AIRE

Chr 21

autoimmune regulator

Also known as: AIRE1, APECED, APS1, APSI, PGA1

NCBI Gene: 326ENSG00000160224UniProt: O43918

This gene encodes a transcriptional regulator that forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. The encoded protein plays an important role in immunity by regulating the expression of autoantigens and negative selection of autoreactive T-cells in the thymus. Mutations in this gene cause the rare autosomal-recessive systemic autoimmune disease termed autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). [provided by RefSeq, Jun 2012]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAutoimmune polyendocrine syndrome 1, with or without reversible metaphyseal dysplasia

Clinical highlights

Gene-disease validity (ClinGen)
autoimmune polyendocrine syndrome type 1 · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
163
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.11
LOEUF
LOF
Mechanism· G2P
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GeneReview available — AIRE
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.11LOEUF
pLI 0.000
Z-score 1.09
OE 0.77 (0.55–1.11)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.00Z-score
OE missense 1.00 (0.92–1.09)
351 obs / 350.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.77 (0.55–1.11)
0≤0.351.4
Missense OE?1.00 (0.92–1.09)
0≤0.61.4
Synonymous OE?1.01
0≤1.21.6
LoF obs/exp: 21 / 27.1Missense obs/exp: 351 / 350.9Syn Z: -0.13

ClinVar Variant Classifications

0 submitted variants in ClinVar

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients