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    CACNA2D2 calcium voltage-gated channel auxiliary subunit alpha2delta 2 [ Homo sapiens (human) ]

    Gene ID: 9254, updated on 3-Apr-2024

    Summary

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    Official Symbol
    CACNA2D2provided by HGNC
    Official Full Name
    calcium voltage-gated channel auxiliary subunit alpha2delta 2provided by HGNC
    Primary source
    HGNC:HGNC:1400
    See related
    Ensembl:ENSG00000007402 MIM:607082; AllianceGenome:HGNC:1400
    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
    CASVDD; CACNA2D
    Summary
    Calcium channels mediate the entry of calcium ions into the cell upon membrane polarization. This gene encodes the alpha-2/delta subunit of the voltage-dependent calcium channel complex. The complex consists of the main channel-forming subunit alpha-1, and auxiliary subunits alpha-2/delta, beta, and gamma. The auxiliary subunits function in the assembly and membrane localization of the complex, and modulate calcium currents and channel activation/inactivation kinetics. The subunit encoded by this gene undergoes post-translational cleavage to yield the extracellular alpha2 peptide and a membrane-anchored delta polypeptide. This subunit is a receptor for the antiepileptic drug, gabapentin. Mutations in this gene are associated with early infantile epileptic encephalopathy. Single nucleotide polymorphisms in this gene are correlated with increased sensitivity to opioid drugs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]
    Expression
    Biased expression in lung (RPKM 29.8), testis (RPKM 5.0) and 4 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    3p21.31
    Exon count:
    40
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (50362613..50504244, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (50392335..50534145, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (50400044..50541675, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19905 Neighboring gene CYB561D2-LOC101928965 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50396255-50397145 Neighboring gene cytochrome b561 family member D2 Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr3:50401999-50402580 and GRCh37_chr3:50402581-50403164 Neighboring gene uncharacterized LOC101928965 Neighboring gene NPR2 like, GATOR1 complex subunit Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50408702-50409233 Neighboring gene transmembrane protein 115 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_70577 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_70587 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50425193-50425797 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50425798-50426402 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50426403-50427007 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50431709-50432264 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50432265-50432820 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50432821-50433375 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50437650-50438150 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50438151-50438651 Neighboring gene MPRA-validated peak4651 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50449343-50449842 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50455687-50456623 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50461353-50461897 Neighboring gene RNA, 5S ribosomal pseudogene 131 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50469412-50469992 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50469993-50470573 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50484381-50484882 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50491070-50491624 Neighboring gene uncharacterized LOC105377082 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50492179-50492733 Neighboring gene uncharacterized LOC124909378 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:50497326-50497515 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50502013-50502514 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50504841-50505342 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50522331-50522892 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50525585-50526085 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50530681-50531336 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50533211-50534158 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50541176-50541684 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50541685-50542193 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50549261-50550206 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50553051-50553689 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50560501-50561010 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50562801-50563438 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50569793-50570542 Neighboring gene uncharacterized LOC105377083 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:50575146-50575387 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50576885-50577561 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50584920-50585829 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50586902-50587840 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14398 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19907 Neighboring gene chromosome 3 open reading frame 18 Neighboring gene HemK methyltransferase family member 1

    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. CACNA2D2 promotes tumorigenesis by stimulating cell proliferation and angiogenesis. Warnier M, et al. Oncogene, 2015 Oct 16. PMID 25619833
    2. A novel null homozygous mutation confirms CACNA2D2 as a gene mutated in epileptic encephalopathy. Pippucci T, et al. PLoS One, 2013. PMID 24358150, Free PMC Article
    3. Early infantile epileptic encephalopathy associated with a high voltage gated calcium channelopathy. Edvardson S, et al. J Med Genet, 2013 Feb. PMID 23339110
    4. Pregabalin is a potent and selective ligand for α(2)δ-1 and α(2)δ-2 calcium channel subunits. Li Z, et al. Eur J Pharmacol, 2011 Sep 30. PMID 21651903
    5. Familial form of typical childhood absence epilepsy in a consanguineous context. Abouda H, et al. Epilepsia, 2010 Sep. PMID 20561025

