length 82 Exon 5

7690_DGP_17.T1

CDS

Full

24/64


HMGB1_80856_e4 Hmgb1

Entrez Gene ID

Assay ID 15289


Official Full Name high mobility group box 1 Related IDs



p30; Hmg1; HMG-1; SBP-1 bent DNA binding; calcium-dependent protein kinase regulator activity; crossed form four-way junction DNA binding; cytokine activity; cytokine activity; double-stranded DNA binding; double-stranded RNA binding; open form four-way junction DNA binding; phosphatidylserine binding; protein binding; protein kinase activator activity; single-stranded RNA binding Go Process DNA geometric change; base-excision repair; chromatin assembly; endothelial cell chemotaxis; endothelial cell proliferation; eye development; induction of positive chemotaxis; inflammatory response; lung development; macrophage activation involved in immune response; myeloid dendritic cell activation; negative regulation of apoptotic cell clearance; plasmacytoid dendritic cell activation; positive regulation of ERK1 and ERK2 cascade; positive regulation of NIK/NF-kappaB signaling; positive regulation of cell migration; positive regulation of glycogen catabolic process; positive regulation of innate immune response; positive regulation of interferon-alpha production; positive regulation of interferon-beta production; positive regulation of interleukin-1 beta secretion; positive regulation of interleukin-6 production; positive regulation of mesenchymal cell proliferation; positive regulation of mitotic cell cycle; positive regulation of myeloid cell differentiation; positive regulation of protein phosphorylation; positive regulation of sprouting angiogenesis; positive regulation of toll-like receptor 2 signaling pathway; positive regulation of toll-like receptor 4 signaling pathway; positive regulation of transcription from RNA polymerase II promoter; positive regulation of tumor necrosis factor production; positive regulation of wound healing; regulation of T cell mediated immune response to tumor cell; regulation of autophagy; regulation of nucleotide-excision repair; regulation of tolerance induction; response to glucocorticoid Go Component cytoplasm; early endosome; extracellular region; extracellular space; neuron projection; nucleus Gene Isoforms NM_001313894.; NM_010439. Blast Isoform Hits NM_001313894; NM_010439 Amplicon Length 91 Exon 5 CDS None

7690_DGP_17.T1

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IDO1_80818_i6 Ido1

Entrez Gene ID

Assay ID 15930


Official Full Name indoleamine 2,3-dioxygenase 1 Related IDs



Ido; Indo amino acid binding; dioxygenase activity; heme binding; indoleamine 2,3-dioxygenase activity; metal ion binding; oxidoreductase activity; oxygen binding; protein binding; tryptophan 2,3-dioxygenase activity; tryptophan 2,3dioxygenase activity

Go Process

cytokine production involved in inflammatory response; defense response; immune system process; inflammatory response; kynurenic acid biosynthetic process; multicellular organismal response to stress; negative regulation of T cell apoptotic process; negative regulation of T cell proliferation; negative regulation of activated T cell proliferation; negative regulation of interleukin-10 production; oxidation-reduction process; positive regulation of T cell apoptotic process; positive regulation of T cell tolerance induction; positive regulation of apoptotic process; positive regulation of chronic inflammatory response; positive regulation of interleukin-12 production; positive regulation of type 2 immune response; response to lipopolysaccharide; swimming behavior; tryptophan catabolic process; tryptophan catabolic process to kynurenine; tryptophan catabolic process to kynurenine


cytoplasm; cytosol; smooth muscle contractile fiber; stereocilium bundle NM_008324.; NM_001293690. NM_008324; NM_001293690 80 Exon 7-8 CDS Full


IFNA1_80821_e0 Ifna1

Entrez Gene ID

Assay ID 15962


Official Full Name interferon alpha 1 Related IDs



Ifa1 cytokine activity; cytokine receptor binding; type I interferon receptor binding B cell differentiation; B cell proliferation; T cell activation involved in immune response; adaptive immune response; cytokine-mediated signaling pathway; defense response; defense response to bacterium; defense response to virus; humoral immune response; innate immune response; natural killer cell activation involved in immune response; positive regulation of peptidyl-serine phosphorylation of STAT protein; regulation of defense response to virus by host; response to exogenous dsRNA; type I interferon signaling pathway


extracellular region; extracellular space; intracellular NM_010502. NM_010502 88 Exon 1 CDS

7690_DGP_17.T1

Full

26/64


IKBKB_80879_i8 Ikbkb

Entrez Gene ID

Assay ID 16150


Official Full Name inhibitor of kappaB kinase beta Related IDs



IKK2; IKK-2; IKK[b]; IKKbeta; AI132552; IKK-beta ATP binding; IkappaB kinase activity; kinase activity; nucleotide binding; protein binding; protein heterodimerization activity; protein homodimerization activity; protein kinase activity; protein kinase activity; protein kinase activity; protein kinase binding; protein serine/threonine kinase activity; scaffold protein binding; signal transducer, downstream of receptor, with serine/threonine kinase activity; transferase activity Go Process B cell homeostasis; I-kappaB kinase/NF-kappaB signaling; I-kappaB phosphorylation; anatomical structure morphogenesis; cellular response to tumor necrosis factor; cortical actin cytoskeleton organization; establishment of protein localization to plasma membrane; inflammatory response; innate immune response; interleukin-1mediated signaling pathway; negative regulation of bicellular tight junction assembly; negative regulation of myosin-light-chain-phosphatase activity; neuron projection development; peptidyl-serine phosphorylation; phosphorylation; positive regulation of NF-kappaB transcription factor activity; positive regulation of NF-kappaB transcription factor activity; positive regulation of cation channel activity; positive regulation of cell proliferation; positive regulation of neuron death; positive regulation of neuron projection development; positive regulation of sodium ion transport; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; protein phosphorylation; regulation of establishment of endothelial barrier; regulation of phosphorylation; serine phosphorylation of STAT protein; tumor necrosis factormediated signaling pathway; tumor necrosis factor-mediated signaling pathway Go Component CD40 receptor complex; IkappaB kinase complex; IkappaB kinase complex; cytoplasm; cytoplasmic side of plasma membrane; cytosol; intracellular membrane-bounded organelle; membrane; nucleus Gene Isoforms NM_010546.N; NM_001159774.N Blast Isoform Hits NM_001159774; NM_010546 Amplicon Length 86 Exon 9-10 CDS Full

7690_DGP_17.T1

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IL10_2698_i1 Il10

Entrez Gene ID

Assay ID 16153


Official Full Name interleukin 10 Related IDs



CSIF; Il-10 cytokine activity; cytokine activity; interleukin-10 receptor binding branching involved in labyrinthine layer morphogenesis; cellular response to hepatocyte growth factor stimulus; cellular response to lipopolysaccharide; defense response to bacterium; defense response to protozoan; immune response; inflammatory response; negative regulation of B cell proliferation; negative regulation of apoptotic process; negative regulation of cell proliferation; negative regulation of chronic inflammatory response to antigenic stimulus; negative regulation of cytokine activity; negative regulation of cytokine production; negative regulation of cytokine secretion involved in immune response; negative regulation of endothelial cell apoptotic process; negative regulation of growth of symbiont in host; negative regulation of heterotypic cell-cell adhesion; negative regulation of inflammatory response; negative regulation of inflammatory response; negative regulation of interferon-gamma production; negative regulation of interleukin-12 production; negative regulation of interleukin6 production; negative regulation of membrane protein ectodomain proteolysis; negative regulation of myeloid dendritic cell activation; negative regulation of nitric oxide biosynthetic process; negative regulation of sensory perception of pain; negative regulation of tumor necrosis factor biosynthetic process; negative regulation of tumor necrosis factor production; negative regulation of vascular smooth muscle cell proliferation; positive regulation of B cell apoptotic process; positive regulation of MHC class II biosynthetic process; positive regulation of cell cycle; positive regulation of cytokine secretion; positive regulation of endothelial cell proliferation; positive regulation of macrophage activation; positive regulation of sequence-specific DNA binding transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-templated; receptor biosynthetic process; regulation of gene expression; regulation of response to wounding; regulation of sensory perception of pain; regulation of synapse organization; response to glucocorticoid; response to molecule of bacterial origin Go Component extracellular region; extracellular space; extracellular space Gene Isoforms NM_010548. Blast Isoform Hits NM_010548 Amplicon Length 79 Exon 2-3 CDS Full

7690_DGP_17.T1

28/64


IL12A_80838_i2 Il12a

Entrez Gene ID

Assay ID 16159


Official Full Name interleukin 12a Related IDs



p35; Ll12a; Il-12a; IL-12p35 cytokine activity; cytokine activity; growth factor activity; interleukin-12 beta subunit binding; interleukin-12 beta subunit binding; interleukin-12 receptor binding; interleukin-27 binding; protein heterodimerization activity cell cycle arrest; cell migration; cellular response to lipopolysaccharide; cellular response to virus; defense response to protozoan; defense response to protozoan; extrinsic apoptotic signaling pathway; immune response; negative regulation of interleukin-17 production; negative regulation of smooth muscle cell proliferation; positive regulation of NK T cell activation; positive regulation of T cell differentiation; positive regulation of T cell mediated cytotoxicity; positive regulation of T cell proliferation; positive regulation of cell adhesion; positive regulation of dendritic cell chemotaxis; positive regulation of interferon-gamma production; positive regulation of interferongamma production; positive regulation of interferon-gamma production; positive regulation of lymphocyte proliferation; positive regulation of mononuclear cell proliferation; positive regulation of natural killer cell activation; positive regulation of natural killer cell mediated cytotoxicity; positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; positive regulation of smooth muscle cell apoptotic process; response to UV-B; response to lipopolysaccharide

Go Process

Go Component

cytoplasm; extracellular region; extracellular space; extracellular space; interleukin-12 complex; interleukin-12 complex; interleukin-12 complex Gene Isoforms NM_008351.; NM_001159424. Blast Isoform Hits NM_001159424; NM_008351 Amplicon Length 80 Exon 3-4 CDS Full

7690_DGP_17.T1

29/64


IL12B_80837_i1 Il12b

Entrez Gene ID

Assay ID 16160


Official Full Name interleukin 12b Related IDs



p40; Il-12b; Il12p40; Il-12p40 cytokine activity; cytokine activity; cytokine receptor activity; cytokine receptor binding; growth factor activity; identical protein binding; interleukin-12 alpha subunit binding; interleukin-12 alpha subunit binding; interleukin-23 receptor binding; protein binding; protein heterodimerization activity; protein homodimerization activity

Go Process

T-helper cell differentiation; cell cycle arrest; cell migration; cell surface receptor signaling pathway; cellular response to interferon-gamma; cellular response to lipopolysaccharide; defense response to Gram-negative bacterium; defense response to protozoan; defense response to protozoan; defense response to protozoan; defense response to virus; natural killer cell activation; natural killer cell activation involved in immune response; negative regulation of growth of symbiont in host; negative regulation of inflammatory response to antigenic stimulus; negative regulation of interleukin-10 production; negative regulation of interleukin-17 production; negative regulation of smooth muscle cell proliferation; positive regulation of NK T cell activation; positive regulation of NK T cell proliferation; positive regulation of T cell mediated cytotoxicity; positive regulation of T cell proliferation; positive regulation of T cell proliferation; positive regulation of T-helper 1 type immune response; positive regulation of T-helper 1 type immune response; positive regulation of activated T cell proliferation; positive regulation of cell adhesion; positive regulation of defense response to virus by host; positive regulation of defense response to virus by host; positive regulation of granulocyte macrophage colony-stimulating factor production; positive regulation of interferon-gamma production; positive regulation of interferon-gamma production; positive regulation of interferon-gamma production; positive regulation of interferon-gamma production; positive regulation of interleukin-10 production; positive regulation of interleukin-12 production; positive regulation of interleukin-17 production; positive regulation of lymphocyte proliferation; positive regulation of mononuclear cell proliferation; positive regulation of natural killer cell activation; positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; positive regulation of natural killer cell proliferation; positive regulation of osteoclast differentiation; positive regulation of smooth muscle cell apoptotic process; positive regulation of tumor necrosis factor production; response to UV-B; response to organic substance; sensory perception of pain

