Polyglandular autoimmune syndrome, type 1: genes and variants
Polyglandular autoimmune syndrome, type 1 is linked to 1 analyzed protein (AIRE). 37 DNA variants are known to cause it; 314 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Polyglandular autoimmune syndrome, type 1
AIRE: Autoimmune regulator
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.
37 disease-causing and 314 uncertain variants in AIRE are linked to Polyglandular autoimmune syndrome, type 1.
Where Polyglandular autoimmune syndrome, type 1 variants cluster
- AIRE HSR (positions 1–105): 32 of 37 disease-causing changes, 4.5× more than its size predicts.
Known disease-causing variants in Polyglandular autoimmune syndrome, type 1
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| AIRE R15L | 15 | HSR | Disease-causing (★★) |
| AIRE R15H | 15 | HSR | Disease-causing (★★) |
| AIRE T16M | 16 | HSR | Disease-causing (★★) |
| AIRE T16R | 16 | HSR | Disease-causing (★★) |
| AIRE M1L | 1 | HSR | Disease-causing (★★) |
| AIRE M1V | 1 | HSR | Disease-causing (★★) |
| AIRE A58G | 58 | HSR | Disease-causing (★★) |
| AIRE K83E | 83 | HSR | Disease-causing (★★) |
| AIRE Y85C | 85 | HSR | Disease-causing (★★) |
| AIRE R92W | 92 | HSR | Disease-causing (★★) |
| AIRE W78R | 78 | HSR | Disease-causing (★★) |
| AIRE L87P | 87 | HSR | Disease-causing (★★) |
| AIRE L93R | 93 | HSR | Disease-causing (★★) |
| AIRE A21V | 21 | HSR | Disease-causing (★★) |
| AIRE L28P | 28 | HSR | Disease-causing (★★) |
| AIRE P539L | 539 | Disease-causing (★★) | |
| AIRE G155S | 155 | Disease-causing (★★) | |
| AIRE P326L | 326 | PHD-type 1 | Disease-causing (★★) |
| AIRE R15C | 15 | HSR | Disease-causing (★) |
| AIRE R15G | 15 | HSR | Disease-causing (★) |
| AIRE T16A | 16 | HSR | Disease-causing (★) |
| AIRE Y90C | 90 | HSR | Disease-causing (★) |
| AIRE Y90H | 90 | HSR | Disease-causing (★) |
| AIRE M1K | 1 | HSR | Disease-causing (★) |
| AIRE M1R | 1 | HSR | Disease-causing (★) |
| AIRE M1T | 1 | HSR | Disease-causing (★) |
| AIRE A58D | 58 | HSR | Disease-causing (★) |
| AIRE L81P | 81 | HSR | Disease-causing (★) |
| AIRE R92Q | 92 | HSR | Disease-causing (★) |
| AIRE I18M | 18 | HSR | Disease-causing (★) |
| AIRE L29P | 29 | HSR | Disease-causing (★) |
| AIRE R8H | 8 | HSR | Disease-causing (★) |
| AIRE Q44P | 44 | HSR | Disease-causing (★) |
| AIRE L97P | 97 | HSR | Disease-causing (★) |
| AIRE V80G | 80 | HSR | Disease-causing |
| AIRE C311Y | 311 | PHD-type 1 | Disease-causing |
| AIRE C302Y | 302 | PHD-type 1 | Disease-causing |
Uncertain variants in Polyglandular autoimmune syndrome, type 1 that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| AIRE L93Q | 93 | HSR | Conflicting reports (★) | +7: 5 other pathogenic changes within 3 positions; L93R at the same position is pathogenic; seen in 6.9e-07 of gnomAD DNA copies; REVEL 0.864 |
Which prediction tools work for Polyglandular autoimmune syndrome, type 1
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 100 out of 100
- CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 93 out of 100
- SIFT: 93 out of 100
- PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Diseases related to Polyglandular autoimmune syndrome, type 1
- Inherited Immunodeficiency Diseases, also linked to AIRE
Frequently asked questions
Which genes are linked to Polyglandular autoimmune syndrome, type 1?
In CATVariant, Polyglandular autoimmune syndrome, type 1 is linked to 1 analyzed protein: AIRE (Autoimmune regulator).
How many genetic variants are linked to Polyglandular autoimmune syndrome, type 1?
363 variants: 37 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 314 are of uncertain significance or have conflicting reports.
Which uncertain variants in Polyglandular autoimmune syndrome, type 1 look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example AIRE L93Q. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Polyglandular autoimmune syndrome, type 1?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 24 disease-causing and 12 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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