IRS4
Chr XXLRinsulin receptor substrate 4
Also known as: CHNG9, IRS-4, PY160
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.
Primary Disease Associations & Inheritance
Some data sources returned errors (1)
gnomad: TimeoutError: The operation was aborted due to timeout
Population Genetics & Constraint
Constraint data not available from gnomAD.
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
243 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 79 | 0 | 79 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 1 | 131 | 4 | 0 | 136 |
Likely Benign | 0 | 13 | 0 | 6 | 19 |
Benign | 0 | 2 | 0 | 1 | 3 |
Conflicting | — | 2 | |||
| Total | 1 | 146 | 86 | 7 | 242 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
IRS4 · 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