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CACNA1A calcium voltage-gated channel subunit alpha1 A [ Homo sapiens (human) ]

Gene ID: 773, updated on 13-Apr-2024

Summary

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Official Symbol
CACNA1Aprovided by HGNC
Official Full Name
calcium voltage-gated channel subunit alpha1 Aprovided by HGNC
Primary source
HGNC:HGNC:1388
See related
Ensembl:ENSG00000141837 MIM:601011; AllianceGenome:HGNC:1388
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
BI; EA2; FHM; MHP; APCA; HPCA; MHP1; SCA6; DEE42; CAV2.1; EIEE42; CACNL1A4
Summary
Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue. Mutations in this gene are associated with 2 neurologic disorders, familial hemiplegic migraine and episodic ataxia 2. This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. But in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-18 to 21-33 in the coding region is associated with spinocerebellar ataxia 6. [provided by RefSeq, Jul 2016]
Expression
Biased expression in brain (RPKM 5.1), stomach (RPKM 1.8) and 6 other tissues See more
Orthologs
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Genomic context

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Location:
19p13.13
Exon count:
49
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (13206442..13506479, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (13331719..13631840, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (13317256..13617293, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14112 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14113 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10197 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14114 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:13263956-13264839 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14115 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10199 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10200 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14116 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14117 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14118 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14119 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14120 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14121 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10201 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:13276087-13276664 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:13278116-13278743 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:13280436-13280936 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:13280937-13281437 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14122 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14123 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14124 Neighboring gene OCT4 hESC enhancer GRCh37_chr19:13295659-13296160 Neighboring gene Sharpr-MPRA regulatory region 13602 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:13297985-13298895 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:13297074-13297984 Neighboring gene ribosomal protein L12 pseudogene 42 Neighboring gene CRISPRi-FlowFISH-validated PRDX2 regulatory element 7 Neighboring gene MPRA-validated peak3367 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10202 Neighboring gene calcium voltage-gated channel subunit alpha1 A repeat instability region Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14125 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10203 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:13319630-13320530 Neighboring gene immediate early response 2 Neighboring gene MPRA-validated peak3368 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14127 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:13335615-13336116 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:13336117-13336616 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:13337139-13337640 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:13341838-13342338 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:13342339-13342839 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10204 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr19:13371552-13372751 Neighboring gene Sharpr-MPRA regulatory region 13658 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr19:13385818-13387017 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10205 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14132 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr19:13445719-13446918 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr19:13509521-13510720 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:13511134-13511634 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:13511635-13512135 Neighboring gene Sharpr-MPRA regulatory region 1233 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:13618335-13618861 Neighboring gene uncharacterized LOC107985287 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:13700158-13700387 Neighboring gene Sharpr-MPRA regulatory region 13460 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr19:13732208-13732929 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:13776728-13777228 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:13777229-13777729 Neighboring gene uncharacterized LOC105372284 Neighboring gene MPRA-validated peak3373 silencer Neighboring gene MPRA-validated peak3374 silencer

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. Clinical and genetic characterization of CACNA1A-related disease. Lipman AR, et al. Clin Genet, 2022 Oct. PMID 35722745, Free PMC Article
  2. [Diversity of CACNA1A-related disorders]. Rudenskaya GE, et al. Zh Nevrol Psikhiatr Im S S Korsakova, 2021. PMID 35041321
  3. Next-generation sequencing identified a novel CACNA1A I1379F variant in a familial hemiplegic migraine type 1 pedigree: A case report. Luan H, et al. Medicine (Baltimore), 2021 Dec 23. PMID 34941060, Free PMC Article
  4. The complexities of CACNA1A in clinical neurogenetics. Hommersom MP, et al. J Neurol, 2022 Jun. PMID 34806130
  5. Clinical and molecular spectrum of P/Q type calcium channel Cav2.1 in epileptic patients. Alehabib E, et al. Orphanet J Rare Dis, 2021 Nov 2. PMID 34727962, Free PMC Article

