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    CACNA1S calcium voltage-gated channel subunit alpha1 S [ Homo sapiens (human) ]

    Gene ID: 779, updated on 3-Apr-2024

    Summary

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    Official Symbol
    CACNA1Sprovided by HGNC
    Official Full Name
    calcium voltage-gated channel subunit alpha1 Sprovided by HGNC
    Primary source
    HGNC:HGNC:1397
    See related
    Ensembl:ENSG00000081248 MIM:114208; AllianceGenome:HGNC:1397
    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
    MHS5; DHPRM; HOKPP; TTPP1; CMYP18; Cav1.1; HOKPP1; hypoPP; CCHL1A3; CACNL1A3
    Summary
    This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in esophagus (RPKM 1.7), prostate (RPKM 1.6) and 4 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CACNA1S in Genome Data Viewer
    Location:
    1q32.1
    Exon count:
    44
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (201039512..201112426, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (200296459..200369410, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (201008640..201081554, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2304 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr1:200945792-200946991 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2305 Neighboring gene kinesin family member 21B Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:200969230-200969730 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:200985675-200986222 Neighboring gene Sharpr-MPRA regulatory region 10908 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2306 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2307 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1683 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:200991037-200991644 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1684 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1685 Neighboring gene uncharacterized LOC101929305 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:200993410-200993567 Neighboring gene Sharpr-MPRA regulatory region 14143 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201021057-201021557 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201022145-201023102 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2308 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201028065-201028818 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201031613-201032386 Neighboring gene uncharacterized LOC124904481 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201070239-201070740 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201070741-201071240 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201072987-201073503 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1686 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201084381-201084901 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:201095506-201096496 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:201096497-201097487 Neighboring gene achaete-scute family bHLH transcription factor 5 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:201103675-201103881 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2309 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1687 Neighboring gene transmembrane protein 9 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2310

    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. Short-Communication: Variable Expression of Clinical Symptoms and an Unexpected Finding of Vacuolar Myopathy Related to a Pathogenic Variant in the CACNA1S Gene in a Previous Case Report. Benítez-Alonso EO, et al. Cureus, 2022 Apr. PMID 35509735, Free PMC Article
    2. Malignant Hyperthermia: A Killer If Ignored. Bin X, et al. J Perianesth Nurs, 2022 Aug. PMID 35414440
    3. Analysis of Factors That May Affect the Effectiveness of Ketogenic Diet Treatment in Pediatric and Adolescent Patients. Winczewska-Wiktor A, et al. J Clin Med, 2022 Jan 25. PMID 35160058, Free PMC Article
    4. Novel CACNA1S mutation in hypokalaemic periodic paralysis. Luís T, et al. BMJ Case Rep, 2022 Jan 17. PMID 35039355, Free PMC Article
    5. Vacuolar Myopathy Associated to CACNA1S Mutation as a Rare Cause of Late-Onset Limb-Girdle Myopathy: A Case Report. López-Hernández JC, et al. Cureus, 2021 Oct. PMID 34804722, Free PMC Article

    See all (100) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Biallellic variants in CACNA1S cause fetal akinesia sequence, progressive hydrops and stillbirth.
      Title: Biallellic variants in CACNA1S cause fetal akinesia sequence, progressive hydrops and stillbirth.
    2. CACNA1S Variant Associated With a Myalgic Myopathy Phenotype.
      Title: CACNA1S Variant Associated With a Myalgic Myopathy Phenotype.
    3. Congenital Myopathy as a Phenotypic Expression of CACNA1S Gene Mutation: Case Report and Systematic Review of the Literature.
      Title: Congenital Myopathy as a Phenotypic Expression of CACNA1S Gene Mutation: Case Report and Systematic Review of the Literature.
    4. Mutations associated with hypokalemic periodic paralysis: from hotspot regions to complete analysis of CACNA1S and SCN4A genes.
      Title: Mutations associated with hypokalemic periodic paralysis: from hotspot regions to complete analysis of CACNA1S and SCN4A genes.
    5. MRTF-A regulates Ca(2+) release through CACNA1S.
      Title: MRTF-A regulates Ca(2+) release through CACNA1S.
    6. Gating pore currents occur in CaV1.1 domain III mutants associated with HypoPP.
      Title: Gating pore currents occur in CaV1.1 domain III mutants associated with HypoPP.
    7. Structural determinants of voltage-gating properties in calcium channels.
      Title: Structural determinants of voltage-gating properties in calcium channels.
    8. Mutation spectrum and health status in skeletal muscle channelopathies in Japan.
      Title: Mutation spectrum and health status in skeletal muscle channelopathies in Japan.
    9. Investigating the genetic susceptibility to exertional heat illness.
      Title: Investigating the genetic susceptibility to exertional heat illness.
    10. Morphological Alterations of the Sarcotubular System in Permanent Myopathy of Hereditary Hypokalemic Periodic Paralysis with a Mutation in the CACNA1S Gene.
      Title: Morphological Alterations of the Sarcotubular System in Permanent Myopathy of Hereditary Hypokalemic Periodic Paralysis with a Mutation in the CACNA1S Gene.
    Submit: New GeneRIF Correction See all GeneRIFs (50)

