IRS1

Chr 2AD

insulin receptor substrate 1

Also known as: HIRS-1

NCBI Gene: 3667 ENSG00000169047 UniProt: P35568 OMIM: 147545

The insulin receptor substrate 1 protein serves as a signaling adapter that is phosphorylated by insulin and insulin-like growth factor I receptors, functioning as a scaffold to propagate downstream signaling pathways critical for glucose homeostasis, lipid metabolism, growth, and development. Mutations cause autosomal dominant susceptibility to type 2 diabetes mellitus and insulin resistance. This gene is not highly constrained against loss-of-function variants, consistent with its role in disease susceptibility rather than severe developmental disorders.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene are associated with type II diabetes and susceptibility to insulin resistance. [provided by RefSeq, Nov 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Type 2 diabetes mellitus, susceptibility to}MIM #125853

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

274

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

Multiple*

Mechanism· predicted