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    CACNA2D3 calcium voltage-gated channel auxiliary subunit alpha2delta 3 [ Homo sapiens (human) ]

    Gene ID: 55799, updated on 5-Mar-2024

    Summary

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    Official Symbol
    CACNA2D3provided by HGNC
    Official Full Name
    calcium voltage-gated channel auxiliary subunit alpha2delta 3provided by HGNC
    Primary source
    HGNC:HGNC:15460
    See related
    Ensembl:ENSG00000157445 MIM:606399; AllianceGenome:HGNC:15460
    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
    HSA272268
    Summary
    This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in brain (RPKM 3.0), adrenal (RPKM 1.8) and 16 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    3p21.1-p14.3
    Exon count:
    38
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (54122552..55074557)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (54156427..55108831)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (54156579..55108584)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377095 Neighboring gene uncharacterized LOC124909381 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:54121379-54121902 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:54121903-54122425 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14470 Neighboring gene calcium binding tyrosine phosphorylation regulated pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 13251 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:54237261-54237762 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:54246728-54247322 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:54250734-54251234 Neighboring gene NANOG hESC enhancer GRCh37_chr3:54262808-54263341 Neighboring gene uncharacterized LOC124909382 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:54319420-54319921 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:54497979-54498480 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:54498481-54498980 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:54520692-54520885 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:54551370-54551870 Neighboring gene uncharacterized LOC107986088 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:54668358-54668860 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:54668861-54669361 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:54673489-54674415 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr3:54743647-54744366 Neighboring gene ribosomal protein S15 pseudogene 5 Neighboring gene embryonic stem cell related Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:54855004-54855707 Neighboring gene NANOG hESC enhancer GRCh37_chr3:54877384-54877885 Neighboring gene CACNA2D3 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:54973116-54973616 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:54986884-54987876 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:54987877-54988869 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:54989863-54990854 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:54992683-54993184 Neighboring gene VISTA enhancer hs1436 Neighboring gene leucine rich repeats and transmembrane domains 1 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr3:55096424-55097039 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:55113410-55113654 Neighboring gene uncharacterized LOC124906243 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:55183044-55183208 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:55194201-55195400 Neighboring gene long intergenic non-protein coding RNA 2017 Neighboring gene long intergenic non-protein coding RNA 2030

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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

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    Related articles in PubMed

    1. A two-stage genome-wide association study identifies novel germline genetic variations in CACNA2D3 associated with radiotherapy response in nasopharyngeal carcinoma. Yu LL, et al. J Transl Med, 2023 Jan 9. PMID 36624463, Free PMC Article
    2. Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer. Kong X, et al. Oncol Rep, 2020 Jan. PMID 31746409, Free PMC Article
    3. Genes, biomarkers, and clinical features associated with the course of bipolar disorder. Smedler E, et al. Eur Neuropsychopharmacol, 2019 Oct. PMID 31378653
    4. CACNA2D3 is downregulated in gliomas and functions as a tumor suppressor. Jin Y, et al. Mol Carcinog, 2017 Mar. PMID 27583705
    5. Genetic contribution to iron status: SNPs related to iron deficiency anaemia and fine mapping of CACNA2D3 calcium channel subunit. Baeza-Richer C, et al. Blood Cells Mol Dis, 2015 Dec. PMID 26460247

