IRS4

Chr XXLR

insulin receptor substrate 4

Also known as: CHNG9, IRS-4, PY160

NCBI Gene: 8471 ENSG00000133124 UniProt: O14654 OMIM: 300904

IRS4 encodes insulin receptor substrate 4, a cytoplasmic signaling protein that serves as an interface between growth factor receptors (including insulin, IGF1, and FGFR1 receptors) and downstream SH2 domain-containing signaling molecules involved in growth, reproduction, and glucose homeostasis. Mutations cause congenital nongoitrous hypothyroidism type 9 with X-linked recessive inheritance. The gene shows significant constraint against loss-of-function variants (LOEUF 0.43), suggesting intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

IRS4 encodes the insulin receptor substrate 4, a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyrosine-phosphorylated IRS4 protein has been shown to associate with cytoplasmic signalling molecules that contain SH2 domains. The IRS4 protein is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation.. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hypothyroidism, congenital, nongoitrous, 9MIM #301035

XLR

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

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.43

LOEUF

LOF

Mechanism· predicted