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CACNA2D4 calcium voltage-gated channel auxiliary subunit alpha2delta 4 [ Homo sapiens (human) ]

Gene ID: 93589, updated on 3-Apr-2024

Summary

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Official Symbol
CACNA2D4provided by HGNC
Official Full Name
calcium voltage-gated channel auxiliary subunit alpha2delta 4provided by HGNC
Primary source
HGNC:HGNC:20202
See related
Ensembl:ENSG00000151062 MIM:608171; AllianceGenome:HGNC:20202
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
RCD4
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 testis (RPKM 1.1), appendix (RPKM 1.0) and 24 other tissues See more
Orthologs
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Genomic context

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See CACNA2D4 in Genome Data Viewer
Location:
12p13.33
Exon count:
39
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (1791963..1918652, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (1788097..1914979, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (1901129..2027818, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene SDA1 domain containing 1 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4122 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr12:1854087-1854680 Neighboring gene adiponectin receptor 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:1875063-1875563 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr12:1885224-1885742 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr12:1885743-1886260 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:1904713-1905280 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:1905392-1906297 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:1906298-1907202 Neighboring gene uncharacterized LOC105369602 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:1913659-1914581 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5812 Neighboring gene ribosomal protein S4X pseudogene 14 Neighboring gene uncharacterized LOC105369601 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:1929301-1930047 Neighboring gene Sharpr-MPRA regulatory region 2999 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:1937325-1937864 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:1939727-1940340 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:1944610-1945110 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:1953159-1954115 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:1980283-1980782 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:1979781-1980282 Neighboring gene uncharacterized LOC124902858 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:2021735-2022235 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:2025891-2026467 Neighboring gene leucine rich repeats and transmembrane domains 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:2042322-2042920 Neighboring gene lysosomal associated membrane protein 1 pseudogene 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:2063223-2064422 Neighboring gene long intergenic non-protein coding RNA 940 Neighboring gene Sharpr-MPRA regulatory region 10568 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:2112705-2113344 Neighboring gene decapping mRNA 1B Neighboring gene calcium voltage-gated channel subunit alpha1 C

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. Mutations in CACNA2D4 Cause Distinctive Retinal Dysfunction in Humans. Ba-Abbad R, et al. Ophthalmology, 2016 Mar. PMID 26560832
  2. Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders. Van Den Bossche MJ, et al. Am J Med Genet B Neuropsychiatr Genet, 2012 Jun. PMID 22488967
  3. Founder Ashkenazi Jewish mutations of large deletion in the inherited retinal dystrophy genes. Chiang JP, et al. Ophthalmic Genet, 2018 Jan-Feb. PMID 28726569
  4. Mutation in the auxiliary calcium-channel subunit CACNA2D4 causes autosomal recessive cone dystrophy. Wycisk KA, et al. Am J Hum Genet, 2006 Nov. PMID 17033974, Free PMC Article
  5. Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit. Qin N, et al. Mol Pharmacol, 2002 Sep. PMID 12181424

See all (12) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. We find that increasing the expression of Cav at the synaptic membrane is an evolutionarily conserved function of Cacna2d4b. Yet, since both paralogs participate in cone synaptic transmission, we propose partial subfunctionalization in zebrafish. Similar to human patients, our double KO zebrafish model shows mild cone dysfunction, which was not associated with signs of retinal degeneration.
    Title: A New Zebrafish Model for CACNA2D4-Dysfunction.
  2. We have confirmed the TRPM1 36,445 bp deletion is a founder mutation in the Ashkenazi-Jewish (AJ) population with a carrier rate of 1 in 50. We have also confirmed the 35,741 bp deletion in the CACNA2D4 gene is a founder mutation in the AJ population with a carrier rate of 1 in 56.
    Title: Founder Ashkenazi Jewish mutations of large deletion in the inherited retinal dystrophy genes.
  3. This report describes a distinctive ERG phenotype, predominantly involving the cone pathways, in 2 unrelated patients from different ethnic backgrounds with homozygous mutations in CACNA2D4 and normal retinal imaging
    Title: Mutations in CACNA2D4 Cause Distinctive Retinal Dysfunction in Humans.
  4. A rare, partial deletion of 35.7 kb in CACNA2D4 in two unrelated late onset bipolar I patients and in one control individual, were identified.
    Title: Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders.
  5. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
  6. Calcium channel alpha(2)delta-4 subunit has limited distribution in special cell types of the pituitary, adrenal gland, colon, and fetal liver.
    Title: Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit.
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
Retinal cone dystrophy 4
MedGen: C1864849 OMIM: 610478 GeneReviews: Not available
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EBI GWAS Catalog

