{"entity":{"id":"irs4","kind":"target","name":"IRS4","aka":["insulin receptor substrate 4","Insulin receptor substrate 4","PY160","IRS-4"],"tldr":"IRS4 (Insulin receptor substrate 4) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Bladder & urothelial cancer, Pancreatic ductal adenocarcinoma, Colorectal cancer and 4 more.","summary":"Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signalling molecules containing SH2 domains. Involved in the IGF1R mitogenic signalling pathway. Promotes the AKT1 signalling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis.\n\nOpen Targets scores its association with cancer at 0.64 (direct and indirect evidence; datatypes literature 0.93, somatic mutation 0.83). IntOGen calls it a driver in 2 cohorts (1 activating, 1 loss-of-function), covering Bladder Urothelial Carcinoma, Pancreatic Adenocarcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:6128","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6128"},{"label":"UniProt O14654","url":"https://www.uniprot.org/uniprotkb/O14654/entry"},{"label":"NCBI Gene 8471","url":"https://www.ncbi.nlm.nih.gov/gene/8471"},{"label":"Ensembl ENSG00000133124","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000133124"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["urothelial","pancreatic","colorectal","lung-cancer","skin-cancer","melanoma","nsclc"],"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: IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier \"cohort-driver\" 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":"IRS4","role":["oncogene-driver","tumour-suppressor"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:6128","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6128","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt O14654","url":"https://www.uniprot.org/uniprotkb/O14654/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000133124","url":"https://platform.opentargets.org/target/ENSG00000133124/associations","note":"association with cancer (MONDO_0004992) 0.64; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.50, colorectal cancer 0.53, melanoma 0.53, skin cancer 0.51, lung cancer 0.52 (GraphQL API, CC0)"},{"label":"IntOGen IRS4","url":"https://www.intogen.org/search?gene=IRS4","note":"driver in 2 cohorts (Act 1, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:6128","ensembl":"ENSG00000133124","uniprot":"O14654","entrez":"8471","biology":"Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signalling molecules containing SH2 domains. Involved in the IGF1R mitogenic signalling pathway. Promotes the AKT1 signalling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signalling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. Location: Cell membrane (UniProt). Locus Xq22.3 (HGNC).","whereFound":["Bladder & urothelial cancer: IntOGen driver in 1 cohort (BLCA)","Pancreatic ductal adenocarcinoma: IntOGen driver in 1 cohort (PAAD)","Colorectal cancer: Open Targets association 0.53 with colorectal cancer (MONDO_0005575)","Lung cancer: Open Targets association 0.52 with lung cancer (MONDO_0008903)","Skin cancer: Open Targets association 0.51 with skin cancer (MONDO_0002898)","Melanoma: Open Targets association 0.53 with melanoma (MONDO_0005105)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/irs4/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}]}}