U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination
    • Showing Current items.

    AIRE autoimmune regulator [ Homo sapiens (human) ]

    Gene ID: 326, updated on 7-Apr-2024

    Summary

    Go to the top of the page Help
    Official Symbol
    AIREprovided by HGNC
    Official Full Name
    autoimmune regulatorprovided by HGNC
    Primary source
    HGNC:HGNC:360
    See related
    Ensembl:ENSG00000160224 MIM:607358; AllianceGenome:HGNC:360
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    APS1; APSI; PGA1; AIRE1; APECED
    Summary
    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]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    Location:
    21q22.3
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 21 NC_000021.9 (44285876..44298648)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 21 NC_060945.1 (42639932..42652704)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 21 NC_000021.8 (45705759..45718531)

    Chromosome 21 - NC_000021.9Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45642723-45643224 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45643225-45643724 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45645682-45646182 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45646183-45646683 Neighboring gene inducible T cell costimulator ligand Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45659303-45660081 Neighboring gene CRISPRi-FlowFISH-validated ICOSLG and IFNGR2 regulatory element GRCh37_chr21:45660637-45661636 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45662586-45663124 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45667417-45668358 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45669258-45669773 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45669774-45670290 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45670291-45670805 Neighboring gene DNMT3L antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45676001-45676989 Neighboring gene DNA methyltransferase 3 like Neighboring gene H3K27ac hESC enhancer GRCh37_chr21:45677884-45678384 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45681495-45682054 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45685919-45686548 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45686549-45687178 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45691192-45691798 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18564 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr21:45702827-45703430 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45703431-45704032 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45704033-45704636 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45704637-45705238 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13378 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18565 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18566 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18567 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13379 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13380 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18568 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45724667-45725466 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45725506-45726160 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45726161-45726814 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45727470-45728123 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13381 Neighboring gene phosphofructokinase, liver type Neighboring gene Sharpr-MPRA regulatory region 3786 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18569 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45751251-45751752 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45751753-45752252 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13382 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13383 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18570 Neighboring gene cilia and flagella associated protein 410

    Genomic regions, transcripts, and products

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    Go to the top of the pageHelp

    Related articles in PubMed

    1. AIRE illuminates the feature of medullary thymic epithelial cells in thymic carcinoma. Matsumoto M, et al. Cancer Med, 2023 Apr. PMID 36912123, Free PMC Article
    2. Autoimmune Regulator Gene Polymorphisms and the Risk of Primary Immune Thrombocytopenic Purpura: A Case-Control Study. Abdel Ghafar MT, et al. Int J Mol Sci, 2023 Mar 5. PMID 36902438, Free PMC Article
    3. A non-classical presentation of APECED in a family with heterozygous R203X AIRE gene mutation. Radetti G, et al. J Endocrinol Invest, 2023 Mar. PMID 36251243
    4. Spectrum of germline AIRE mutations causing APS-1 and familial hypoparathyroidism. Cranston T, et al. Eur J Endocrinol, 2022 May 24. PMID 35521792, Free PMC Article
    5. Autoimmune polyendocrine syndrome type 1 (APECED) in the Indian population: case report and review of a series of 45 patients. Fierabracci A, et al. J Endocrinol Invest, 2021 Apr. PMID 32767280