Go Component

cytoplasm; extracellular region; extracellular space; extracellular space; interleukin-12 complex; interleukin-12 complex; interleukin-12 complex; interleukin-23 complex; interleukin-23 complex; membrane Gene Isoforms NM_001303244.N Blast Isoform Hits NM_001303244 Amplicon Length 80 Exon 2-3 CDS Full

7690_DGP_17.T1

30/64


IL15_80842_i6 Il15

Entrez Gene ID

Assay ID 16168





IL-15; AI503618 cytokine activity; cytokine activity; cytokine receptor binding NK T cell proliferation; cell maturation; extrathymic T cell selection; hyaluronan metabolic process; immune response; interleukin-15-mediated signaling pathway; lymph node development; natural killer cell differentiation; negative regulation of smooth muscle cell proliferation; positive regulation of T cell proliferation; positive regulation of cell proliferation; positive regulation of immune response; positive regulation of interleukin-17 production; positive regulation of natural killer cell differentiation; positive regulation of natural killer cell differentiation; positive regulation of natural killer cell proliferation; positive regulation of protein O-linked glycosylation; regulation of T cell differentiation; regulation of defense response to virus by host Go Component cell surface; cytoplasm; cytosol; extracellular region; extracellular space; nuclear speck; nucleoplasm Gene Isoforms NM_001254747.; NM_008357. Blast Isoform Hits NM_001254747; NM_008357 Amplicon Length 88 Exon 7-8 CDS Full

7690_DGP_17.T1

31/64


IL1B_2825_i1 Il1b

Entrez Gene ID

Assay ID 16176


Official Full Name interleukin 1 beta Related IDs



Il-1b; IL-1beta cytokine activity; cytokine activity; interleukin-1 receptor binding; protein domain specific binding MAPK cascade; activation of MAPK activity; cellular response to drug; cellular response to organic cyclic compound; cellular response to organic substance; cytokine-mediated signaling pathway; cytokine-mediated signaling pathway; ectopic germ cell programmed cell death; extrinsic apoptotic signaling pathway in absence of ligand; fever generation; hyaluronan biosynthetic process; immune response; inflammatory response; interleukin1 beta production; leukocyte migration; lipopolysaccharide-mediated signaling pathway; memory; monocyte aggregation; negative regulation of MAP kinase activity; negative regulation of adiponectin secretion; negative regulation of branching morphogenesis of a nerve; negative regulation of cell proliferation; negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; negative regulation of gene expression; negative regulation of glucose transport; negative regulation of glutamate secretion; negative regulation of insulin receptor signaling pathway; negative regulation of lipid catabolic process; negative regulation of lipid metabolic process; negative regulation of neural precursor cell proliferation; negative regulation of neurogenesis; negative regulation of neuron differentiation; negative regulation of transcription from RNA polymerase II promoter; neutrophil chemotaxis; positive regulation of ERK1 and ERK2 cascade; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of I-kappaB kinase/NFkappaB signaling; positive regulation of JNK cascade; positive regulation of JNK cascade; positive regulation of JNK cascade; positive regulation of JUN kinase activity; positive regulation of NF-kappaB import into nucleus; positive regulation of NF-kappaB transcription factor activity; positive regulation of T cell proliferation; positive regulation of angiogenesis; positive regulation of apoptotic process; positive regulation of astrocyte differentiation; positive regulation of calcidiol 1-monooxygenase activity; positive regulation of cell death; positive regulation of cell division; positive regulation of chemokine biosynthetic process; positive regulation of cytosolic calcium ion concentration; positive regulation of fever generation; positive regulation of gene expression; positive regulation of gene expression; positive regulation of glial cell differentiation; positive regulation of granulocyte macrophage colony-stimulating factor production; positive regulation of heterotypic cell-cell adhesion; positive regulation of immature T cell proliferation in thymus; positive regulation of interferon-gamma production; positive regulation of interleukin-2 biosynthetic process; positive regulation of interleukin-6 biosynthetic process; positive regulation of interleukin-6 production; positive regulation of interleukin-6 production; positive regulation of interleukin-6 secretion; positive regulation of interleukin-8 production; positive regulation of lipid catabolic process; positive regulation of membrane protein ectodomain proteolysis; positive regulation of mitotic nuclear division; positive regulation of monocyte chemotactic protein-1 production; positive regulation of myosin light chain kinase activity; positive regulation of neuron apoptotic process; positive regulation of neutrophil chemotaxis; positive regulation of nitric oxide biosynthetic process; positive regulation of phagocytosis; positive regulation of prostaglandin secretion; positive regulation of protein phosphorylation; positive regulation of sequence-specific DNA binding transcription factor activity; positive regulation of stress-activated MAPK cascade; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-templated; positive regulation of vascular endothelial growth factor production; positive regulation of vascular endothelial growth factor production; protein kinase B signaling; regulation of I-kappaB kinase/NF-kappaB signaling; regulation of defense response to virus by host; regulation of establishment of endothelial barrier; regulation of insulin secretion; regulation of nitric-oxide synthase activity; regulation of nitricoxide synthase activity; response to ATP; response to ATP; response to carbohydrate; response to lipopolysaccharide; response to lipopolysaccharide; sequestering of triglyceride; social behavior

Go Component

cytoplasm; cytoplasmic vesicle; extracellular region; extracellular space; extracellular space; lysosome; secretory granule; vesicle Gene Isoforms NM_008361. Blast Isoform Hits NM_008361 Amplicon Length 83 Exon 2-3 CDS Full

7690_DGP_17.T1

32/64


IL1RN_80817_i2 Il1rn

Entrez Gene ID

Assay ID 16181


Official Full Name interleukin 1 receptor antagonist Related IDs



IL-1ra; F630041P17Rik cytokine activity; interleukin-1 Type I receptor antagonist activity; interleukin-1 Type II receptor antagonist activity; interleukin-1 receptor antagonist activity; interleukin-1 receptor binding; interleukin-1 receptor binding; interleukin-1, Type I receptor binding; interleukin-1, Type II receptor binding

Go Process

acute-phase response; cytokine-mediated signaling pathway; fever generation; immune response; inflammatory response; insulin secretion; lipid metabolic process; memory; negative regulation of apoptotic process; negative regulation of cell migration; negative regulation of glutamate secretion; negative regulation of heterotypic cell-cell adhesion; negative regulation of interleukin-1-mediated signaling pathway; negative regulation of membrane potential; positive regulation of JUN kinase activity; response to glucocorticoid; sensory perception of pain


cytoplasm; extracellular exosome; extracellular region; extracellular space; extracellular space; vesicle NM_031167.N; NM_001039701.N; NM_001159562.N NM_001159562; NM_031167; NM_001039701 97 Exon 3-4 CDS Full


IL27_80813_i2 Il27

Entrez Gene ID

Assay ID 246779





p28; Il30; IL-27; IL-27p28 cytokine activity; interleukin-27 receptor binding; protein binding; receptor binding immune system process; inflammatory response; innate immune response; positive regulation of defense response to virus by host; positive regulation of defense response to virus by host; positive regulation of interferon -gamma biosynthetic process; positive regulation of interferon-gamma biosynthetic process; regulation of T cell proliferation; regulation of T-helper 1 cell differentiation; regulation of T-helper 1 cell differentiation Go Component extracellular region; extracellular space Gene Isoforms NM_145636. Blast Isoform Hits NM_145636 Amplicon Length 80 Exon 3-4 CDS Full

7690_DGP_17.T1

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IL3_80836_i2 Il3

Entrez Gene ID

Assay ID 16187





BPA; PSF; HCGF; Il-3; MCGF; Csfmu cytokine activity; cytokine activity; growth factor activity; interleukin-1 receptor binding; interleukin-3 receptor binding; interleukin-3 receptor binding Go Process activation of Janus kinase activity; cytokine-mediated signaling pathway; extrinsic apoptotic signaling pathway in absence of ligand; hemopoiesis; immune response; interleukin-3-mediated signaling pathway; monocyte differentiation; myeloid cell apoptotic process; negative regulation of apoptotic process; negative regulation of autophagy; negative regulation of mast cell apoptotic process; positive regulation of JNK cascade; positive regulation of JNK cascade; positive regulation of cell proliferation; positive regulation of cell proliferation; positive regulation of cell proliferation; positive regulation of mast cell proliferation; positive regulation of myeloid leukocyte differentiation; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of protein phosphorylation; regulation of cell growth; regulation of cell growth; regulation of gene expression; regulation of glycolytic process; regulation of protein dephosphorylation; response to hormone; response to hypoxia Go Component extracellular region; extracellular space; extracellular space Gene Isoforms NM_010556.N Blast Isoform Hits NM_010556 Amplicon Length 89 Exon 3-4 CDS Full


IL4RA_80823_i5 Il4ra

Entrez Gene ID

Assay ID 16190


Official Full Name interleukin 4 receptor, alpha Related IDs



Il4r; CD124 cytokine receptor activity; protein binding defense response to protozoan; immune system process; immunoglobulin mediated immune response; negative regulation of T-helper 1 cell differentiation; positive regulation of T-helper 2 cell differentiation; positive regulation of chemokine secretion; positive regulation of immunoglobulin production; positive regulation of macrophage activation; positive regulation of mast cell degranulation; positive regulation of myoblast fusion; production of molecular mediator involved in inflammatory response; regulation of cell proliferation

Go Component

extracellular region; extracellular space; integral component of membrane; membrane; plasma membrane; receptor complex Gene Isoforms NM_001008700. Blast Isoform Hits NM_001008700 Amplicon Length 71 Exon 6-7 CDS Full

7690_DGP_17.T1

34/64


IL6_80801_i3 Il6

Entrez Gene ID

Assay ID 16193





Il-6 cytokine activity; cytokine activity; growth factor activity; interleukin-6 receptor binding; interleukin-6 receptor binding; interleukin-6 receptor binding; protein binding; receptor binding Go Process T cell activation; T-helper 17 cell lineage commitment; acute-phase response; branching involved in salivary gland morphogenesis; branching involved in salivary gland morphogenesis; cell growth; cell redox homeostasis; cellular response to hepatocyte growth factor stimulus; cellular response to hydrogen peroxide; cellular response to interleukin-1; cellular response to lipopolysaccharide; cellular response to lipopolysaccharide; cellular response to tumor necrosis factor; cytokine-mediated signaling pathway; defense response to protozoan; defense response to virus; endocrine pancreas development; epithelial cell proliferation involved in salivary gland morphogenesis; glucagon secretion; glucose homeostasis; hepatic immune response; immune response; inflammatory response; interleukin-6-mediated signaling pathway; interleukin-6-mediated signaling pathway; muscle cell cellular homeostasis; myeloid cell homeostasis; negative regulation of apoptotic process; negative regulation of bone resorption; negative regulation of cell proliferation; negative regulation of chemokine biosynthetic process; negative regulation of chemokine biosynthetic process; negative regulation of collagen biosynthetic process; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of cytokine secretion; negative regulation of gluconeogenesis; negative regulation of hormone secretion; negative regulation of interleukin-1-mediated signaling pathway; negative regulation of membrane potential; negative regulation of muscle organ development; negative regulation of neuron death; negative regulation of protein kinase activity; neuron projection development; neutrophil apoptotic process; neutrophil apoptotic process; neutrophil apoptotic process; positive regulation of B cell activation; positive regulation of DNA replication; positive regulation of ERK1 and ERK2 cascade; positive regulation of JAK-STAT cascade; positive regulation of MAPK cascade; positive regulation of T cell proliferation; positive regulation of T-helper 2 cell cytokine production; positive regulation of T-helper 2 cell differentiation; positive regulation of acute inflammatory response; positive regulation of apoptotic process; positive regulation of cell proliferation; positive regulation of cell proliferation in bone marrow; positive regulation of chemokine production; positive regulation of epithelial cell proliferation; positive regulation of epithelial cell proliferation; positive regulation of gene expression; positive regulation of gene expression; positive regulation of immunoglobulin secretion; positive regulation of interleukin-6 production; positive regulation of neuron differentiation; positive regulation of neuron projection development; positive regulation of nitric oxide biosynthetic process; positive regulation of peptidyl-serine phosphorylation; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of protein import into nucleus, translocation; positive regulation of protein kinase B signaling; positive regulation of sequence-specific DNA binding transcription factor activity; positive regulation of smooth muscle cell proliferation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-templated; positive regulation of transcription, DNA-templated; positive regulation of translation; positive regulation of transmission of nerve impulse; regulation of apoptotic process; regulation of cell proliferation; regulation of cell shape; regulation of circadian sleep/wake cycle, non-REM sleep; regulation of vascular endothelial growth factor production; response to glucocorticoid; response to wounding Go Component cytoplasm; external side of plasma membrane; extracellular region; extracellular space; extracellular space; interleukin-6 receptor complex Gene Isoforms NM_031168.; NM_001314054. Blast Isoform Hits NM_001314054 Amplicon Length 87 Exon 4-5 CDS Full

