AIRE
Chr 21ADARautoimmune regulator
Also known as: AIRE1, APECED, APS1, APSI, PGA1
The protein encoded by this gene is a transcriptional regulator that promotes immune self-tolerance by controlling the expression of tissue-restricted antigens in the thymus, allowing developing T-cells to recognize and eliminate autoreactive cells. Mutations cause autoimmune polyendocrinopathy syndrome type I (APECED), a rare autosomal recessive disorder characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency, typically presenting in childhood. The gene is extremely intolerant to loss-of-function variants, reflecting its critical role in preventing autoimmunity.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Literature Evidence
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
500 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 | 16 | 1 | 27 | 0 | 44 |
Likely Pathogenic | 16 | 4 | 4 | 0 | 24 |
VUS | 1 | 164 | 26 | 8 | 199 |
Likely Benign | 0 | 1 | 120 | 100 | 221 |
Benign | 0 | 0 | 4 | 0 | 4 |
Conflicting | — | 5 | |||
| Total | 33 | 170 | 181 | 108 | 497 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
AIRE · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Characterization of the Fungal Origins in the Autoimmune Polyendocrinopathy of Type 1 Compared With the Autoimmune Polyendocrinopathies of Type 2
RECRUITINGAnalysis of the Role of AIRE in Autoimmune Neurological Diseases Associated With Autoantibodies
RECRUITINGExternal Resources
Links to major genomics databases and tools