See all (268) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Adult-onset Migraine and Very Late Onset Ataxia Due to a Novel Pathogenic Variant of the CACNA1A Gene.
    Title: Adult-onset Migraine and Very Late Onset Ataxia Due to a Novel Pathogenic Variant of the CACNA1A Gene.
  2. CACNA1A-Related Channelopathies: Clinical Manifestations and Treatment Options.
    Title: CACNA1A-Related Channelopathies: Clinical Manifestations and Treatment Options.
  3. High-Throughput Sequencing Data Reveal an Antiangiogenic Role of HNF4A-Mediated CACNA1A/VEGFA Axis in Proliferative Diabetic Retinopathy.
    Title: High-Throughput Sequencing Data Reveal an Antiangiogenic Role of HNF4A-Mediated CACNA1A/VEGFA Axis in Proliferative Diabetic Retinopathy.
  4. Clinical and genetic characterization of CACNA1A-related disease.
    Title: Clinical and genetic characterization of CACNA1A-related disease.
  5. The complexities of CACNA1A in clinical neurogenetics.
    Title: The complexities of CACNA1A in clinical neurogenetics.
  6. Next-generation sequencing identified a novel CACNA1A I1379F variant in a familial hemiplegic migraine type 1 pedigree: A case report.
    Title: Next-generation sequencing identified a novel CACNA1A I1379F variant in a familial hemiplegic migraine type 1 pedigree: A case report.
  7. Biallelic variants in genes previously associated with dominant inheritance: CACNA1A, RET and SLC20A2.
    Title: Biallelic variants in genes previously associated with dominant inheritance: CACNA1A, RET and SLC20A2.
  8. Three Novel Genetic Variants in the FAM110D, CACNA1A, and NLRP12 Genes Are Associated With Susceptibility to Hypertension Among Dai People.
    Title: Three Novel Genetic Variants in the FAM110D, CACNA1A, and NLRP12 Genes Are Associated With Susceptibility to Hypertension Among Dai People.
  9. Advances in genotype-phenotype associations for CACNA1A-related epilepsies.
    Title: Advances in genotype-phenotype associations for CACNA1A-related epilepsies.
  10. [Diversity of CACNA1A-related disorders].", trans "Raznoobrazie boleznei, svyazannykh s genom CACNA1A.
    Title: [Diversity of CACNA1A-related disorders].
Submit: New GeneRIF Correction See all GeneRIFs (205)

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

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2017-05-21)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2017-05-21)

ClinGen Genome Curation PagePubMed

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 amyloid-beta binding IC
Inferred by Curator
more info
 PubMed 
enables high voltage-gated calcium channel activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables high voltage-gated calcium channel activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables high voltage-gated calcium channel activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables syntaxin binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables voltage-gated calcium channel activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables voltage-gated calcium channel activity IGI
Inferred from Genetic Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in calcium ion import across plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in calcium ion transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to amyloid-beta IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to amyloid-beta IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in chemical synaptic transmission IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in modulation of chemical synaptic transmission IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of cytosolic calcium ion concentration IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to amyloid-beta IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in cell projection IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane NAS
Non-traceable Author Statement
more info
 PubMed 
located_in membrane TAS
Traceable Author Statement
more info
 PubMed 
is_active_in neuronal cell body IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in neuronal cell body ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in synapse IEA
Inferred from Electronic Annotation
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 P/Q-type calcium channel subunit alpha-1A
Names
brain calcium channel 1
brain calcium channel I
calcium channel, L type, alpha-1 polypeptide
calcium channel, voltage-dependent, P/Q type, alpha 1A subunit
fetal brain Ca2+ voltage-gated channel alpha1A pore-forming subunit
voltage-gated calcium channel subunit alpha Cav2.1

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_011569.1 RefSeqGene

    Range
    5001..305019
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_7

mRNA and Protein(s)

  1. NM_000068.4 → NP_000059.3  voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform 1

    See identical proteins and their annotated locations for NP_000059.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) uses an alternate splice site in the 3' coding region that results in a frameshift, compared to variant 2. The resulting isoform (1) has a shorter and distinct C-terminus that does not include the polyglutamine tract, compared to isoform 2.
    Source sequence(s)
    AB035726, AC008540, AC011446, AF004883, BQ340521
    Consensus CDS
    CCDS82301.1
    UniProtKB/TrEMBL
    A0A384DVW2
    Related
    ENSP00000490617.1, ENST00000637432.1
    Conserved Domains (3) summary
    pfam00520
    Location:1586 → 1827
    Ion_trans; Ion transport protein
    pfam08763
    Location:1900 → 1974
    Ca_chan_IQ; Voltage gated calcium channel IQ domain
    pfam16905
    Location:1835 → 1898
    GPHH; Voltage-dependent L-type calcium channel, IQ-associated