7690_DGP_17.T1

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IRF5_80814_i7 Irf5

Entrez Gene ID

Assay ID 27056


Official Full Name interferon regulatory factor 5 Related IDs



mirf5; AW491843 DNA binding; protein binding; regulatory region DNA binding; sequence-specific DNA binding; transcription factor activity, sequence-specific DNA binding Go Process cytokine-mediated signaling pathway; defense response to virus; immune system process; innate immune response; positive regulation of apoptotic process; positive regulation of transcription from RNA polymerase II promoter; regulation of transcription from RNA polymerase II promoter; regulation of transcription, DNAtemplated; response to muramyl dipeptide; response to peptidoglycan; transcription, DNA-templated Go Component cytoplasm; nucleus Gene Isoforms NM_001252382.; NM_012057.; NM_001311083. Blast Isoform Hits NM_001311083; NM_001252382; NM_012057 Amplicon Length 79 Exon 8-9 CDS Full


LGALS3_80862_i3 Lgals3

Entrez Gene ID

Assay ID 16854


Official Full Name lectin, galactose binding, soluble 3 Related IDs



GBP; L-34; gal3; Mac-2 Fc-gamma receptor I complex binding; IgE binding; RNA binding; advanced glycation end-product receptor activity; carbohydrate binding; chemoattractant activity; disaccharide binding; laminin binding; monosaccharide binding; protein binding

Go Process

RNA splicing; cell differentiation; eosinophil chemotaxis; extracellular matrix organization; immune system process; innate immune response; mRNA processing; macrophage chemotaxis; maintenance of protein location; monocyte chemotaxis; mononuclear cell migration; negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell; negative regulation of T cell receptor signaling pathway; negative regulation of apoptotic process; negative regulation of cell proliferation in bone marrow; negative regulation of endocytosis; negative regulation of endocytosis; negative regulation of extrinsic apoptotic signaling pathway; negative regulation of immunological synapse formation; neutrophil chemotaxis; positive chemotaxis; positive regulation of angiogenesis; positive regulation of calcium ion import; positive regulation of cell proliferation; positive regulation of mononuclear cell migration; positive regulation of serotonin secretion; regulation of T cell apoptotic process; regulation of T cell proliferation; regulation of extrinsic apoptotic signaling pathway via death domain receptors; skeletal system development

Go Component

cell surface; cell surface; cytoplasm; cytoplasm; external side of plasma membrane; extracellular exosome; extracellular matrix; extracellular region; extracellular space; extracellular space; glial cell projection; immunological synapse; immunological synapse; membrane; mitochondrial inner membrane; nucleus; nucleus; proteinaceous extracellular matrix; spliceosomal complex Gene Isoforms NM_010705.; NM_001145953. Blast Isoform Hits NM_010705; NM_001145953 Amplicon Length 76 Exon 4-5 CDS Full

7690_DGP_17.T1

36/64


MARCO_79834_i15 Marco

Entrez Gene ID

Assay ID 17167


Official Full Name macrophage receptor with collagenous structure Related IDs



Ly112; Scara2; AI323439 scavenger receptor activity apoptotic cell clearance; endocytosis; immune system process; innate immune response collagen trimer; integral component of membrane; membrane NM_010766. NM_010766 80 Exon 16-17 CDS Full


MMP2_80828_i5 Mmp2

Entrez Gene ID

Assay ID 17390


Official Full Name matrix metallopeptidase 2 Related IDs



GelA; Clg4a; MMP-2 fibronectin binding; hydrolase activity; metal ion binding; metalloendopeptidase activity; metallopeptidase activity; peptidase activity; serine-type endopeptidase activity; zinc ion binding Go Process angiogenesis; blood vessel maturation; bone trabecula formation; cell migration; cellular response to amino acid stimulus; cellular response to estradiol stimulus; collagen catabolic process; collagen catabolic process; embryo implantation; face morphogenesis; heart development; intramembranous ossification; negative regulation of cell adhesion; negative regulation of vasoconstriction; ovarian follicle development; peripheral nervous system axon regeneration; positive regulation of apoptotic process; positive regulation of cell migration; positive regulation of innate immune response; positive regulation of vascular smooth muscle cell proliferation; prostate gland epithelium morphogenesis; proteolysis; response to drug; response to estrogen; response to hydrogen peroxide; response to hypoxia; response to hypoxia; response to mechanical stimulus; response to oxidative stress; skeletal system morphogenesis; tissue remodeling Go Component cytoplasm; cytoplasm; extracellular matrix; extracellular region; extracellular space; extracellular space; membrane; mitochondrion; nucleus; plasma membrane; proteinaceous extracellular matrix; sarcomere Gene Isoforms NM_008610.N Blast Isoform Hits NM_008610 Amplicon Length 83 Exon 6-7 CDS Full

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MMP9_12886_i0 Mmp9

Entrez Gene ID

Assay ID 17395


Official Full Name matrix metallopeptidase 9 Related IDs



Clg4b; Gel B; MMP-9; B/MMP9; AW743869; pro-MMP-9 endopeptidase activity; fibronectin binding; hydrolase activity; identical protein binding; metal ion binding; metalloendopeptidase activity; metalloendopeptidase activity; metallopeptidase activity; metallopeptidase activity; peptidase activity; peptidase activity; protein complex binding; serine-type endopeptidase activity; zinc ion binding

Go Process

cellular response to cadmium ion; cellular response to cell-matrix adhesion; cellular response to reactive oxygen species; collagen catabolic process; collagen catabolic process; embryo implantation; extracellular matrix organization; extracellular matrix organization; heart development; leukocyte migration; negative regulation of apoptotic process; negative regulation of cation channel activity; negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; negative regulation of fibroblast proliferation; negative regulation of intrinsic apoptotic signaling pathway; ossification; positive regulation of DNA binding; positive regulation of angiogenesis; positive regulation of apoptotic process; positive regulation of epidermal growth factor receptor signaling pathway; positive regulation of keratinocyte migration; positive regulation of leukocyte migration; positive regulation of protein phosphorylation; positive regulation of receptor binding; positive regulation of release of cytochrome c from mitochondria; positive regulation of synaptic plasticity; positive regulation of vascular smooth muscle cell proliferation; protein oligomerization; proteolysis; response to drug; response to oxidative stress; skeletal system development; skeletal system development; tissue remodeling; transformation of host cell by virus

Go Component

extracellular exosome; extracellular matrix; extracellular region; extracellular space; protein complex; proteinaceous extracellular matrix Gene Isoforms NM_013599. Blast Isoform Hits NM_013599 Amplicon Length 78 Exon 1-2 CDS Full


MRC1_49998_i21 Mrc1

Entrez Gene ID

Assay ID 17533


Official Full Name mannose receptor, C type 1 Related IDs



MR; CD206; AW259686 carbohydrate binding; mannose binding; receptor activity; transmembrane signaling receptor activity cellular response to interferon-gamma; cellular response to interleukin-4; cellular response to lipopolysaccharide; endocytosis; receptor-mediated endocytosis Go Component cell surface; endosome; endosome membrane; integral component of membrane; integral component of plasma membrane; membrane; plasma membrane Gene Isoforms NM_008625. Blast Isoform Hits NM_008625 Amplicon Length 83 Exon 22-23 CDS Full

7690_DGP_17.T1

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MSR1_80800_i5 Msr1

Entrez Gene ID

Assay ID 20288


Official Full Name macrophage scavenger receptor 1 Related IDs



MSR; Scvr; MRS-A; MSR-A; SR-AI; SR-AII; Scara1 low-density lipoprotein particle binding; scavenger receptor activity cholesterol transport; endocytosis; lipoprotein transport; plasma lipoprotein particle clearance; positive regulation of cholesterol storage; positive regulation of macrophage derived foam cell differentiation; receptor-mediated endocytosis

Go Component

collagen trimer; cytoplasmic vesicle; cytosol; integral component of membrane; low-density lipoprotein particle; membrane; plasma membrane Gene Isoforms NM_031195.; NM_001113326. Blast Isoform Hits NM_001113326; NM_031195 Amplicon Length 91 Exon 6-7 CDS Full


MX1_79751_i9 Mx1

Entrez Gene ID

Assay ID 17857


Official Full Name MX dynamin-like GTPase 1 Related IDs



Mx; Mx-1; AI893580 GTP binding; GTPase activity; microtubule binding; nucleotide binding; protein binding defense response to virus; dynamin family protein polymerization involved in mitochondrial fission; immune system process; innate immune response; innate immune response; membrane fusion; mitochondrial fission; response to virus; response to virus


cytoplasm; endoplasmic reticulum; membrane; mitochondrial membrane; nucleus; nucleus NM_010846.; NR_003520. NR_003520; NM_010846 76 Exon 10-11 CDS Full

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NFE2L2_80855_i1 Nfe2l2

Entrez Gene ID

Assay ID 18024


Official Full Name nuclear factor, erythroid derived 2, like 2 Related IDs



Nrf2 DNA binding; DNA binding; RNA polymerase II activating transcription factor binding; RNA polymerase II distal enhancer sequence-specific DNA binding; protein binding; protein domain specific binding; protein heterodimerization activity; sequence-specific DNA binding; transcription cofactor binding; transcription factor activity, sequence-specific DNA binding; transcription factor activity, sequence-specific DNA binding; transcription regulatory region sequence-specific DNA binding; transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding Go Process PERK-mediated unfolded protein response; cell redox homeostasis; cellular response to drug; cellular response to fluid shear stress; cellular response to glucose starvation; cellular response to hydrogen peroxide; cellular response to laminar fluid shear stress; cellular response to oxidative stress; cellular response to oxidative stress; cellular response to tumor necrosis factor; endoplasmic reticulum unfolded protein response; inflammatory response; negative regulation of cardiac muscle cell apoptotic process; negative regulation of cell death; negative regulation of endothelial cell apoptotic process; negative regulation of hematopoietic stem cell differentiation; negative regulation of hydrogen peroxide-induced cell death; negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; negative regulation of vascular associated smooth muscle cell migration; positive regulation of angiogenesis; positive regulation of blood coagulation; positive regulation of blood vessel endothelial cell migration; positive regulation of gene expression; positive regulation of gene expression; positive regulation of glucose import; positive regulation of glutathione biosynthetic process; positive regulation of neuron projection development; positive regulation of reactive oxygen species metabolic process; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress; positive regulation of transcription from RNA polymerase II promoter in response to stress; positive regulation of transcription, DNA-templated; positive regulation of transcription, DNA-templated; proteasomal ubiquitin-independent protein catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; protein ubiquitination; regulation of embryonic development; regulation of removal of superoxide radicals; regulation of transcription, DNA-templated; response to endoplasmic reticulum stress; transcription, DNA-templated Go Component Golgi apparatus; centrosome; chromatin; cytoplasm; cytoplasm; cytoplasm; cytosol; cytosol; nucleoplasm; nucleus; nucleus; plasma membrane; protein-DNA complex Gene Isoforms NM_010902.N; NR_132727.N Blast Isoform Hits NM_010902 Amplicon Length 87 Exon 2-3 CDS Full

7690_DGP_17.T1

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NFIL3_80816_i0 Nfil3

Entrez Gene ID

Assay ID 18030


Official Full Name nuclear factor, interleukin 3, regulated Related IDs



E4BP4; AV225605 DNA binding; RNA polymerase II core promoter sequence-specific DNA binding; RNA polymerase II regulatory region sequence-specific DNA binding; protein binding; sequence-specific DNA binding; transcription factor activity, sequence-specific DNA binding; transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding

