IRS2
Chr 13ADinsulin receptor substrate 2
Also known as: IRS-2
The insulin receptor substrate 2 protein functions as a cytoplasmic signaling adapter that mediates insulin and insulin-like growth factor 1 signaling by connecting receptor tyrosine kinases to downstream effectors in pathways controlling glucose homeostasis, lipid metabolism, and cell growth. Mutations cause autosomal dominant noninsulin-dependent diabetes mellitus. This gene is highly constrained against loss-of-function variants (pLI 0.99), indicating that complete loss of protein function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
IRS2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools