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

    Gene ID: 93589, updated on 10-Dec-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (1791963..1918652, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (1788097..1914979, complement)
    RS_2024_09 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: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 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
    		not available

    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)

    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_2024_08

    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

      UniProtKB/TrEMBL
      K7EJY1
      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

      UniProtKB/TrEMBL
      K7ER25

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

      UniProtKB/TrEMBL
      K7ER25

    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

      UniProtKB/TrEMBL
      K7EJY1

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

      UniProtKB/TrEMBL
      K7EJY1

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

      UniProtKB/TrEMBL
      K7ER25

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

      UniProtKB/TrEMBL
      K7ER25

    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

      UniProtKB/TrEMBL
      K7EJY1

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

      UniProtKB/TrEMBL
      K7EJY1

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

      UniProtKB/TrEMBL
      K7ER25

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

      UniProtKB/TrEMBL
      K7ER25

    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

    Gene LinkOut

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

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