    See all (34) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. show that the action of alpha2delta2 on tumor development occurs not only through a stimulation of proliferation
      Title: CACNA2D2 promotes tumorigenesis by stimulating cell proliferation and angiogenesis.
    2. The investigation of single nucleotide polymorphisms in three genes that have a functional impact on the opioid response: OPRM1, ABCB1 and the calcium channel complex subunit CACNA2D2, is reported.
      Title: Combined analysis of circulating β-endorphin with gene polymorphisms in OPRM1, CACNAD2 and ABCB1 reveals correlation with pain, opioid sensitivity and opioid-related side effects.
    3. CACNA2D2 deletion/methylation is associated with cervical disease progression.
      Title: Alterations of RASSF1A in premalignant cervical lesions: clinical and prognostic significance.
    4. In mice, targeted disruption of Cacna2d2 led to growth retardation, reduced life span, ataxia, enhanced susceptibility to seizures, and cardiac abnormalities. Cacna2d2 may be involved in hereditary cerebellar ataxias and epileptic disorders in humans.
      Title: Cerebellar ataxia, seizures, premature death, and cardiac abnormalities in mice with targeted disruption of the Cacna2d2 gene.
    5. Although transgenic du(2J)/+ mice have a marked reduction in alpha2delta-2 protein, they show no fall in Purkinje somatic calcium currents or increase in cerebellar tyrosine hydroxylase gene expression.
      Title: The ducky(2J) mutation in Cacna2d2 results in reduced spontaneous Purkinje cell activity and altered gene expression.
    6. role in apoptosis in non-small cell lung cancer cells via association with alterations of the intracellular calcium signaling and disruption of mitochondria membrane integrity
      Title: CACNA2D2-mediated apoptosis in NSCLC cells is associated with alterations of the intracellular calcium signaling and disruption of mitochondria membrane integrity.
    7. single nucleotide polymorphism identified
      Title: Identification of a single nucleotide polymorphism in the human alpha 2 delta 2 calcium channel subunit gene.
    Submit: New GeneRIF Correction

    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
    Cerebellar atrophy with seizures and variable developmental delay
    MedGen: C5193132 OMIM: 618501 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

    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

    • KIAA0558

    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
    		  
    involved_in muscle cell development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuromuscular junction development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in organ growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of organ growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of multicellular organism growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in rhythmic synaptic transmission IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    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-2
    Names
    alpha 2 delta calcium channel subunit
    alpha2delta-2
    calcium channel, voltage-dependent, alpha 2/delta subunit 2
    gene 26
    voltage-gated calcium channel subunit alpha-2/delta-2

    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.

    Genomic

    1. NG_034070.1 RefSeqGene

      Range
      5611..146632
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001005505.3 → NP_001005505.1  voltage-dependent calcium channel subunit alpha-2/delta-2 isoform a precursor

      See identical proteins and their annotated locations for NP_001005505.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) lacks an alternate in-frame exon in the central coding region and uses an alternate in-frame splice site in the 3' coding region compared to variant 3. The encoded isoform (a) is shorter than isoform c.
      Source sequence(s)
      AF040709, AL450422, BF373910, Z84492
      Consensus CDS
      CCDS63647.1
      UniProtKB/TrEMBL
      C9JVC9
      Related
      ENSP00000266039.3, ENST00000266039.7
      Conserved Domains (4) summary
      cd01463
      Location:277 → 456
      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 ...
      pfam02743
      Location:485 → 573
      Cache_1; Cache domain
      pfam08399
      Location:141 → 265
      VWA_N; VWA N-terminal
      pfam08473
      Location:580 → 664
      VGCC_alpha2; Neuronal voltage-dependent calcium channel alpha 2acd