Description
A genome-wide association study of behavioral disinhibition.
EBI GWAS Catalog
Gene-Smoking Interactions Identify Several Novel Blood Pressure Loci in the Framingham Heart Study.
EBI GWAS Catalog
Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects.
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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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
  
enables voltage-gated calcium channel activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in calcium ion transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in detection of light stimulus involved in visual perception IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
part_of voltage-gated calcium channel complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of voltage-gated calcium channel complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
voltage-dependent calcium channel subunit alpha-2/delta-4
Names
alpha2delta-4
calcium channel, voltage-dependent, alpha 2/delta subunit 4
voltage-gated calcium channel alpha(2)delta-4 subunit
voltage-gated calcium channel subunit alpha-2/delta-4

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_012663.2 RefSeqGene

    Range
    5053..131742
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_172364.5 → NP_758952.4  voltage-dependent calcium channel subunit alpha-2/delta-4

    See identical proteins and their annotated locations for NP_758952.4

    Status: REVIEWED

    Source sequence(s)
    AC005342, AC005343, AF516695, BX537437
    Consensus CDS
    CCDS44785.1
    UniProtKB/Swiss-Prot
    Q7Z3S7, Q7Z3S8, Q86XZ5, Q8IZS9
    UniProtKB/TrEMBL
    K7EJY1
    Related
    ENSP00000372169.4, ENST00000382722.10
    Conserved Domains (3) summary
    cd01463
    Location:277 → 460
    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:487 → 579
    Cache_1; Cache domain
    pfam08399
    Location:148 → 264
    VWA_N; VWA N-terminal

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
    1791963..1918652 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047429897.1 → XP_047285853.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X2

    Related
    ENSP00000465060.1, ENST00000586184.5

  2. XM_011521041.3 → XP_011519343.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X1

    UniProtKB/TrEMBL
    K7EJY1
    Conserved Domains (3) summary
    cd01463
    Location:277 → 463
    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:490 → 582
    Cache_1; Cache domain
    pfam08399
    Location:148 → 264
    VWA_N; VWA N-terminal

  3. XM_047429899.1 → XP_047285855.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X4

  4. XM_047429898.1 → XP_047285854.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X3

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_018654718.1 Reference GRCh38.p14 PATCHES

    Range
    134107..260796 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054332326.1 → XP_054188301.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X2

  2. XM_054332325.1 → XP_054188300.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X1

  3. XM_054332328.1 → XP_054188303.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X4

  4. XM_054332327.1 → XP_054188302.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    1788097..1914979 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054373864.1 → XP_054229839.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X2

  2. XM_054373863.1 → XP_054229838.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X1

  3. XM_054373866.1 → XP_054229841.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X4

  4. XM_054373865.1 → XP_054229840.1  voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001005737.1: Suppressed sequence

    Description
    NM_001005737.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

  2. NM_001005766.1: Suppressed sequence

    Description
    NM_001005766.1: This RefSeq was temporarily suppressed because currently there is not sufficient data to support this transcript.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q7Z3S7.2 GenPept UniProtKB/Swiss-Prot:Q7Z3S7

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