Go Process

cellular response to interleukin-4; circadian rhythm; immune response; negative regulation of transcription from RNA polymerase II promoter; positive regulation of gene expression; positive regulation of gene expression; regulation of transcription, DNA-templated; rhythmic process; transcription from RNA polymerase II promoter; transcription, DNA-templated Go Component nucleus Gene Isoforms NM_017373.N Blast Isoform Hits NM_017373 Amplicon Length 95 Exon 1-2 CDS None

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NFKB1_13174_i21 Nfkb1

Entrez Gene ID

Assay ID 18033


Official Full Name nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 Related IDs



p50; p105; NF-KB1; p50/p105; NF-kappaB; NF-kappaB1 DNA binding; DNA binding; RNA polymerase II distal enhancer sequence-specific DNA binding; RNA polymerase II regulatory region sequence-specific DNA binding; RNA polymerase II regulatory region sequence-specific DNA binding; RNA polymerase II transcription factor activity, sequence-specific DNA binding; actinin binding; chromatin binding; double-stranded DNA binding; heat shock protein binding; identical protein binding; protein binding; protein heterodimerization activity; protein homodimerization activity; protein homodimerization activity; regulatory region DNA binding; sequence-specific DNA binding; sequence-specific DNA binding; transcription factor activity, sequence-specific DNA binding; transcription regulatory region DNA binding; transcription regulatory region sequence-specific DNA binding; transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding; transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding

Go Process

I-kappaB kinase/NF-kappaB signaling; NIK/NF-kappaB signaling; apoptotic process; cellular response to brainderived neurotrophic factor stimulus; cellular response to carbohydrate stimulus; cellular response to cytokine stimulus; cellular response to diterpene; cellular response to dsRNA; cellular response to glucoside; cellular response to interleukin-1; cellular response to interleukin-6; cellular response to lipopolysaccharide; cellular response to nicotine; cellular response to organic cyclic compound; cellular response to peptide; cellular response to peptide hormone stimulus; cellular response to tumor necrosis factor; innate immune response; lymph node development; negative regulation of apoptotic process; negative regulation of calcidiol 1-monooxygenase activity; negative regulation of cytokine production; negative regulation of gene expression; negative regulation of inflammatory response; negative regulation of interleukin-12 biosynthetic process; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-templated; positive regulation of canonical Wnt signaling pathway; positive regulation of gene expression; positive regulation of gene silencing by miRNA; positive regulation of hyaluronan biosynthetic process; positive regulation of miRNA metabolic process; positive regulation of pri-miRNA transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-templated; regulation of transcription from RNA polymerase II promoter; regulation of transcription, DNA-templated; response to cytokine; response to muscle stretch; response to organic cyclic compound; response to oxidative stress; signal transduction; transcription, DNA-templated Go Component I-kappaB/NF-kappaB complex; cytoplasm; cytoplasm; cytosol; cytosol; mitochondrion; neuron projection; nucleoplasm; nucleus; nucleus; protein complex Gene Isoforms NM_008689. Blast Isoform Hits NM_008689 Amplicon Length 80 Exon 22-23 CDS Full

7690_DGP_17.T1

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NFKBIZ_80016_i3 Nfkbiz

Entrez Gene ID

Assay ID 80859


Official Full Name nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, zeta Related IDs



INAP; Mail; AA408868 protein binding; transcription cofactor activity inflammatory response; regulation of transcription from RNA polymerase II promoter; regulation of transcription, DNA-templated; transcription, DNA-templated Go Component P-body; nuclear speck; nucleus Gene Isoforms NM_030612.; NM_001159394.; NM_001159395. Blast Isoform Hits NM_030612; NM_001159394; NM_001159395 Amplicon Length 82 Exon 4-5 CDS Full


NOS2_80802_i3 Nos2

Entrez Gene ID

Assay ID 18126


Official Full Name nitric oxide synthase 2, inducible Related IDs



iNOS; Nos-2; Nos2a; i-NOS; NOS-II; MAC-NOS FMN binding; Hsp90 protein binding; NADPH-hemoprotein reductase activity; actin binding; arginine binding; betacatenin binding; cAMP-dependent protein kinase regulator activity; cadherin binding; calmodulin binding; flavin adenine dinucleotide binding; heme binding; metal ion binding; nitric-oxide synthase activity; nitric-oxide synthase activity; nitric-oxide synthase binding; oxidoreductase activity; protein binding; protein homodimerization activity; protein homodimerization activity; protein kinase binding; receptor binding; tetrahydrobiopterin binding

Go Process

arginine catabolic process; arginine catabolic process; cellular response to cytokine stimulus; cellular response to drug; cellular response to interferon-gamma; cellular response to lipopolysaccharide; cellular response to organic cyclic compound; circadian rhythm; defense response to bacterium; defense response to bacterium; inflammatory response; interleukin-6 secretion; interleukin-8 secretion; negative regulation of blood pressure; negative regulation of gene expression; negative regulation of gene expression; negative regulation of protein catabolic process; nitric oxide biosynthetic process; nitric oxide biosynthetic process; nitric oxide mediated signal transduction; ovulation from ovarian follicle; oxidation-reduction process; peptidyl-cysteine S-nitrosylation; positive regulation of blood vessel diameter; positive regulation of guanylate cyclase activity; positive regulation of killing of cells of other organism; prostaglandin secretion; regulation of cell proliferation; regulation of cytokine production involved in inflammatory response; regulation of insulin secretion; response to hypoxia; response to lipopolysaccharide; superoxide metabolic process

Go Component

cortical cytoskeleton; cytoplasm; cytoplasm; cytosol; cytosol; extracellular space; intracellular; nucleus; perinuclear region of cytoplasm; perinuclear region of cytoplasm; peroxisome; vesicle membrane Gene Isoforms NM_010927.; NM_001313922.; NM_001313921. Blast Isoform Hits NM_010927; NM_001313922; NM_001313921 Amplicon Length 76 Exon 4-5 CDS Full

7690_DGP_17.T1

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PARP14_80831_i5 Parp14

Entrez Gene ID

Assay ID 547253


Official Full Name poly (ADP-ribose) polymerase family, member 14 Related IDs



ARTD8; CoaSt6; BC021340; mKIAA1268; 1600029O10Rik NAD+ ADP-ribosyltransferase activity; protein binding; transferase activity; transferase activity, transferring glycosyl groups Go Process regulation of transcription, DNA-templated; transcription, DNA-templated Go Component cytoplasm; cytosol; membrane; nucleus Gene Isoforms NM_001039530. Blast Isoform Hits NM_001039530 Amplicon Length 84 Exon 6-7 CDS Full


PARP9_80824_i3 Parp9

Entrez Gene ID

Assay ID 80285


Official Full Name poly (ADP-ribose) polymerase family, member 9 Related IDs



Bal; Bagl; ARTD9; PARP-9; AW214463; BC003281 NAD+ ADP-ribosyltransferase activity; transferase activity DNA repair; cellular response to DNA damage stimulus; double-strand break repair; regulation of response to interferon-gamma Go Component cytoplasm; cytosol; membrane; mitochondrion; nucleoplasm; nucleus Gene Isoforms NM_030253.N Blast Isoform Hits NM_030253 Amplicon Length 95 Exon 4-5 CDS Full

7690_DGP_17.T1

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PDCD1LG2_80861_i3 Pdcd1lg2

Entrez Gene ID

Assay ID 58205


Official Full Name programmed cell death 1 ligand 2 Related IDs



Btdc; B7-DC; PD-L2; F730015O22Rik protein binding negative regulation of T cell proliferation; negative regulation of activated T cell proliferation; negative regulation of interferon-gamma production; negative regulation of interleukin-10 production; positive regulation of T cell proliferation


extracellular exosome; integral component of membrane; membrane; plasma membrane NM_021396.N NM_021396 84 Exon 4-5 CDS Full


PDGFA_80826_i3 Pdgfa

Entrez Gene ID

Assay ID 18590


Official Full Name platelet derived growth factor, alpha Related IDs Also known as GO Function

MGI:MGI:97527; Ensembl:ENSMUSG00000025856; Vega:OTTMUSG00000025151 collagen binding; growth factor activity; platelet-derived growth factor binding; platelet-derived growth factor receptor binding; platelet-derived growth factor receptor binding; protein heterodimerization activity; protein homodimerization activity

Go Process

actin cytoskeleton organization; angiogenesis; animal organ morphogenesis; animal organ morphogenesis; blood coagulation; bone development; cell projection assembly; digestive tract development; digestive tract development; embryonic lung development; hair follicle development; lung alveolus development; multicellular organism development; negative chemotaxis; negative regulation of phosphatidylinositol biosynthetic process; negative regulation of platelet activation; platelet-derived growth factor receptor signaling pathway; plateletderived growth factor receptor signaling pathway; positive regulation of DNA replication; positive regulation of ERK1 and ERK2 cascade; positive regulation of ERK1 and ERK2 cascade; positive regulation of MAP kinase activity; positive regulation of MAP kinase activity; positive regulation of MAPK cascade; positive regulation of cell division; positive regulation of cell migration; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of cell proliferation; positive regulation of fibroblast proliferation; positive regulation of mesenchymal cell proliferation; positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of protein autophosphorylation; positive regulation of protein autophosphorylation; positive regulation of protein kinase B signaling; regulation of branching involved in salivary gland morphogenesis by epithelial-mesenchymal signaling; regulation of peptidyltyrosine phosphorylation; regulation of smooth muscle cell migration; response to wounding; skin development


cell surface; extracellular region; extracellular space; extracellular space; membrane; microvillus NM_008808. NM_008808 89 Exon 4-5 CDS Full

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PDGFC_80829_i1 Pdgfc

Entrez Gene ID

Assay ID 54635


Official Full Name platelet-derived growth factor, C polypeptide Related IDs



PDGF-C; AI647969; 1110064L01Rik growth factor activity; platelet-derived growth factor receptor binding; platelet-derived growth factor receptor binding; protein homodimerization activity activation of transmembrane receptor protein tyrosine kinase activity; animal organ morphogenesis; animal organ morphogenesis; blood coagulation; bone development; cellular response to amino acid stimulus; digestive tract development; embryo development; multicellular organism development; platelet-derived growth factor receptor signaling pathway; platelet-derived growth factor receptor signaling pathway; positive regulation of DNA replication; positive regulation of ERK1 and ERK2 cascade; positive regulation of MAP kinase activity; positive regulation of cell division; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of fibroblast proliferation; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of protein autophosphorylation; regulation of peptidyl-tyrosine phosphorylation

Go Process

Go Component

cell surface; cytoplasm; cytosol; extracellular exosome; extracellular region; extracellular space; extracellular space; membrane; nucleus; plasma membrane Gene Isoforms NM_019971. Blast Isoform Hits NM_019971 Amplicon Length 101 Exon 2-3 CDS Full


PIGF_80833_i4 Pigf

Entrez Gene ID

Assay ID 18701


Official Full Name phosphatidylinositol glycan anchor biosynthesis, class F Related IDs



phosphotransferase activity, for other substituted phosphate groups GPI anchor biosynthetic process endoplasmic reticulum; endoplasmic reticulum membrane; integral component of membrane; membrane NM_008838. NM_008838 84 Exon 5-6 CDS Full

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PRKCB_80878_i4 Prkcb

Entrez Gene ID

Assay ID 18751


Official Full Name protein kinase C, beta Related IDs



Pkcb; PKC-B; Prkcb1; Prkcb2; PKC-Beta ATP binding; androgen receptor binding; calcium channel regulator activity; chromatin binding; histone binding; histone kinase activity (H3-T6 specific); kinase activity; ligand-dependent nuclear receptor transcription coactivator activity; metal ion binding; nucleotide binding; protein binding; protein kinase C activity; protein kinase C activity; protein kinase C binding; protein kinase activity; protein serine/threonine kinase activity; protein serine/threonine kinase activity; transferase activity; zinc ion binding