    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

    Professional guidelines

    Description
    Professional guideline
    ACMG 2013

    The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in CACNA1S that are pathogenic or expected to be pathogenic.

    GuidelinePubMed

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2016-01-18)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2016-01-18)

    ClinGen Genome Curation Page

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies four loci associated with eruption of permanent teeth.
    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 calmodulin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables molecular function activator activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables small molecule binding EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables voltage-gated calcium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables voltage-gated calcium channel activity IMP
    Inferred from Mutant Phenotype
    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 NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in calcium ion transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to caffeine ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in endoplasmic reticulum organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in extraocular skeletal muscle development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in muscle contraction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in myoblast fusion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuromuscular junction development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of muscle contraction NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in release of sequestered calcium ion into cytosol IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in skeletal muscle adaptation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in skeletal muscle fiber development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in skeletal system development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in striated muscle contraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in I band IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of L-type voltage-gated calcium channel complex ISO
    Inferred from Sequence Orthology
    more info
    		  
    part_of L-type voltage-gated calcium channel complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in T-tubule IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in T-tubule IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in sarcoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 L-type calcium channel subunit alpha-1S
    Names
    calcium channel, voltage-dependent, L type, alpha 1S subunit
    dihydropyridine receptor alpha 1 subunit
    dihydropyridine-sensitive L-type calcium channel alpha-1 subunit
    voltage-gated calcium channel subunit alpha Cav1.1

    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_009816.2 RefSeqGene

      Range
      5141..78055
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000069.3 → NP_000060.2  voltage-dependent L-type calcium channel subunit alpha-1S

      See identical proteins and their annotated locations for NP_000060.2

      Status: REVIEWED

      Source sequence(s)
      AL139159, AL358473
      Consensus CDS
      CCDS1407.1
      UniProtKB/Swiss-Prot
      A4IF51, B1ALM2, Q12896, Q13698, Q13934
      UniProtKB/TrEMBL
      A0A7P0T8M7
      Related
      ENSP00000355192.3, ENST00000362061.4
      Conserved Domains (5) summary
      pfam00520
      Location:1135 → 1392
      Ion_trans; Ion transport protein
      pfam05104
      Location:671 → 777
      Rib_recp_KP_reg; Ribosome receptor lysine/proline rich region
      pfam08763
      Location:1465 → 1536
      Ca_chan_IQ; Voltage gated calcium channel IQ domain
      pfam16885
      Location:1692 → 1833
      CAC1F_C; Voltage-gated calcium channel subunit alpha, C-term
      pfam16905
      Location:1400 → 1463
      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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      201039512..201112426 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005245478.4 → XP_005245535.1  voltage-dependent L-type calcium channel subunit alpha-1S isoform X1

      UniProtKB/TrEMBL
      A0A7P0T8M7, B1ALM3
      Related
      ENSP00000356307.3, ENST00000367338.7
      Conserved Domains (5) summary
      pfam00520
      Location:1135 → 1373
      Ion_trans; Ion transport protein
      pfam05104
      Location:671 → 777
      Rib_recp_KP_reg; Ribosome receptor lysine/proline rich region
      pfam08763
      Location:1446 → 1517
      Ca_chan_IQ; Voltage gated calcium channel IQ domain
      pfam16885
      Location:1673 → 1814
      CAC1F_C; Voltage-gated calcium channel subunit alpha, C-term
      pfam16905
      Location:1381 → 1444
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      200296459..200369410 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054338645.1 → XP_054194620.1  voltage-dependent L-type calcium channel subunit alpha-1S isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13698.4 GenPept UniProtKB/Swiss-Prot:Q13698

    Gene LinkOut

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

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