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    ORAI1 ORAI calcium release-activated calcium modulator 1 [ Homo sapiens (human) ]

    Gene ID: 84876, updated on 2-May-2024

    Summary

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    Official Symbol
    ORAI1provided by HGNC
    Official Full Name
    ORAI calcium release-activated calcium modulator 1provided by HGNC
    Primary source
    HGNC:HGNC:25896
    See related
    Ensembl:ENSG00000276045 MIM:610277; AllianceGenome:HGNC:25896
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    IMD9; TAM2; ORAT1; CRACM1; TMEM142A
    Summary
    The protein encoded by this gene is a membrane calcium channel subunit that is activated by the calcium sensor STIM1 when calcium stores are depleted. This type of channel is the primary way for calcium influx into T-cells. Defects in this gene are a cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 1 (IDTICED1). [provided by RefSeq, Sep 2011]
    Annotation information
    Annotation category: suggests misassembly
    Expression
    Ubiquitous expression in skin (RPKM 16.4), duodenum (RPKM 14.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    12q24.31
    Exon count:
    2
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (121626530..121643109)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (121619725..121636322)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (122064455..122079946)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene lysine demethylase 2B Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122018218-122019153 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:122020089-122021024 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122021025-122021958 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122028863-122029678 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122029679-122030494 Neighboring gene KDM2B divergent transcript Neighboring gene RNA, U6 small nuclear 1004, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4980 Neighboring gene Sharpr-MPRA regulatory region 5022 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122062776-122063276 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4981 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7176 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122070465-122071345 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7177 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7178 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122076353-122076870 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122076871-122077388 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122088979-122089480 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122089481-122089980 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122101860-122102399 Neighboring gene uncharacterized LOC105370034 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122109697-122110623 Neighboring gene MORN repeat containing 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122124874-122125860 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7181 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4984 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4985 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4986 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122165743-122166363 Neighboring gene transmembrane protein 120B Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122194907-122195407 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122204395-122204898 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122207988-122208500 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4987 Neighboring gene Sharpr-MPRA regulatory region 8824 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122216872-122217390 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122217391-122217909 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7182 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7183 Neighboring gene ras homolog family member F, filopodia associated

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Orai1 calcium channel inhibition prevents progression of chronic pancreatitis. Szabó V, et al. JCI Insight, 2023 Jul 10. PMID 37227782, Free PMC Article
    2. A pathogenic human Orai1 mutation unmasks STIM1-independent rapid inactivation of Orai1 channels. Yeung PS, et al. Elife, 2023 Feb 20. PMID 36806330, Free PMC Article
    3. Super resolution microscopy analysis reveals increased Orai1 activity in asthma and cystic fibrosis lungs. Goriounova AS, et al. J Cyst Fibros, 2023 Jan. PMID 35961837, Free PMC Article
    4. PKC-Mediated Orai1 Channel Phosphorylation Modulates Ca(2+) Signaling in HeLa Cells. Martínez-Martínez E, et al. Cells, 2022 Jun 27. PMID 35805121, Free PMC Article
    5. ORAI1-Regulated Gene Expression in Breast Cancer Cells: Roles for STIM1 Binding, Calcium Influx and Transcription Factor Translocation. Robitaille M, et al. Int J Mol Sci, 2022 May 24. PMID 35682546, Free PMC Article

