IRS2

Chr 13AD

insulin receptor substrate 2

Also known as: IRS-2

This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an interleukin 4 receptor-associated kinase in response to IL4 treatment. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Diabetes mellitus, noninsulin-dependent}MIM #125853
AD
0
Active trials
70
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.29
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryIRS2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.990
Z-score 4.30
OE 0.11 (0.050.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.53Z-score
OE missense 0.74 (0.690.79)
541 obs / 733.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.11 (0.050.29)
00.351.4
Missense OE0.74 (0.690.79)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 3 / 27.2Missense obs/exp: 541 / 733.8Syn Z: -0.78
DN
0.3594th %ile
GOF
0.3491th %ile
LOF
0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