    See all (218) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. AIRE is expressed in breast cancer TANs and TAMs to regulate the extrinsic apoptotic pathway and inflammation.
      Title: AIRE is expressed in breast cancer TANs and TAMs to regulate the extrinsic apoptotic pathway and inflammation.
    2. Analysis of the AIRE Gene Promoter in Patients Affected by Autoimmune Polyendocrine Syndromes.
      Title: Analysis of the AIRE Gene Promoter in Patients Affected by Autoimmune Polyendocrine Syndromes.
    3. Association Between AIRE Polymorphisms rs870881(C>T), rs1003854(T>C) and Rheumatoid Arthritis Risk: A Hungarian Case-control Study.
      Title: Association Between AIRE Polymorphisms rs870881(C>T), rs1003854(T>C) and Rheumatoid Arthritis Risk: A Hungarian Case-control Study.
    4. A novel missense mutation in the AIRE gene underlying autoimmune polyglandular syndrome type 1.
      Title: A novel missense mutation in the AIRE gene underlying autoimmune polyglandular syndrome type 1.
    5. A partial form of AIRE deficiency underlies a mild form of autoimmune polyendocrine syndrome type 1.
      Title: A partial form of AIRE deficiency underlies a mild form of autoimmune polyendocrine syndrome type 1.
    6. AIRE illuminates the feature of medullary thymic epithelial cells in thymic carcinoma.
      Title: AIRE illuminates the feature of medullary thymic epithelial cells in thymic carcinoma.
    7. Autoimmune Regulator Gene Polymorphisms and the Risk of Primary Immune Thrombocytopenic Purpura: A Case-Control Study.
      Title: Autoimmune Regulator Gene Polymorphisms and the Risk of Primary Immune Thrombocytopenic Purpura: A Case-Control Study.
    8. The promoter methylations of the autoimmune regulator (AIRE) gene and matrix metalloproteinase-3 (MMP-3) gene may have a role in gestational diabetes mellitus.
      Title: The promoter methylations of the autoimmune regulator (AIRE) gene and matrix metalloproteinase-3 (MMP-3) gene may have a role in gestational diabetes mellitus.
    9. A non-classical presentation of APECED in a family with heterozygous R203X AIRE gene mutation.
      Title: A non-classical presentation of APECED in a family with heterozygous R203X AIRE gene mutation.
    10. [Effects of FoxN1, p63 and AIRE on the process of age-related thymus involution: An update].
      Title: [Effects of FoxN1, p63 and AIRE on the process of age-related thymus involution: An update].
    Submit: New GeneRIF Correction See all GeneRIFs (182)

    Phenotypes

    Go to the top of the page Help

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Polyglandular autoimmune syndrome, type 1
    MedGen: C0085859 OMIM: 240300 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    The human AIRE gene at chromosome 21q22 is a genetic determinant for the predisposition to rheumatoid arthritis in Japanese population.
    EBI GWAS Catalog

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA polymerase II transcription regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA polymerase II transcription regulatory region sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables chromatin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables chromatin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables histone binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables histone binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables translation regulator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in central tolerance induction to self antigen IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in central tolerance induction to self antigen IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in humoral immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in immune response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in negative thymic T cell selection IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in peripheral T cell tolerance induction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in peripheral T cell tolerance induction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of DNA-templated transcription IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of chemokine production ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of thymocyte migration IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of thymocyte migration ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of translation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in thymus epithelium morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in thymus epithelium morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in female germ cell nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in male germ cell nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nuclear body ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

    Go to the top of the page Help
    Preferred Names
    autoimmune regulator
    Names
    autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_009556.1 RefSeqGene

      Range
      4959..17348
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_18

    mRNA and Protein(s)

    1. NM_000383.4 → NP_000374.1  autoimmune regulator

      See identical proteins and their annotated locations for NP_000374.1

      Status: REVIEWED

      Source sequence(s)
      AB006682, AP001060, BC142608
      Consensus CDS
      CCDS13706.1
      UniProtKB/Swiss-Prot
      B2RP50, O43918, O43922, O43932, O75745
      Related
      ENSP00000291582.5, ENST00000291582.6
      Conserved Domains (5) summary
      cd15539
      Location:298 → 340
      PHD1_AIRE; PHD finger 1 found in autoimmune regulator (AIRE)
      cd15540
      Location:433 → 475
      PHD2_AIRE; PHD finger 2 found in autoimmune regulator (AIRE)
      pfam02479
      Location:332 → 375
      Herpes_IE68; Herpesvirus immediate early protein
      pfam03172
      Location:16 → 102
      Sp100; Sp100 domain
      cl02536
      Location:197 → 250
      SAND; SAND domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000021.9 Reference GRCh38.p14 Primary Assembly

      Range
      44285876..44298648
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060945.1 Alternate T2T-CHM13v2.0

      Range
      42639932..42652704
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_000658.2: Suppressed sequence

      Description
      NM_000658.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

    2. NM_000659.1: Suppressed sequence

      Description
      NM_000659.1: This RefSeq was suppressed because it is a nonsense-mediated decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43918.1 GenPept UniProtKB/Swiss-Prot:O43918

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous