ITGAE

Chr 17

integrin subunit alpha E

Also known as: CD103, HUMINAE

NCBI Gene: 3682ENSG00000083457UniProt: P38570

Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This gene encodes an I-domain-containing alpha integrin that undergoes post-translational cleavage in the extracellular domain, yielding disulfide-linked heavy and light chains. In combination with the beta 7 integrin, this protein forms the E-cadherin binding integrin known as the human mucosal lymphocyte-1 antigen. This protein is preferentially expressed in human intestinal intraepithelial lymphocytes (IEL), and in addition to a role in adhesion, it may serve as an accessory molecule for IEL activation. [provided by RefSeq, Jul 2008]

167
ClinVar variants
9
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ITGAE
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 136 VUS of 167 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.88LOEUF
pLI 0.000
Z-score 2.28
OE 0.68 (0.53–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.24Z-score
OE missense 0.97 (0.91–1.04)
676 obs / 693.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.68 (0.53–0.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.91–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 40 / 58.9Missense obs/exp: 676 / 693.5Syn Z: 0.80

ClinVar Variant Classifications

167 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
VUS136
Likely Benign20
Benign2
9
Pathogenic
136
VUS
20
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
0
0
0
VUS
0
128
8
0
136
Likely Benign
0
14
1
5
20
Benign
0
1
1
0
2
Total0143195167

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
INTEGRIN, ALPHA-E; ITGAE
MIM #604682 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell transcriptomic analyses reveal distinct immune cell contributions to epithelial barrier dysfunction in checkpoint inhibitor colitis.
Thomas MF et al.·Nat Med
2024
Multiomics-based molecular subtyping based on the commensal microbiome predicts molecular characteristics and the therapeutic response in breast cancer.
Qin W et al.·Mol Cancer
2024
CD8(+) tissue-resident memory T cells are expanded in primary Sjögren's disease and can be therapeutically targeted by CD103 blockade.
Mauro D et al.·Ann Rheum Dis
2024
Integrating Single-Cell RNA-Seq and Bulk RNA-Seq to Construct a Novel γδT Cell-Related Prognostic Signature for Human Papillomavirus-Infected Cervical Cancer.
Wang X et al.·Cancer Control
2024
Identification and characterization of tissue resident memory T cells in malignant pleural effusions associated with non-small cell lung cancer.
Tilsed CM et al.·Immunohorizons
2025
Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes.
Xu W et al.·ESMO Open
2025
Integrin genes and susceptibility to human melanoma.
Lenci RE et al.·Mutagenesis
2012
Phenotypic Characterization and Prognostic Impact of CD103+ Tissue-Resident Memory T Cells in Diffuse Large B-cell Lymphoma.
Savage G et al.·Cancer Immunol Res
2026
Establishment and validation of a novel integrin-based prognostic gene signature that sub-classifies gliomas and effectively predicts immunosuppressive microenvironment.
Qi C et al.·Cell Cycle
2023
Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade.
Banchereau R et al.·J Immunother Cancer
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools