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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.
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.
Open 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.
In plain words · 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.
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.
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.
No product in this corpus aims at IRS4 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
First described 1997. Earliest sequence paper UniProt cites for the protein: Lavan B.E. et al, J. Biol. Chem, 1997, "A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells is a new member of the insulin receptor substrate family". Source.
Sources: HGNC HGNC:6128 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O14654 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000133124 (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)); IntOGen IRS4 (driver in 2 cohorts (Act 1, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
Query for this target: (TITLE:"IRS4" OR ABSTRACT:"IRS4" OR TITLE:"insulin receptor substrate 4" OR ABSTRACT:"insulin receptor substrate 4" OR TITLE:"Insulin receptor substrate 4" OR ABSTRACT:"Insulin receptor substrate 4" OR TITLE:"PY160" OR ABSTRACT:"PY160" OR TITLE:"IRS-4" OR ABSTRACT:"IRS-4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about IRS4, not a curated reading list.