Go Process

B cell activation; B cell receptor signaling pathway; adaptive immune response; apoptotic process; calcium ion transport; cellular calcium ion homeostasis; cellular response to carbohydrate stimulus; covalent chromatin modification; histone H3-T6 phosphorylation; immune system process; intracellular signal transduction; negative regulation of glucose transport; negative regulation of insulin receptor signaling pathway; peptidyl-serine phosphorylation; phosphorylation; positive regulation of B cell receptor signaling pathway; positive regulation of IkappaB kinase/NF-kappaB signaling; positive regulation of NF-kappaB transcription factor activity; positive regulation of angiogenesis; positive regulation of vascular endothelial growth factor receptor signaling pathway; protein phosphorylation; regulation of dopamine secretion; regulation of growth; regulation of transcription from RNA polymerase II promoter; regulation of transcription, DNA-templated; response to drug; response to hypoxia; response to hypoxia; transcription, DNA-templated

Go Component

brush border membrane; centrosome; cytoplasm; cytoplasm; cytosol; extracellular exosome; membrane; nucleoplasm; nucleus; nucleus; plasma membrane Gene Isoforms NM_008855.; NM_001316672. Blast Isoform Hits NM_001316672; NM_008855 Amplicon Length 76 Exon 5-6 CDS Full


PTMA_80876_i3 Ptma

Entrez Gene ID

Assay ID 19231


Official Full Name prothymosin alpha Related IDs



Thym histone binding histone exchange; histone exchange nucleus NM_008972. NM_008972 116 Exon 4-5

7690_DGP_17.T1

CDS

Partial

47/64


PTPRC_80860_i13 Ptprc

Entrez Gene ID

Assay ID 19264


Official Full Name protein tyrosine phosphatase, receptor type, C Related IDs



loc; B220; Cd45; L-CA; Ly-5; T200; CD45R; Lyt-4 heparan sulfate proteoglycan binding; heparin binding; hydrolase activity; phosphatase activity; phosphoprotein phosphatase activity; protein binding; protein kinase binding; protein kinase binding; protein tyrosine phosphatase activity; protein tyrosine phosphatase activity

Go Process

B cell differentiation; B cell proliferation; B cell receptor signaling pathway; T cell differentiation; T cell proliferation; T cell receptor signaling pathway; activation of MAPK activity; bone marrow development; cell cycle phase transition; defense response to virus; defense response to virus; dephosphorylation; hematopoietic progenitor cell differentiation; heterotypic cell-cell adhesion; immunoglobulin biosynthetic process; leukocyte cellcell adhesion; negative regulation of T cell mediated cytotoxicity; negative regulation of cell adhesion involved in substrate-bound cell migration; negative regulation of cytokine-mediated signaling pathway; negative regulation of peptidyl-tyrosine phosphorylation; negative regulation of protein autophosphorylation; negative regulation of protein kinase activity; negative regulation of protein kinase activity; negative thymic T cell selection; positive regulation of B cell proliferation; positive regulation of B cell proliferation; positive regulation of MAPK cascade; positive regulation of T cell differentiation; positive regulation of T cell mediated cytotoxicity; positive regulation of T cell mediated immunity; positive regulation of T cell proliferation; positive regulation of alpha-beta T cell proliferation; positive regulation of antigen receptor-mediated signaling pathway; positive regulation of extrinsic apoptotic signaling pathway; positive regulation of gamma-delta T cell differentiation; positive regulation of hematopoietic stem cell migration; positive regulation of humoral immune response mediated by circulating immunoglobulin; positive regulation of isotype switching to IgG isotypes; positive regulation of stem cell proliferation; positive thymic T cell selection; protein dephosphorylation; regulation of B cell differentiation; regulation of B cell receptor signaling pathway; regulation of cell cycle; regulation of extrinsic apoptotic signaling pathway; regulation of humoral immune response mediated by circulating immunoglobulin; release of sequestered calcium ion into cytosol; response to gamma radiation; stem cell development cell periphery; cell surface; cell surface; external side of plasma membrane; external side of plasma membrane; extracellular exosome; focal adhesion; integral component of membrane; integral component of plasma membrane; membrane; plasma membrane

Go Component

Gene Isoforms NM_001268286.; NM_011210.; NM_001111316. Blast Isoform Hits NM_001268286; NM_011210; NM_001111316 Amplicon Length 79 Exon 14-15

7690_DGP_17.T1

CDS

Full

48/64


PYCARD_80887_i0 Pycard

Entrez Gene ID

Assay ID 66824


Official Full Name PYD and CARD domain containing Related IDs



Asc; TNS1; masc; CARD5; TMS-1; 9130417A21Rik BMP receptor binding; Pyrin domain binding; cysteine-type endopeptidase activity involved in apoptotic process; enzyme binding; identical protein binding; interleukin-6 receptor binding; ion channel binding; myosin I binding; peptidase activator activity involved in apoptotic process; protease binding; protein binding; protein dimerization activity; protein homodimerization activity; tropomyosin binding activation of cysteine-type endopeptidase activity; activation of cysteine-type endopeptidase activity involved in apoptotic process; activation of innate immune response; activation of innate immune response; apoptotic process; cellular response to interleukin-1; cellular response to lipopolysaccharide; cellular response to tumor necrosis factor; defense response to Gram-negative bacterium; defense response to virus; immune system process; inflammatory response; innate immune response; interleukin-1 beta production; intrinsic apoptotic signaling pathway by p53 class mediator; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; macropinocytosis; myeloid dendritic cell activation; myeloid dendritic cell activation involved in immune response; negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of NF-kappaB transcription factor activity; negative regulation of interferon-beta production; negative regulation of protein serine/threonine kinase activity; positive regulation of ERK1 and ERK2 cascade; positive regulation of ERK1 and ERK2 cascade; positive regulation of JNK cascade; positive regulation of NF-kappaB transcription factor activity; positive regulation of T cell activation; positive regulation of T cell migration; positive regulation of actin filament polymerization; positive regulation of activated T cell proliferation; positive regulation of adaptive immune response; positive regulation of antigen processing and presentation of peptide antigen via MHC class II; positive regulation of apoptotic process; positive regulation of chemokine secretion; positive regulation of chemokine secretion; positive regulation of cysteine-type endopeptidase activity; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; positive regulation of defense response to virus by host; positive regulation of extrinsic apoptotic signaling pathway; positive regulation of interferon-gamma production; positive regulation of interleukin-1 beta secretion; positive regulation of interleukin-1 beta secretion; positive regulation of interleukin-1 beta secretion; positive regulation of interleukin-10 secretion; positive regulation of interleukin-6 production; positive regulation of interleukin-6 secretion; positive regulation of interleukin-8 secretion; positive regulation of phagocytosis; positive regulation of release of cytochrome c from mitochondria; positive regulation of sequence-specific DNA binding transcription factor activity; positive regulation of tumor necrosis factor production; regulation of GTPase activity; regulation of apoptotic process; regulation of autophagy; regulation of cysteine-type endopeptidase activity involved in apoptotic process; regulation of inflammatory response; regulation of intrinsic apoptotic signaling pathway; regulation of protein stability; regulation of tumor necrosis factor-mediated signaling pathway; response to bacterium; tumor necrosis factor-mediated signaling pathway

Go Process

Go Component

AIM2 inflammasome complex; IkappaB kinase complex; NLRP1 inflammasome complex; NLRP3 inflammasome complex; cytoplasm; cytosol; cytosol; endoplasmic reticulum; extracellular region; mitochondrion; neuronal cell body; nucleolus; nucleus; nucleus; protein complex

Gene Isoforms NM_023258.N Blast Isoform Hits NM_023258 Amplicon Length 72

7690_DGP_17.T1

Exon

1-2

CDS

Full

49/64


SBNO2_80820_i19 Sbno2

Entrez Gene ID

Assay ID 216161


Official Full Name strawberry notch homolog 2 (Drosophila) Related IDs



Sno; Stno; BC019206; F730040C21 protein binding bone mineralization; bone trabecula morphogenesis; cell differentiation; cellular response to interleukin-11; cellular response to interleukin-6; cellular response to interleukin-6; cellular response to leukemia inhibitory factor; cellular response to lipopolysaccharide; macrophage activation involved in immune response; macrophage activation involved in immune response; multinuclear osteoclast differentiation; negative regulation of transcription, DNA-templated; negative regulation of transcription, DNA-templated; ossification; osteoclast differentiation; osteoclast fusion; positive regulation of transcription from RNA polymerase II promoter; regulation of inflammatory response; regulation of inflammatory response; regulation of transcription, DNA-templated; transcription, DNA-templated


cellular_component NM_183426.N NM_183426 77 Exon

20-21

CDS

Full


SIRPA_80859_i4 Sirpa

Entrez Gene ID

Assay ID 19261


Official Full Name signal-regulatory protein alpha Related IDs



Bit; P84; SIRP; SHP-1; CD172a; Ptpns1; SHPS-1; AI835480 SH3 domain binding; protein binding; protein phosphorylated amino acid binding actin filament organization; cell migration; cell-matrix adhesion; cytoskeleton organization; hematopoietic progenitor cell differentiation; movement of cell or subcellular component; phagocytosis, engulfment; phagocytosis, recognition; positive regulation of phagocytosis


extracellular exosome; integral component of membrane; integral component of plasma membrane; membrane NM_001291022.; NM_001177647.; NM_007547.; NM_001291021.; NM_001291020.; NM_001291019. NM_001291022; NM_001177647; NM_007547 65 Exon 5-6 CDS Full

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SOCS2_80815_e2 Socs2

Entrez Gene ID

Assay ID 216233


Official Full Name suppressor of cytokine signaling 2 Related IDs



hg; JAB; CIS2; Cish2; SSI-2; SOCS-2; AI527257; AW108012; 8030460M17; D130043N08Rik JAK pathway signal transduction adaptor activity; growth hormone receptor binding; insulin-like growth factor receptor binding; protein kinase inhibitor activity Go Process cellular response to hormone stimulus; cytokine-mediated signaling pathway; growth hormone receptor signaling pathway; intracellular signal transduction; lactation; lactation; mammary gland alveolus development; mammary gland alveolus development; negative regulation of JAK-STAT cascade; negative regulation of insulin receptor signaling pathway; negative regulation of multicellular organism growth; negative regulation of multicellular organism growth; negative regulation of protein kinase activity; negative regulation of signal transduction; positive regulation of neuron differentiation; regulation of cell growth; regulation of growth; regulation of multicellular organism growth; response to estradiol Go Component cytoplasm Gene Isoforms NM_007706.N; NM_001168657.N; NM_001168656.N; NM_001168655.N Blast Isoform Hits NM_001168655; NM_007706; NM_001168656; NM_001168657 Amplicon Length 81 Exon 3 CDS None


SOCS3_56895_i0 Socs3

Entrez Gene ID

Assay ID 12702


Official Full Name suppressor of cytokine signaling 3 Related IDs



Cis3; Ef10; Ssi3; Cish3; EF-10; SSI-3 phosphotyrosine binding; protein binding; protein kinase inhibitor activity JAK-STAT cascade; branching involved in labyrinthine layer morphogenesis; cytokine-mediated signaling pathway; intracellular signal transduction; negative regulation of JAK-STAT cascade; negative regulation of JAK-STAT cascade; negative regulation of apoptotic process; negative regulation of inflammatory response; negative regulation of insulin receptor signaling pathway; negative regulation of protein kinase activity; negative regulation of signal transduction; placenta blood vessel development; positive regulation of cell differentiation; positive regulation of cell differentiation; regulation of cell differentiation; regulation of cell differentiation; regulation of growth; regulation of protein phosphorylation; signal transduction; spongiotrophoblast differentiation; spongiotrophoblast differentiation; trophoblast giant cell differentiation; trophoblast giant cell differentiation


cytoplasm; cytoplasm NM_007707. NM_007707 83 Exon

7690_DGP_17.T1

1-2

CDS

None

51/64


SRA1_80864_i1 Sra1

Entrez Gene ID

Assay ID 24068


Official Full Name steroid receptor RNA activator 1 Related IDs



Sra; Srap; Straa1; Strra1; AA959952 DNA binding; ligand-dependent nuclear receptor binding; ligand-dependent nuclear receptor transcription coactivator activity; ligand-dependent nuclear receptor transcription coactivator activity; thyroid hormone receptor activator activity; transcription coactivator activity; transcription cofactor activity

Go Process

cell differentiation; cell proliferation; positive regulation of transcription from RNA polymerase II promoter; regulation of apoptotic process; regulation of transcription from RNA polymerase II promoter cell leading edge; cytosol; intercellular bridge; intracellular ribonucleoprotein complex; microtubule cytoskeleton; nucleoplasm; nucleus; nucleus; plasma membrane; steroid hormone aporeceptor complex; transcription factor complex