    2. NM_001174051.3 → NP_001167522.1  voltage-dependent calcium channel subunit alpha-2/delta-2 isoform c precursor

      See identical proteins and their annotated locations for NP_001167522.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (c, also known as Alpha2delta-2a).
      Source sequence(s)
      AF040709, AJ251368, AL450422, BF373910, Z84492
      Consensus CDS
      CCDS54588.1
      UniProtKB/Swiss-Prot
      A7MD15, Q9NY47, Q9NY48, Q9UEW0, Q9Y268
      UniProtKB/TrEMBL
      C9JVC9
      Related
      ENSP00000418081.1, ENST00000479441.1
      Conserved Domains (4) summary
      cd01463
      Location:277 → 456
      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 ...
      pfam02743
      Location:485 → 573
      Cache_1; Cache domain
      pfam08399
      Location:141 → 265
      VWA_N; VWA N-terminal
      pfam08473
      Location:580 → 663
      VGCC_alpha2; Neuronal voltage-dependent calcium channel alpha 2acd

    3. NM_001291101.1 → NP_001278030.1  voltage-dependent calcium channel subunit alpha-2/delta-2 isoform d

      See identical proteins and their annotated locations for NP_001278030.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has a different 5' structure, lacks an in-frame exon in the central coding region and uses an alternate in-frame splice site in the 3' coding region, resulting in the use of a downstream start codon compared to variant 3. The encoded isoform (d) has a shorter N-terminus compared to isoform c.
      Source sequence(s)
      AF042793, BF373910, Z84492
      Consensus CDS
      CCDS77748.1
      UniProtKB/TrEMBL
      C9JVC9
      Related
      ENSP00000354228.3, ENST00000360963.7
      Conserved Domains (4) summary
      cd01463
      Location:208 → 387
      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 ...
      pfam02743
      Location:416 → 504
      Cache_1; Cache domain
      pfam08399
      Location:72 → 196
      VWA_N; VWA N-terminal
      pfam08473
      Location:511 → 595
      VGCC_alpha2; Neuronal voltage-dependent calcium channel alpha 2acd

    4. NM_001410768.1 → NP_001397697.1  voltage-dependent calcium channel subunit alpha-2/delta-2 isoform e precursor

      Status: REVIEWED

      Source sequence(s)
      AL450422, Z75742, Z75743, Z84492, Z84494
      Consensus CDS
      CCDS93278.1
      UniProtKB/TrEMBL
      C9JE82
      Related
      ENSP00000404631.1, ENST00000429770.5

    5. NM_006030.4 → NP_006021.2  voltage-dependent calcium channel subunit alpha-2/delta-2 isoform b precursor

      See identical proteins and their annotated locations for NP_006021.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region compared to variant 3. The encoded isoform (b, also known as Alpha2delta-2b) is shorter than isoform c.
      Source sequence(s)
      AF040709, AJ251367, AL450422, BF373910, Z84492
      Consensus CDS
      CCDS33763.1
      UniProtKB/TrEMBL
      C9JVC9
      Related
      ENSP00000390329.2, ENST00000424201.7
      Conserved Domains (4) summary
      cd01463
      Location:277 → 456
      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 ...
      pfam02743
      Location:485 → 573
      Cache_1; Cache domain
      pfam08399
      Location:141 → 265
      VWA_N; VWA N-terminal
      pfam08473
      Location:580 → 664
      VGCC_alpha2; Neuronal voltage-dependent calcium channel alpha 2acd

    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
      50362613..50504244 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011534243.3 → XP_011532545.1  voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1

      UniProtKB/TrEMBL
      C9JVC9
      Related
      ENSP00000407393.2, ENST00000423994.6
      Conserved Domains (4) summary
      cd01463
      Location:277 → 456
      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 ...
      pfam02743
      Location:485 → 573
      Cache_1; Cache domain
      pfam08399
      Location:141 → 265
      VWA_N; VWA N-terminal
      pfam08473
      Location:580 → 663
      VGCC_alpha2; Neuronal voltage-dependent calcium channel alpha 2acd

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      50392335..50534145 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054348438.1 → XP_054204413.1  voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NY47.2 GenPept UniProtKB/Swiss-Prot:Q9NY47

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