IRS4
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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).
External identifiers
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)
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).
- 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)
Notes
top- 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.
Latest papers
topQuery 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.
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