{"entity":{"id":"irs2","kind":"target","name":"IRS2","aka":["insulin receptor substrate 2","Insulin receptor substrate 2"],"tldr":"IRS2 (Insulin receptor substrate 2) is a gene. The public catalogues list it as a drug target and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer and Prostate cancer.","summary":"Signalling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R. Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism. Upon phosphorylation by the insulin receptor, functions as a signalling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2.\n\nCIViC holds 2 clinical evidence items and 0 assertions across 1 variant, naming Capivasertib and Dual IGF-1R/InsR Inhibitor BMS-754807. Open Targets scores its association with cancer at 0.56 (direct and indirect evidence; datatypes literature 0.93, affected pathway 0.54, animal model 0.78, genetic association 0.58).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:6126","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6126"},{"label":"UniProt Q9Y4H2","url":"https://www.uniprot.org/uniprotkb/Q9Y4H2/entry"},{"label":"NCBI Gene 8660","url":"https://www.ncbi.nlm.nih.gov/gene/8660"},{"label":"Ensembl ENSG00000185950","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000185950"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets"],"cancers":["colorectal","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 2 therapies; CIViC holds 2 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"IRS2","role":["drug-target","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:6126","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6126","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9Y4H2","url":"https://www.uniprot.org/uniprotkb/Q9Y4H2/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene IRS2","url":"https://civicdb.org/features/6862","note":"2 evidence items, 0 assertions, 1 variants; diseases: Colorectal Cancer, Prostate Cancer (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000185950","url":"https://platform.opentargets.org/target/ENSG00000185950/associations","note":"association with cancer (MONDO_0004992) 0.56;  (GraphQL API, CC0)"}],"distribution":"few-types","specificityNote":"Specificity not established: no corpus medicine is aimed at it and the catalogues give it only the roles drug-target, biomarker; HPA finds the RNA tissue enhanced, which says where the protein sits but not whether the tumour differs from normal tissue. HPA IRS2: RNA tissue enhanced (bone marrow 48 nTPM); blood lineage lineage enriched (granulocytes 3 nTPM); high antibody staining in 1 normal tissue. Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Prostate cancer); Open Targets associates it with 0 specific cancer types at or above 0.5. (No rule of scripts/fetch-target-specificity.ts fired.)","specificitySources":[{"label":"Human Protein Atlas IRS2 tissue","url":"https://www.proteinatlas.org/ENSG00000185950-IRS2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000185950 associations","url":"https://platform.opentargets.org/target/ENSG00000185950/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:6126","ensembl":"ENSG00000185950","uniprot":"Q9Y4H2","entrez":"8660","firstDescribed":1997,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Ogihara et al, J. Biol. Chem, 1997, \"14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9312143/","biology":"Signalling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R. Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism. Upon phosphorylation by the insulin receptor, functions as a signalling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2. Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signalling cascade. Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signalling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation. Location: Cytoplasm, cytosol (UniProt). Locus 13q34 (HGNC).","whereFound":["Colorectal cancer: CIViC evidence names this disease","Prostate cancer: CIViC evidence names this disease"],"targetClass":"other","prevalence":[]},"route":"/targets/irs2/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}]}}