Go Component

Gene Isoforms NM_025291.N; NM_001164406.N; NR_028355.N Blast Isoform Hits NM_001164406; NR_028355; NM_025291 Amplicon Length 86 Exon 2-3

7690_DGP_17.T1

CDS

Full

52/64


STAT1_80873_i21 Stat1

Entrez Gene ID

Assay ID 20846


Official Full Name signal transducer and activator of transcription 1 Related IDs



AA408197; 2010005J02Rik CCR5 chemokine receptor binding; DNA binding; RNA polymerase II core promoter proximal region sequencespecific DNA binding; RNA polymerase II core promoter sequence-specific DNA binding; cadherin binding; doublestranded DNA binding; enzyme binding; identical protein binding; nuclear hormone receptor binding; protein binding; protein homodimerization activity; protein phosphatase 2A binding; sequence-specific DNA binding; signal transducer activity; transcription factor activity, RNA polymerase II core promoter sequence-specific; transcription factor activity, sequence-specific DNA binding; transcription factor activity, sequence-specific DNA binding; tumor necrosis factor receptor binding Go Process JAK-STAT cascade; activation of cysteine-type endopeptidase activity involved in apoptotic process; blood circulation; cellular response to cytokine stimulus; cellular response to insulin stimulus; cellular response to interferon-beta; cellular response to lipopolysaccharide; cellular response to organic cyclic compound; cytokinemediated signaling pathway; interferon-gamma-mediated signaling pathway; interferon-gamma-mediated signaling pathway; lipopolysaccharide-mediated signaling pathway; macrophage derived foam cell differentiation; negative regulation by virus of viral protein levels in host cell; negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of angiogenesis; negative regulation of endothelial cell proliferation; negative regulation of macrophage fusion; positive regulation of cell proliferation; positive regulation of nitric-oxide synthase biosynthetic process; positive regulation of smooth muscle cell proliferation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-templated; regulation of transcription, DNA-templated; renal tubule development; response to bacterium; response to cAMP; response to cytokine; response to drug; response to exogenous dsRNA; response to interferon-beta; response to lipopolysaccharide; response to mechanical stimulus; response to nutrient; response to peptide hormone; response to type I interferon; signal transduction; transcription, DNA-templated; tumor necrosis factor-mediated signaling pathway; type I interferon signaling pathway Go Component axon; cytoplasm; cytoplasm; cytosol; dendrite; nuclear chromatin; nucleolus; nucleoplasm; nucleus; nucleus; perinuclear region of cytoplasm Gene Isoforms NM_001205314.; NM_009283.; NM_001205313. Blast Isoform Hits NM_001205314; NM_009283; NM_001205313 Amplicon Length 82 Exon 22-23 CDS Full

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STAT3_80877_i15 Stat3

Entrez Gene ID

Assay ID 20848


Official Full Name signal transducer and activator of transcription 3 Related IDs



Aprf; AW109958; 1110034C02Rik CCR5 chemokine receptor binding; DNA binding; DNA binding; RNA polymerase II core promoter proximal region sequence-specific DNA binding; RNA polymerase II repressing transcription factor binding; RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding; RNA polymerase II transcription factor activity, sequence-specific DNA binding; chromatin DNA binding; glucocorticoid receptor binding; identical protein binding; protein binding; protein dimerization activity; protein homodimerization activity; protein kinase binding; protein phosphatase binding; sequence-specific DNA binding; sequence-specific DNA binding; signal transducer activity; transcription factor activity, sequence-specific DNA binding; transcription factor activity, sequence-specific DNA binding; transcription factor binding; transcription regulatory region DNA binding; transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding

Go Process

JAK-STAT cascade; JAK-STAT cascade involved in growth hormone signaling pathway; JAK-STAT cascade involved in growth hormone signaling pathway; T-helper 17 cell lineage commitment; acute-phase response; astrocyte differentiation; cell proliferation; cellular response to cytokine stimulus; cellular response to hormone stimulus; cellular response to leptin stimulus; cellular response to organic cyclic compound; cytokine-mediated signaling pathway; eating behavior; energy homeostasis; eye photoreceptor cell differentiation; glucose homeostasis; growth hormone receptor signaling pathway; inflammatory response; interleukin-6-mediated signaling pathway; intracellular receptor signaling pathway; leptin-mediated signaling pathway; leptin-mediated signaling pathway; leptin-mediated signaling pathway; mRNA transcription from RNA polymerase II promoter; miRNA mediated inhibition of translation; negative regulation of apoptotic process; negative regulation of cell death; negative regulation of cell proliferation; negative regulation of glycolytic process; negative regulation of hydrogen peroxide biosynthetic process; negative regulation of neuron death; negative regulation of neuron migration; negative regulation of stem cell differentiation; phosphorylation; positive regulation of ATP biosynthetic process; positive regulation of Notch signaling pathway; positive regulation of cell proliferation; positive regulation of gene expression; positive regulation of gene expression; positive regulation of gene silencing by miRNA; positive regulation of growth factor dependent skeletal muscle satellite cell proliferation; positive regulation of metalloendopeptidase activity; positive regulation of pri-miRNA transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-templated; positive regulation of transcription, DNA-templated; positive regulation of transcription, DNA-templated; protein import into nucleus; radial glial cell differentiation; regulation of cell cycle; regulation of cell cycle; regulation of feeding behavior; regulation of mitochondrial membrane permeability; regulation of multicellular organism growth; regulation of transcription, DNA-templated; regulation of transcription, DNA-templated; response to cytokine; response to estradiol; response to leptin; response to leptin; response to leptin; sexual reproduction; signal transduction; stem cell population maintenance; temperature homeostasis; transcription from RNA polymerase II promoter; transcription, DNA-templated Go Component RNA polymerase II transcription factor complex; cytoplasm; cytoplasm; cytosol; mitochondrial inner membrane; mitochondrion; nuclear chromatin; nucleoplasm; nucleus; nucleus; plasma membrane Gene Isoforms NM_011486.; NM_213659.; NM_213660. Blast Isoform Hits NM_213659; NM_011486; NM_213660 Amplicon Length 77 Exon 16-17 CDS Full

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TGFB1_80819_i1 Tgfb1

Entrez Gene ID

Assay ID 21803


Official Full Name transforming growth factor, beta 1 Related IDs



Tgfb; Tgfb-1; TGFbeta1; TGF-beta1 antigen binding; cytokine activity; enzyme binding; glycoprotein binding; growth factor activity; protein Nterminus binding; protein binding; protein heterodimerization activity; protein homodimerization activity; protein serine/threonine kinase activator activity; transforming growth factor beta receptor binding; transforming growth factor beta receptor binding; type I transforming growth factor beta receptor binding; type II transforming growth factor beta receptor binding; type II transforming growth factor beta receptor binding; type III transforming growth factor beta receptor binding ATP biosynthetic process; BMP signaling pathway; CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment; MAPK cascade; Notch signaling pathway; SMAD protein complex assembly; SMAD protein import into nucleus; SMAD protein signal transduction; T cell activation; T cell activation; T cell differentiation; T cell homeostasis; T-helper 17 cell lineage commitment; adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains; animal organ morphogenesis; animal organ regeneration; branch elongation involved in mammary gland duct branching; cell activation; cell cycle arrest; cell growth; cell migration; cell proliferation; cell proliferation; cell-cell junction organization; cellular calcium ion homeostasis; cellular response to dexamethasone stimulus; cellular response to growth factor stimulus; cellular response to organic cyclic compound; cellular response to transforming growth factor beta stimulus; cellular response to transforming growth factor beta stimulus; chondrocyte differentiation; common-partner SMAD protein phosphorylation; defense response; defense response to fungus, incompatible interaction; embryonic liver development; endoderm development; epidermal growth factor receptor signaling pathway; epithelial to mesenchymal transition; evasion or tolerance of host defenses by virus; extracellular matrix assembly; extracellular matrix assembly; extrinsic apoptotic signaling pathway; face morphogenesis; germ cell migration; heart development; heart valve morphogenesis; hematopoietic progenitor cell differentiation; hyaluronan catabolic process; inflammatory response; inflammatory response; lens fiber cell differentiation; lipopolysaccharide-mediated signaling pathway; lymph node development; mammary gland branching involved in thelarche; mammary gland development; membrane protein intracellular domain proteolysis; mitotic cell cycle checkpoint; mononuclear cell proliferation; morphogenesis of a branching structure; myelination; myeloid dendritic cell differentiation; negative regulation of DNA replication; negative regulation of T cell activation; negative regulation of T cell proliferation; negative regulation of blood vessel endothelial cell migration; negative regulation of cell cycle; negative regulation of cell growth; negative regulation of cell growth; negative regulation of cell proliferation; negative regulation of cell proliferation; negative regulation of cell-cell adhesion; negative regulation of epithelial cell proliferation; negative regulation of fat cell differentiation; negative regulation of gene expression; negative regulation of gene silencing by miRNA; negative regulation of hyaluronan biosynthetic process; negative regulation of immune response; negative regulation of interleukin-17 production; negative regulation of macrophage cytokine production; negative regulation of mitotic cell cycle; negative regulation of myoblast differentiation; negative regulation of neuroblast proliferation; negative regulation of ossification; negative regulation of phagocytosis; negative regulation of production of miRNAs involved in gene silencing by miRNA; negative regulation of protein localization to plasma membrane; negative regulation of protein phosphorylation; negative regulation of release of sequestered calcium ion into cytosol; negative regulation of skeletal muscle tissue development; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-templated; neural tube closure; neural tube development; oligodendrocyte development; pathway-restricted SMAD protein phosphorylation; pathway-restricted SMAD protein phosphorylation; phosphate-containing compound metabolic process; positive regulation of ERK1 and ERK2 cascade; positive regulation of MAP kinase activity; positive regulation of NAD+ ADP-ribosyltransferase activity; positive regulation of NF-kappaB transcription factor activity; positive regulation of SMAD protein import into nucleus; positive regulation of apoptotic process; positive regulation of blood vessel endothelial cell migration; positive regulation of branching involved in ureteric bud morphogenesis; positive regulation of cardiac muscle cell differentiation; positive regulation of cell cycle arrest; positive regulation of cell division; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of cell proliferation; positive regulation of cellular protein metabolic process; positive regulation of chemotaxis; positive regulation of collagen biosynthetic process; positive regulation of collagen biosynthetic process; positive regulation of epithelial cell proliferation; positive regulation of epithelial to mesenchymal transition; positive regulation of epithelial to mesenchymal transition; positive regulation of exit from mitosis; positive regulation of fibroblast migration; positive regulation of fibroblast migration; positive regulation of fibroblast proliferation; positive regulation of gene expression; positive regulation of gene expression; positive regulation of histone acetylation; positive regulation of histone deacetylation; positive regulation of interleukin-17 production; positive regulation of interleukin-17 production; positive regulation of isotype switching to IgA isotypes; positive regulation of mononuclear cell migration; positive regulation of odontogenesis; positive regulation of pathway-restricted SMAD protein phosphorylation; positive regulation of pathway-restricted SMAD protein phosphorylation; positive regulation of peptidyl-serine phosphorylation; positive regulation of peptidylthreonine phosphorylation; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphatidylinositol 3-kinase activity; positive regulation of pri-miRNA transcription from RNA polymerase II promoter; positive regulation of production of miRNAs involved in gene silencing by miRNA; positive regulation of protein complex assembly; positive regulation of protein dephosphorylation; positive regulation of protein import into nucleus; positive regulation of protein kinase B signaling; positive regulation of protein localization to nucleus; positive regulation of protein phosphorylation; positive regulation of protein secretion; positive regulation of receptor clustering; positive regulation of regulatory T cell differentiation; positive regulation of smooth muscle cell differentiation; positive regulation of superoxide anion generation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription regulatory region DNA binding; positive regulation of transcription, DNA-templated; positive regulation of transcription, DNA-templated;