    See all (386) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Association of Orai1 and Peizo1 genes expression with cellular proliferation, metastasis and angiogenesis biomarkers in colon tumor biopsies of CRC patients.
      Title: Association of Orai1 and Peizo1 genes expression with cellular proliferation, metastasis and angiogenesis biomarkers in colon tumor biopsies of CRC patients.
    2. Neutrophil-specific ORAI1 Calcium Channel Inhibition Reduces Pancreatitis-associated Acute Lung Injury.
      Title: Neutrophil-specific ORAI1 Calcium Channel Inhibition Reduces Pancreatitis-associated Acute Lung Injury.
    3. Physiological functions of calcium signaling via Orai1 in cancer.
      Title: Physiological functions of calcium signaling via Orai1 in cancer.
    4. Functional differences in agonist-induced plasma membrane expression of Orai1alpha and Orai1beta.
      Title: Functional differences in agonist-induced plasma membrane expression of Orai1α and Orai1β.
    5. Orai1 calcium channel inhibition prevents progression of chronic pancreatitis.
      Title: Orai1 calcium channel inhibition prevents progression of chronic pancreatitis.
    6. Super resolution microscopy analysis reveals increased Orai1 activity in asthma and cystic fibrosis lungs.
      Title: Super resolution microscopy analysis reveals increased Orai1 activity in asthma and cystic fibrosis lungs.
    7. A pathogenic human Orai1 mutation unmasks STIM1-independent rapid inactivation of Orai1 channels.
      Title: A pathogenic human Orai1 mutation unmasks STIM1-independent rapid inactivation of Orai1 channels.
    8. The store-operated Ca[2+] channel Orai1alpha is required for agonist-evoked NF-kappaB activation by a mechanism dependent on PKCbeta2.
      Title: The store-operated Ca(2+) channel Orai1α is required for agonist-evoked NF-κB activation by a mechanism dependent on PKCβ2.
    9. STIM1 and ORAI1 form a novel cold transduction mechanism in sensory and sympathetic neurons.
      Title: STIM1 and ORAI1 form a novel cold transduction mechanism in sensory and sympathetic neurons.
    10. AKAP79 Orchestrates a Cyclic AMP Signalosome Adjacent to Orai1 Ca[2+] Channels.
      Title: AKAP79 Orchestrates a Cyclic AMP Signalosome Adjacent to Orai1 Ca(2+) Channels.
    Submit: New GeneRIF Correction See all GeneRIFs (358)

    Phenotypes

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    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
    Combined immunodeficiency due to ORAI1 deficiency
    MedGen: C2748568 OMIM: 612782 GeneReviews: Not available
    		Compare labs
    Myopathy, tubular aggregate, 2
    MedGen: C4014557 OMIM: 615883 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat modulates ORAI expression in neuron cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ14466

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables calmodulin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables store-operated calcium channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables store-operated calcium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in calcium ion import IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in calcium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in ion channel modulating, G protein-coupled receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in ligand-gated ion channel signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mammary gland epithelium development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in phospholipase C-activating G protein-coupled receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of adenylate cyclase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of calcium ion transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of insulin secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of calcium ion transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in store-operated calcium entry IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in store-operated calcium entry IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in basolateral plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of calcium channel complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in membrane raft IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane raft IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    calcium release-activated calcium channel protein 1
    Names
    calcium release-activated calcium modulator 1
    protein orai-1
    transmembrane protein 142A

    NCBI Reference Sequences (RefSeq)

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    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_007500.1 RefSeqGene

      Range
      4981..20466
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_93

    mRNA and Protein(s)

    1. NM_032790.4 → NP_116179.2  calcium release-activated calcium channel protein 1

      See identical proteins and their annotated locations for NP_116179.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1, coding) represents the protein-coding allele.
      Source sequence(s)
      AC140062, LKPB02000057
      UniProtKB/Swiss-Prot
      Q3MHV3, Q6DHX2, Q96BP7, Q96D31, Q96K71
      Conserved Domains (1) summary
      pfam07856
      Location:73 → 267
      Orai-1; Mediator of CRAC channel activity

    RNA

    1. NR_186857.1 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1, non-coding) represents the non-protein coding allele.
      Source sequence(s)
      AC140062, KF511472
      Related
      ENST00000646827.1

    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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      121626530..121643109
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_018654719.1 Reference GRCh38.p14 PATCHES

      Range
      32306..48880
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      121619725..121636322
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96D31.2 GenPept UniProtKB/Swiss-Prot:Q96D31

    Gene LinkOut

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

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    Chemical Information
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