AIRE (Autoimmune regulator) variants and mutations

AIRE (also known as Autoimmune regulator) is a human protein-coding gene encoding an autoimmune regulator protein. It promotes immune tolerance by driving expression of tissue-restricted antigens in thymic medullary epithelial cells, helping eliminate self-reactive T cells. Biallelic loss-of-function variants cause autoimmune polyendocrine syndrome type 1. This analysis covers 1,149 AIRE variants and mutations. Of these, 83% have computational variant effect predictions. Disease context includes autoimmune polyendocrine syndrome type 1, Autoimmune polyendocrinopathy type 1, and autoimmune polyendocrinopathy. Example AIRE variants include M1K, M1L, and M1R.

Variant analysis overview

Gene: AIRE
Protein: Autoimmune regulator
UniProt accession: O43918
Organism: Homo sapiens
Variants analyzed: 1149
Variant scope: all variants
Completed: 2026-08-19

Variant and mutation evidence

Variant composition: 890 unspecified-consequence records; 2 in-frame insertions; 148 missense variants; 17 frameshift variants; 82 synonymous variants; 5 stop-gained variants; 2 in-frame deletions; 1 splice-region variants; 1 substitution
Prediction scores: 954 variants have prediction scores (83% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: autoimmune polyendocrine syndrome type 1, Autoimmune polyendocrinopathy type 1, autoimmune polyendocrinopathy, rheumatoid arthritis, hereditary disease, neurodegenerative disease, retinal disorder, adrenocortical insufficiency, Genetic chronic primary adrenal insufficiency, primary adrenal insufficiency, familial isolated hypoparathyroidism due to impaired PTH secretion, immunodeficiency disease.

Protein structure and variant hotspots

Protein features: 2 domains.
Structural context: 523 variants have structural context.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable AIRE variants

Examples include M1K, M1L, M1R, M1T, M1V, p.Met1 Ala2insAspTyrLysAspAspAsp, A2S, A2T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

AIRE analysis run — AIRE (1,149 variants) — completed 2026-08-19