ITGAE
Chr 17integrin subunit alpha E
Also known as: CD103, HUMINAE
The ITGAE protein is an integrin alpha subunit that pairs with integrin beta-7 to form a receptor for E-cadherin, mediating adhesion of intraepithelial T-lymphocytes to epithelial cells in the intestinal mucosa. Mutations in ITGAE cause autosomal recessive inflammatory bowel disease, typically presenting in infancy or early childhood with severe diarrhea and intestinal inflammation. The gene shows tolerance to loss-of-function variants in the general population, suggesting that biallelic mutations are required for disease manifestation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
435 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 | 31 | 0 | 31 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 309 | 19 | 0 | 328 |
Likely Benign | 0 | 31 | 3 | 5 | 39 |
Benign | 0 | 1 | 1 | 0 | 2 |
Conflicting | — | 1 | |||
| Total | 0 | 341 | 55 | 5 | 402 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ITGAE · 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