AIRE

Chr 21q22.3

autoimmune regulator

Aliases:: PGA1, APS1
MANE:: ENST00000291582.6

OMIM: 607358 ↗NCBI: 326 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

AIRE · O43918

v62025-08-01

Predicted Aligned Error matrix for AIRE — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

61.2/ 100

Low

545 residues

Confidence breakdown

Very high(≥ 90)22%
Confident(70–90)14%
Low(50–70)14%
Very low(< 50)50%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Autoimmune Polyendocrine Syndrome
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Congenital adrenal hypoplasia
BIALLELIC, autosomal or pseudoautosomal
COVID-19 research
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
DDG2P
BIALLELIC, autosomal or pseudoautosomal
Familial hypoparathyroidism
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Multi-organ autoimmune diabetes
BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders
BIALLELIC, autosomal or pseudoautosomal

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Disease associations (Open Targets)

autoimmune polyendocrine syndrome type 1
0.85
Autoimmune polyendocrinopathy type 1
0.84
autoimmune polyendocrinopathy
0.59
rheumatoid arthritis
0.49
hereditary disease
0.47
neurodegenerative disease
0.43
retinal disorder
0.43
adrenocortical insufficiency
0.42
Genetic chronic primary adrenal insufficiency
0.40
primary adrenal insufficiency
0.37

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Autoimmune regulator

Transcription factor playing an essential role to promote self-tolerance in the thymus by regulating the expression of a wide array of self-antigens that have the commonality of being tissue-restricted in their expression pattern in the periphery, called tissue restricted antigens (TRA) (PubMed:26084028). Binds to G-doublets in an A/T-rich environment; the preferred motif is a tandem repeat of 5'-ATTGGTTA-3' combined with a 5'-TTATTA-3' box. Binds to nucleosomes (By similarity). Binds to chromatin and interacts selectively with histone H3 that is not methylated at 'Lys-4', not phosphorylated at 'Thr-3' and not methylated at 'Arg-2'. Functions as a sensor of histone H3 modifications that are important for the epigenetic regulation of gene expression. Mainly expressed by medullary thymic epithelial cells (mTECs), induces the expression of thousands of tissue-restricted proteins, which are presented on major histocompatibility complex class I (MHC-I) and MHC-II molecules to developing T-cells percolating through the thymic medulla (PubMed:26084028). Also induces self-tolerance through other mechanisms such as the regulation of the mTEC differentiation program. Controls the medullary accumulation of thymic dendritic cells and the development of regulatory T-cell through the regulation of XCL1 expression. Regulates the production of CCR4 and CCR7 ligands in medullary thymic epithelial cells and alters the coordinated maturation and migration of thymocytes. In thimic B-cells, allows the presentation of licensing-dependent endogenous self-anitgen for negative selection. In secondary lymphoid organs, induces functional inactivation of CD4(+) T-cells. Expressed by a distinct bone marrow-derived population, induces self-tolerance through a mechanism that does not require regulatory T-cells and is resitant to innate inflammatory stimuli (By similarity)