    See all (32) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Remote ischemic preconditioning reduces mitochondrial apoptosis mediated by calpain 1 activation in myocardial ischemia-reperfusion injury through calcium channel subunit Cacna2d3.
      Title: Remote ischemic preconditioning reduces mitochondrial apoptosis mediated by calpain 1 activation in myocardial ischemia-reperfusion injury through calcium channel subunit Cacna2d3.
    2. A two-stage genome-wide association study identifies novel germline genetic variations in CACNA2D3 associated with radiotherapy response in nasopharyngeal carcinoma.
      Title: A two-stage genome-wide association study identifies novel germline genetic variations in CACNA2D3 associated with radiotherapy response in nasopharyngeal carcinoma.
    3. CNS sensitisation was associated with a common genetic variant near the calcium channel gene CACNA2D3 at genome-wide significance.
      Title: Genes, biomarkers, and clinical features associated with the course of bipolar disorder.
    4. Results found that CACNA2D3 was lowly expressed in endometrial cancer (EC) tissues and cells. Its overexpression significantly blocked the tumor growth in an in vivo xenograft model while in vitro, it inhibited cell proliferation and migration, and promoted apoptosis and calcium influx. These data revealed that CACNA2D3 functions as a tumor suppressor in EC.
      Title: Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer.
    5. The authors show that ventricular alpha2delta3 expression is low in healthy mice and humans, but significantly elevated in ventricular muscles from DM1 patients with conduction defects.
      Title: Straightjacket/α2δ3 deregulation is associated with cardiac conduction defects in myotonic dystrophy type 1.
    6. Nine of the 32 (28.1%) iCCA patients had gene mutations at chromosome 3p, totaling 11 mutations across five genes. Those included five (15.6%) BAP1 mutations, two each (6.3%) of CACNA2D3 and RASSF1 mutations, and one each (3.1%) of ATG7 and PLCD1 mutations. Six (18.8%) cases had concurrent loss of chromosome 3p and gene mutations.
      Title: Mutations of candidate tumor suppressor genes at chromosome 3p in intrahepatic cholangiocarcinoma.
    7. Findings demonstrate the tumor suppressive role of CACNA2D3 in gliomas. CACNA2D3 operates via Ca 2thorn signaling and the activation of non-canonical Wnt signaling to inhibit cell proliferation and motility and induce apoptosis.
      Title: CACNA2D3 is downregulated in gliomas and functions as a tumor suppressor.
    8. The risk of developing anaemia is increased in reproductive age women carriers of A allele of rs1868505 (CACNA2D3) and/or T allele of rs13194491 (HIST1H2BJ).
      Title: Genetic contribution to iron status: SNPs related to iron deficiency anaemia and fine mapping of CACNA2D3 calcium channel subunit.
    9. CACNA2D3-mediated increase in intracellular calcium (Ca2+) can induce mitochondrial-mediated apoptosis.
      Title: Characterization of CACNA2D3 as a putative tumor suppressor gene in the development and progression of nasopharyngeal carcinoma.
    10. CACNA2D3 is a novel tumor suppressor gene responsible for the 3p21 deletion event that plays a critical suppressing role in the development and progression of esophageal squamous cell carcinoma.
      Title: Investigation of tumor suppressing function of CACNA2D3 in esophageal squamous cell carcinoma.
    Submit: New GeneRIF Correction See all GeneRIFs (20)

    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

    EBI GWAS Catalog

    Description
    A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder.
    EBI GWAS Catalog
    Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.
    EBI GWAS Catalog
    Genetics of coronary artery calcification among African Americans, a meta-analysis.
    EBI GWAS Catalog
    Genome-wide association study in musician's dystonia: a risk variant at the arylsulfatase G locus?
    EBI GWAS Catalog
    Genome-wide association study of antibody response to smallpox vaccine.
    EBI GWAS Catalog
    Genome-wide association study of endometrial cancer in E2C2.
    EBI GWAS Catalog

    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

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables voltage-gated calcium channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in calcium ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of voltage-gated calcium channel complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    voltage-dependent calcium channel subunit alpha-2/delta-3
    Names
    alpha2delta-3
    calcium channel alpha2-delta3 subunit
    calcium channel, voltage-dependent, alpha 2/delta 3 subunit
    calcium channel, voltage-dependent, alpha 2/delta subunit 3
    voltage-gated calcium channel subunit alpha-2/delta-3

    NCBI Reference Sequences (RefSeq)

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    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.

    mRNA and Protein(s)

    1. NM_018398.3 → NP_060868.2  voltage-dependent calcium channel subunit alpha-2/delta-3 precursor

      See identical proteins and their annotated locations for NP_060868.2

      Status: REVIEWED

      Source sequence(s)
      AC092057, AC092797, AC104298, AC109584, AC115282, AC133010, AC137673, AC138059
      Consensus CDS
      CCDS54598.1
      UniProtKB/Swiss-Prot
      B2RPL6, Q8IZS8, Q9NY16, Q9NY18
      Related
      ENSP00000419101.1, ENST00000474759.6
      Conserved Domains (5) summary
      cd01463
      Location:242 → 425
      vWA_VGCC_like; VWA Voltage gated Calcium channel like: Voltage-gated calcium channels are a complex of five proteins: alpha 1, beta 1, gamma, alpha 2 and delta. The alpha 2 and delta subunits result from proteolytic processing of a single gene product and carries at ...
      cd12912
      Location:508 → 622
      PDC2_MCP_like; second PDC (PhoQ/DcuS/CitA) domain of methyl-accepting chemotaxis proteins and similar domains
      pfam08399
      Location:113 → 229
      VWA_N; VWA N-terminal
      pfam08473
      Location:655 → 1068
      VGCC_alpha2; Neuronal voltage-dependent calcium channel alpha 2acd
      pfam02743
      Location:442 → 552
      dCache_1; Cache 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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      54122552..55074557
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      54156427..55108831
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8IZS8.1 GenPept UniProtKB/Swiss-Prot:Q8IZS8

    Gene LinkOut

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

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