# IRS2

Source: https://onco.cc/targets/irs2/  
OnCo record `irs2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: insulin receptor substrate 2; Insulin receptor substrate 2
- Tags: cancer-genes-wave
- Symbol: IRS2
- Class: other
- 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).
- Where found: Colorectal cancer: CIViC evidence names this disease; Prostate cancer: CIViC evidence names this disease

## 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.

## Sources

- HGNC HGNC:6126: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6126
- UniProt Q9Y4H2: https://www.uniprot.org/uniprotkb/Q9Y4H2/entry
- NCBI Gene 8660: https://www.ncbi.nlm.nih.gov/gene/8660
- Ensembl ENSG00000185950: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000185950

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Prostate cancer](https://onco.cc/cancers/prostate/)

---
JSON: https://onco.cc/api/v1/entities/irs2.json