  2. NM_001127221.2 → NP_001120693.1  voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform 3

    See identical proteins and their annotated locations for NP_001120693.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses two alternate splice sites, lacks two alternate exons, and includes an additional exon, compared to variant 2. The resulting isoform (3) differs at 3 internal regions and has a shorter and distinct C-terminus that does not include the polyglutamine tract, compared to isoform 2.
    Source sequence(s)
    AC008540, AC011446, AC124224, AF004883, X99897
    Consensus CDS
    CCDS45999.1
    UniProtKB/TrEMBL
    A0A1B0GTI4
    Related
    ENSP00000489913.1, ENST00000638009.2
    Conserved Domains (3) summary
    pfam00520
    Location:1583 → 1822
    Ion_trans; Ion transport protein
    pfam08763
    Location:1895 → 1969
    Ca_chan_IQ; Voltage gated calcium channel IQ domain
    pfam16905
    Location:1830 → 1893
    GPHH; Voltage-dependent L-type calcium channel, IQ-associated

  3. NM_001127222.2 → NP_001120694.1  voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses two alternate in-frame splice sites and lacks an alternate in-frame exon, compared to variant 2. The resulting isoform (4) differs at three internal regions, compared to isoform 2, and includes the polyglutamine tract near the C-terminus.
    Source sequence(s)
    AB035727, AC008540, AC011446, AC022436, AC026805, AC124224, AF004883
    Consensus CDS
    CCDS45998.1
    UniProtKB/Swiss-Prot
    J3KP41, O00555, P78510, P78511, Q16290, Q92690, Q99790, Q99791, Q99792, Q99793, Q9NS88, Q9UDC4
    UniProtKB/TrEMBL
    A0A1B0GU81
    Related
    ENSP00000353362.5, ENST00000360228.11
    Conserved Domains (4) summary
    pfam00520
    Location:1564 → 1821
    Ion_trans; Ion transport protein
    pfam08763
    Location:1894 → 1968
    Ca_chan_IQ; Voltage gated calcium channel IQ domain
    pfam16905
    Location:1822 → 1892
    GPHH; Voltage-dependent L-type calcium channel, IQ-associated
    cl28033
    Location:2233 → 2503
    Herpes_ICP4_C; Herpesvirus ICP4-like protein C-terminal region

  4. NM_001174080.2 → NP_001167551.1  voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform 5

    See identical proteins and their annotated locations for NP_001167551.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses two alternate splice sites, compared to variant 2. The resulting isoform (5) lacks an internal 3-aa segment and has a shorter and distinct C-terminus that does not include the polyglutamine tract, compared to isoform 2.
    Source sequence(s)
    AC008540, AC011446, AF004883, FJ040507
    Consensus CDS
    CCDS82302.1
    UniProtKB/TrEMBL
    A0A384DVW2, B5TYJ1
    Related
    ENSP00000490578.1, ENST00000636549.1
    Conserved Domains (3) summary
    pfam00520
    Location:1583 → 1824
    Ion_trans; Ion transport protein
    pfam08763
    Location:1897 → 1971
    Ca_chan_IQ; Voltage gated calcium channel IQ domain
    pfam16905
    Location:1832 → 1895
    GPHH; Voltage-dependent L-type calcium channel, IQ-associated

  5. NM_023035.3 → NP_075461.2  voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform 2

    See identical proteins and their annotated locations for NP_075461.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2). This variant includes a (CAG)n-repeat in the coding region, resulting in a polyglutamine tract near the C-terminus.
    Source sequence(s)
    AB035726, AC008540, AC011446, AF004884, BQ340521
    Consensus CDS
    CCDS82300.1
    UniProtKB/TrEMBL
    A0A087WW63, A0A1B0GU81
    Related
    ENSP00000489829.1, ENST00000638029.1
    Conserved Domains (4) summary
    pfam00520
    Location:1586 → 1827
    Ion_trans; Ion transport protein
    pfam05550
    Location:2352 → 2424
    Peptidase_C53; Pestivirus Npro endopeptidase C53
    pfam08763
    Location:1900 → 1974
    Ca_chan_IQ; Voltage gated calcium channel IQ domain
    pfam16905
    Location:1835 → 1898
    GPHH; Voltage-dependent L-type calcium channel, IQ-associated

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_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    13206442..13506479 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    13331719..13631840 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O00555.3 GenPept UniProtKB/Swiss-Prot:O00555

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