Go Process

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positive regulation of vascular permeability; protein export from nucleus; protein import into nucleus, translocation; protein kinase B signaling; protein phosphorylation; protein phosphorylation; protein phosphorylation; receptor catabolic process; regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation; regulation of DNA binding; regulation of MAPK cascade; regulation of SMAD protein import into nucleus; regulation of actin cytoskeleton reorganization; regulation of apoptotic process; regulation of binding; regulation of branching involved in mammary gland duct morphogenesis; regulation of cartilage development; regulation of cell proliferation; regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; regulation of gene expression; regulation of interleukin-23 production; regulation of protein import into nucleus; regulation of regulatory T cell differentiation; regulation of sodium ion transport; regulation of striated muscle tissue development; regulation of transforming growth factor beta receptor signaling pathway; regulatory T cell differentiation; regulatory T cell differentiation; response to cholesterol; response to estradiol; response to organic substance; response to progesterone; skeletal muscle tissue development; skeletal system development; tolerance induction to self antigen; transforming growth factor beta receptor signaling pathway; transforming growth factor beta receptor signaling pathway; transforming growth factor beta receptor signaling pathway involved in heart development; ureteric bud development; vasculogenesis; ventricular cardiac muscle tissue morphogenesis; wound healing Go Component

axon; blood microparticle; cell surface; cytoplasm; extracellular matrix; extracellular region; extracellular space; extracellular space; microvillus; neuronal cell body; nucleus; proteinaceous extracellular matrix; secretory granule Gene Isoforms NM_011577. Blast Isoform Hits NM_011577 Amplicon Length 82 Exon 2-3 CDS Full


TGM2_80882_i9 Tgm2

Entrez Gene ID

Assay ID 21817


Official Full Name transglutaminase 2, C polypeptide Related IDs



TG2; tTG; G[a]h; tTGas; TGase2 GTP binding; GTP binding; calcium ion binding; metal ion binding; protein domain specific binding; proteinglutamine gamma-glutamyltransferase activity; protein-glutamine gamma-glutamyltransferase activity; transaminase activity; transferase activity; transferase activity, transferring acyl groups

Go Process

G-protein coupled receptor signaling pathway; apoptotic cell clearance; blood vessel remodeling; branching involved in salivary gland morphogenesis; isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine; negative regulation of endoplasmic reticulum calcium ion concentration; negative regulation of endoplasmic reticulum calcium ion concentration; peptide cross-linking; phospholipase C-activating G-protein coupled receptor signaling pathway; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of apoptotic process; positive regulation of cell adhesion; positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway; positive regulation of inflammatory response; positive regulation of mitochondrial calcium ion concentration; positive regulation of mitochondrial calcium ion concentration; positive regulation of smooth muscle cell proliferation; protein homooligomerization; salivary gland cavitation

Go Component

cytoplasm; cytosol; cytosol; extracellular exosome; extracellular matrix; focal adhesion; intrinsic component of plasma membrane; membrane; mitochondrion; plasma membrane; proteinaceous extracellular matrix Gene Isoforms NM_009373. Blast Isoform Hits NM_009373 Amplicon Length 89 Exon 10-11 CDS Full

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TLR8_80891_i0 Tlr8

Entrez Gene ID

Assay ID 170744


Official Full Name toll-like receptor 8 Related IDs Also known as GO Function Go Process

MGI:MGI:2176887; Ensembl:ENSMUSG00000040522; Vega:OTTMUSG00000019575 DNA binding; double-stranded RNA binding; drug binding; protein binding; receptor activity; single-stranded RNA binding I-kappaB kinase/NF-kappaB signaling; MyD88-dependent toll-like receptor signaling pathway; defense response to virus; immune system process; inflammatory response; innate immune response; microglial cell activation; negative regulation of interleukin-12 secretion; positive regulation of innate immune response; positive regulation of interferon-alpha biosynthetic process; positive regulation of interferon-beta biosynthetic process; positive regulation of interferon-gamma biosynthetic process; positive regulation of interleukin-1 beta secretion; positive regulation of interleukin-6 secretion; positive regulation of interleukin-8 biosynthetic process; regulation of cytokine secretion; regulation of protein phosphorylation; response to virus; signal transduction; toll-like receptor 8 signaling pathway; toll-like receptor signaling pathway; toll-like receptor signaling pathway

Go Component

external side of plasma membrane; integral component of membrane; integral component of plasma membrane; membrane Gene Isoforms NM_001313760.N; NM_001313761.N; NM_133212.N Blast Isoform Hits NM_001313761; NM_001313760 Amplicon Length 76 Exon 1-2 CDS None

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TLR9_80883_i0 Tlr9

Entrez Gene ID

Assay ID 81897


Official Full Name toll-like receptor 9 Related IDs Also known as GO Function Go Process

Go Component

MGI:MGI:1932389; Ensembl:ENSMUSG00000045322; Vega:OTTMUSG00000049422 interleukin-1 receptor binding; interleukin-1 receptor binding; protein binding; siRNA binding; transmembrane signaling receptor activity; unmethylated CpG binding I-kappaB phosphorylation; MyD88-dependent toll-like receptor signaling pathway; axonogenesis; cellular response to chloroquine; defense response to Gram-negative bacterium; defense response to virus; defense response to virus; immune response; immune system process; inflammatory response; innate immune response; maintenance of gastrointestinal epithelium; microglial cell activation; negative regulation of NF-kappaB transcription factor activity; negative regulation of calcium-transporting ATPase activity; negative regulation of interleukin-6 production; negative regulation of interleukin-8 production; negative regulation of toll-like receptor signaling pathway; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of JUN kinase activity; positive regulation of NF-kappaB import into nucleus; positive regulation of NF-kappaB transcription factor activity; positive regulation of autophagy; positive regulation of chemokine production; positive regulation of gene expression; positive regulation of granulocyte macrophage colony-stimulating factor production; positive regulation of inflammatory response; positive regulation of interferon-alpha biosynthetic process; positive regulation of interferon-beta biosynthetic process; positive regulation of interferon-beta production; positive regulation of interferon-gamma biosynthetic process; positive regulation of interleukin-10 production; positive regulation of interleukin-12 production; positive regulation of interleukin-18 production; positive regulation of interleukin-6 production; positive regulation of interleukin-6 production; positive regulation of interleukin-8 production; positive regulation of nitric-oxide synthase biosynthetic process; positive regulation of toll-like receptor signaling pathway; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of tumor necrosis factor production; regulation of B cell activation; regulation of cytokine secretion; regulation of dendritic cell cytokine production; regulation of inflammatory response; regulation of protein phosphorylation; response to molecule of bacterial origin; response to virus; signal transduction; toll-like receptor 9 signaling pathway; toll-like receptor signaling pathway; toll-like receptor signaling pathway; tumor necrosis factor production apical plasma membrane; basolateral plasma membrane; cytoplasm; cytoplasmic vesicle; early phagosome; endoplasmic reticulum; endosome; extracellular space; integral component of membrane; lysosome; membrane; plasma membrane; plasma membrane; plasma membrane; proteinaceous extracellular matrix

Gene Isoforms NM_031178.N Blast Isoform Hits NM_031178 Amplicon Length 73

7690_DGP_17.T1

Exon

1-2

CDS

Partial

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TNF_59464_i0 Tnf

Entrez Gene ID

Assay ID 21926


Official Full Name tumor necrosis factor Related IDs



DIF; Tnfa; TNF-a; TNFSF2; Tnlg1f; Tnfsf1a; TNFalpha; TNF-alpha cytokine activity; cytokine activity; identical protein binding; protease binding; protease binding; protein binding; transcription regulatory region DNA binding; tumor necrosis factor receptor binding; tumor necrosis factor receptor binding; tumor necrosis factor receptor binding; tumor necrosis factor receptor binding

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Go Process

JNK cascade; MAPK cascade; activation of MAPK activity; activation of MAPKKK activity; activation of cysteine-type endopeptidase activity involved in apoptotic process; activation of cysteine-type endopeptidase activity involved in apoptotic process; animal organ morphogenesis; apoptotic process; apoptotic signaling pathway; calciummediated signaling; cell activation; cell proliferation; cellular extravasation; cellular response to amino acid stimulus; cellular response to lipopolysaccharide; cellular response to nicotine; cellular response to organic cyclic compound; chronic inflammatory response to antigenic stimulus; cortical actin cytoskeleton organization; defense response; defense response to Gram-positive bacterium; defense response to bacterium; detection of mechanical stimulus involved in sensory perception of pain; endothelial cell apoptotic process; epithelial cell proliferation involved in salivary gland morphogenesis; establishment of protein localization to plasma membrane; extracellular matrix organization; extrinsic apoptotic signaling pathway; extrinsic apoptotic signaling pathway; extrinsic apoptotic signaling pathway via death domain receptors; extrinsic apoptotic signaling pathway via death domain receptors; glucose metabolic process; humoral immune response; immune response; inflammatory response; inflammatory response; inflammatory response; intrinsic apoptotic signaling pathway in response to DNA damage; leukocyte migration; leukocyte tethering or rolling; lipopolysaccharide-mediated signaling pathway; multicellular organism development; necroptotic signaling pathway; necroptotic signaling pathway; negative regulation of Lglutamate transport; negative regulation of alkaline phosphatase activity; negative regulation of bicellular tight junction assembly; negative regulation of branching involved in lung morphogenesis; negative regulation of cell proliferation; negative regulation of cytokine secretion involved in immune response; negative regulation of endothelial cell proliferation; negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; negative regulation of gene expression; negative regulation of glucose import; negative regulation of glucose import; negative regulation of growth of symbiont in host; negative regulation of interleukin-6 production; negative regulation of lipid catabolic process; negative regulation of mitotic cell cycle; negative regulation of myelination; negative regulation of myoblast differentiation; negative regulation of myosin-light-chainphosphatase activity; negative regulation of osteoblast differentiation; negative regulation of protein complex disassembly; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-templated; negative regulation of viral genome replication; osteoclast differentiation; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of I-kappaB kinase/NFkappaB signaling; positive regulation of JNK cascade; positive regulation of JNK cascade; positive regulation of JUN kinase activity; positive regulation of MAP kinase activity; positive regulation of NF-kappaB import into nucleus; positive regulation of NF-kappaB import into nucleus; positive regulation of NF-kappaB transcription factor activity; positive regulation of NFAT protein import into nucleus; positive regulation of NIK/NF-kappaB signaling; positive regulation of action potential; positive regulation of apoptotic process; positive regulation of blood microparticle formation; positive regulation of calcidiol 1-monooxygenase activity; positive regulation of cell adhesion; positive regulation of cell proliferation; positive regulation of chemokine (C-X-C motif) ligand 2 production; positive regulation of chemokine biosynthetic process; positive regulation of chemokine production; positive regulation of chronic inflammatory response to antigenic stimulus; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; positive regulation of cytokine production; positive regulation of cytokine secretion; positive regulation of fever generation; positive regulation of gene expression; positive regulation of hair follicle development; positive regulation of heterotypic cell-cell adhesion; positive regulation of heterotypic cell-cell adhesion; positive regulation of humoral immune response mediated by circulating immunoglobulin; positive regulation of inflammatory response; positive regulation of interferon-gamma production; positive regulation of interleukin-18 production; positive regulation of interleukin-6 production; positive regulation of interleukin-8 biosynthetic process; positive regulation of interleukin-8 production; positive regulation of leukocyte adhesion to arterial endothelial cell; positive regulation of leukocyte adhesion to vascular endothelial cell; positive regulation of membrane protein ectodomain proteolysis; positive regulation of mitotic nuclear division; positive regulation of neuron apoptotic process; positive regulation of nitric oxide biosynthetic process; positive regulation of osteoclast differentiation; positive regulation of peptidyl-serine phosphorylation; positive regulation of phagocytosis; positive regulation of podosome assembly; positive regulation of programmed cell death; positive regulation of protein complex assembly; positive regulation of protein complex disassembly; positive regulation of protein kinase B signaling; positive regulation of protein kinase activity; positive regulation of protein localization to cell surface; positive regulation of protein phosphorylation; positive regulation of protein transport; positive regulation of sequence-specific DNA binding transcription factor activity; positive regulation of smooth muscle cell proliferation; positive regulation of superoxide dismutase activity; positive regulation of synaptic transmission; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-templated; positive regulation of transcription, DNA-templated; positive regulation of translational initiation by iron; positive regulation of vascular smooth muscle cell proliferation; positive regulation of vitamin D biosynthetic process; protein import into nucleus, translocation; protein kinase B signaling; receptor biosynthetic process; regulation of I-kappaB kinase/NF-kappaB signaling; regulation of branching involved in salivary gland morphogenesis; regulation of branching involved in salivary gland morphogenesis; regulation of cell proliferation; regulation of establishment of endothelial barrier; regulation of immunoglobulin secretion; regulation of insulin secretion; regulation of osteoclast differentiation; regulation of protein phosphorylation; regulation of protein secretion; regulation of reactive oxygen species metabolic process; response to glucocorticoid; response to lipopolysaccharide; response to organic substance; response to virus; sequestering of triglyceride; signal transduction; toll-like receptor 3 signaling pathway; tumor necrosis factor-mediated signaling pathway; tumor necrosis factor-mediated signaling pathway Go Component cell surface; external side of plasma membrane; extracellular region; extracellular space; extracellular space; integral component of membrane; integral component of plasma membrane; integral component of plasma membrane; intracellular; membrane; membrane raft; membrane raft; phagocytic cup; plasma membrane; recycling endosome; secretory granule Gene Isoforms NM_013693.; NM_001278601. Blast Isoform Hits NM_001278601.1; NM_013693.3 Amplicon Length 75 Exon 1-2 CDS Full

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TNFRSF10B_80830_i6 Tnfrsf10b

Entrez Gene ID

Assay ID 21933


Official Full Name tumor necrosis factor receptor superfamily, member 10b Related IDs



MK; DR5; Ly98; KILLER; TRICKB; TRAILR2; TRICK2A; TRICK2B TRAIL binding; cysteine-type endopeptidase activator activity involved in apoptotic process; protease binding; transcription factor binding; tumor necrosis factor-activated receptor activity Go Process TRAIL-activated apoptotic signaling pathway; apoptotic process; apoptotic signaling pathway; extrinsic apoptotic signaling pathway; extrinsic apoptotic signaling pathway via death domain receptors; immune response; inflammatory response; multicellular organism development; regulation of apoptotic process; regulation of apoptotic process; regulation of cell proliferation; response to lipopolysaccharide; signal transduction Go Component cell surface; integral component of membrane; integral component of plasma membrane; membrane Gene Isoforms NM_020275. Blast Isoform Hits NM_020275 Amplicon Length 82 Exon 7-8 CDS Full

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TNFSF11_79030_i3 Tnfsf11

Entrez Gene ID

Assay ID 21943


Official Full Name tumor necrosis factor (ligand) superfamily, member 11 Related IDs



ODF; OPGL; RANKL; Ly109l; Trance cytokine activity; protein binding; tumor necrosis factor receptor binding; tumor necrosis factor receptor superfamily binding Go Process ERK1 and ERK2 cascade; TNFSF11-mediated signaling pathway; TNFSF11-mediated signaling pathway; activation of JUN kinase activity; animal organ morphogenesis; bone resorption; calcium ion homeostasis; calcium-mediated signaling; cell differentiation; cytokine-mediated signaling pathway; immune response; lymph node development; mammary gland alveolus development; mammary gland epithelial cell proliferation; monocyte chemotaxis; multicellular organism development; ossification; osteoclast differentiation; osteoclast differentiation; osteoclast differentiation; osteoclast differentiation; osteoclast proliferation; paracrine signaling; positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of JNK cascade; positive regulation of MAP kinase activity; positive regulation of NF-kappaB transcription factor activity; positive regulation of T cell activation; positive regulation of bone resorption; positive regulation of corticotropin-releasing hormone secretion; positive regulation of fever generation by positive regulation of prostaglandin secretion; positive regulation of homotypic cell-cell adhesion; positive regulation of intracellular signal transduction; positive regulation of osteoclast development; positive regulation of osteoclast differentiation; positive regulation of osteoclast differentiation; positive regulation of osteoclast differentiation; positive regulation of phosphorylation; positive regulation of protein kinase B signaling; positive regulation of sequence-specific DNA binding transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; protein homooligomerization; regulation of osteoclast differentiation; tumor necrosis factor-mediated signaling pathway Go Component cytoplasm; extracellular region; extracellular space; integral component of membrane; membrane; plasma membrane Gene Isoforms NM_011613. Blast Isoform Hits NM_011613 Amplicon Length 79 Exon 4-5 CDS Full

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VEGFA_80825_i3 Vegfa

Entrez Gene ID

Assay ID 22339


Official Full Name vascular endothelial growth factor A Related IDs



Vpf; Vegf chemoattractant activity; chemoattractant activity; cytokine activity; extracellular matrix binding; fibronectin binding; growth factor activity; growth factor activity; growth factor binding; heparin binding; heparin binding; identical protein binding; neuropilin binding; platelet-derived growth factor receptor binding; protein binding; protein heterodimerization activity; protein homodimerization activity; receptor agonist activity; receptor binding; vascular endothelial growth factor receptor 1 binding; vascular endothelial growth factor receptor 1 binding; vascular endothelial growth factor receptor 2 binding; vascular endothelial growth factor receptor 2 binding; vascular endothelial growth factor receptor 2 binding; vascular endothelial growth factor receptor binding T-helper 1 type immune response; VEGF-activated neuropilin signaling pathway; activation of protein kinase activity; angiogenesis; angiogenesis; angiogenesis; angiogenesis; angiogenesis involved in coronary vascular morphogenesis; artery morphogenesis; basophil chemotaxis; blood vessel development; blood vessel endothelial cell proliferation involved in sprouting angiogenesis; blood vessel morphogenesis; blood vessel morphogenesis; blood vessel morphogenesis; blood vessel remodeling; bone trabecula formation; bone trabecula morphogenesis; branching involved in blood vessel morphogenesis; branching morphogenesis of an epithelial tube; camera-type eye morphogenesis; cardiac muscle fiber development; cardiac vascular smooth muscle cell development; cell chemotaxis; cell differentiation; cell maturation; cell migration; cell migration; cell migration involved in sprouting angiogenesis; cell proliferation; cellular response to hypoxia; cellular response to vascular endothelial growth factor stimulus; cellular response to vascular endothelial growth factor stimulus; commissural neuron axon guidance; commissural neuron axon guidance; commissural neuron axon guidance; coronary artery morphogenesis; coronary vein morphogenesis; dopaminergic neuron differentiation; endothelial cell chemotaxis; endothelial cell migration; epithelial cell differentiation; eye photoreceptor cell development; growth; heart morphogenesis; homeostasis of number of cells within a tissue; in utero embryonic development; induction of positive chemotaxis; induction of positive chemotaxis; kidney development; lactation; lung alveolus development; lung development; lung development; lung vasculature development; lung vasculature development; lymph vessel morphogenesis; lymphangiogenesis; mRNA stabilization; macrophage differentiation; mammary gland alveolus development; mesoderm development; monocyte differentiation; motor neuron migration; multicellular organism development; negative regulation of apoptotic process; negative regulation of apoptotic process; negative regulation of bone resorption; negative regulation of cell-cell adhesion; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of extrinsic apoptotic signaling pathway; negative regulation of fat cell differentiation; negative regulation of gene expression; negative regulation of neuron apoptotic process; negative regulation of neuron death; negative regulation of programmed cell death; negative regulation of transcription from RNA polymerase II promoter; nervous system development; neuron development; outflow tract morphogenesis; ovarian follicle development; positive chemotaxis; positive chemotaxis; positive regulation of CREB transcription factor activity; positive regulation of ERK1 and ERK2 cascade; positive regulation of ERK1 and ERK2 cascade; positive regulation of MAP kinase activity; positive regulation of angiogenesis; positive regulation of angiogenesis; positive regulation of axon extension involved in axon guidance; positive regulation of axon extension involved in axon guidance; positive regulation of axon extension involved in axon guidance; positive regulation of blood vessel endothelial cell migration; positive regulation of branching involved in ureteric bud morphogenesis; positive regulation of cell adhesion; positive regulation of cell division; positive regulation of cell migration; positive regulation of cell migration involved in sprouting angiogenesis; positive regulation of cell proliferation; positive regulation of cell proliferation; positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway; positive regulation of cellular component movement; positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway; positive regulation of endothelial cell migration; positive regulation of endothelial cell proliferation; positive regulation of endothelial cell proliferation; positive regulation of epithelial cell proliferation; positive regulation of focal adhesion assembly; positive regulation of gene expression; positive regulation of histone deacetylase activity; positive regulation of lymphangiogenesis; positive regulation of mast cell chemotaxis; positive regulation of mast cell chemotaxis; positive regulation of mesenchymal cell proliferation; positive regulation of neuroblast proliferation; positive regulation of osteoblast differentiation; positive regulation of p38MAPK cascade; positive regulation of peptidyl-serine phosphorylation; positive regulation of peptidyl-tyrosine autophosphorylation; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of peptidyltyrosine phosphorylation; positive regulation of positive chemotaxis; positive regulation of protein autophosphorylation; positive regulation of protein complex assembly; positive regulation of protein kinase B signaling; positive regulation of protein kinase C signaling; positive regulation of protein kinase D signaling; positive regulation of protein localization to early endosome; positive regulation of protein phosphorylation; positive regulation of receptor internalization; positive regulation of retinal ganglion cell axon guidance; positive regulation of signal transduction; positive regulation of smooth muscle cell proliferation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; positive regulation of vascular endothelial growth factor receptor signaling pathway; positive regulation of vascular permeability; positive regulation of vascular permeability; post-embryonic camera-type eye development; primitive erythrocyte differentiation; regulation of cGMP metabolic process; regulation of cell shape; regulation of endothelial cell differentiation; regulation of hematopoietic progenitor cell differentiation; regulation of retinal ganglion cell axon guidance; regulation of retinal ganglion cell axon guidance; regulation of retinal ganglion cell axon guidance; regulation of transcription from RNA polymerase II promoter; response to hypoxia; response to hypoxia; retinal blood vessel morphogenesis; sprouting angiogenesis; surfactant homeostasis; tube formation; vascular endothelial growth factor receptor signaling pathway; vascular endothelial growth factor receptor signaling pathway; vascular endothelial growth factor signaling pathway; vascular endothelial growth factor signaling pathway; vasculature development

Go Process

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Go Component

basement membrane; cell surface; cytoplasm; cytoplasm; extracellular region; extracellular space; extracellular space; membrane; nucleus; plasma membrane; secretory granule; vesicle Gene Isoforms NM_001025250.; NM_001287056.; NM_001110267.; NM_001025257.; NM_001110266.; NM_009505.; NM_001287057.; NM_001110268.; NM_001287058.; NM_001317041. Blast Isoform Hits NM_001025250; NM_001287056; NM_001110266; NM_001025257; NM_001110268; NM_001287058; NM_009505; NM_001287057; NM_001110267; NM_001317041 Amplicon Length 77 Exon 4-5 CDS Full


XIAP_80881_i2 Xiap

Entrez Gene ID

Assay ID 11798


Official Full Name X-linked inhibitor of apoptosis Related IDs



Aipa; Api3; IAP3; MIHA; Birc4; ILP-1; 1110015C02Rik cysteine-type endopeptidase inhibitor activity involved in apoptotic process; cysteine-type endopeptidase inhibitor activity involved in apoptotic process; identical protein binding; metal ion binding; protease binding; protein binding; scaffold protein binding; transferase activity; ubiquitin protein ligase activity; ubiquitin-protein transferase activity; ubiquitin-protein transferase activity; zinc ion binding Go Process Wnt signaling pathway; apoptotic process; inhibition of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of apoptotic process; negative regulation of apoptotic process; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of neuron apoptotic process; neuron apoptotic process; positive regulation of canonical Wnt signaling pathway; positive regulation of canonical Wnt signaling pathway; positive regulation of protein linear polyubiquitination; positive regulation of protein ubiquitination Go Component cytoplasm; cytoplasm; cytosol; nucleus; nucleus; perinuclear region of cytoplasm; protein complex Gene Isoforms NR_125870.N; NM_009688.N; NM_001301641.N; NM_001301639.N Blast Isoform Hits NM_001301639; NM_001301641; NR_125870; NM_009688 Amplicon Length 77 Exon 3-4 CDS Full

7690_DGP_17.T1

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Myelolytic Treatments Enhance Oncolytic Herpes Virotherapy in

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