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

    Gene ID: 773, updated on 2-Nov-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
    mouse all
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    Genomic context

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    See CACNA1A in Genome Data Viewer
    Location:
    19p13.13
    Exon count:
    49
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (13206442..13506479, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (13331719..13631840, complement)
    RS_2024_09 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 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. Benign paroxysmal tonic upgaze, benign paroxysmal torticollis, episodic ataxia and CACNA1A mutation in a family. Roubertie A, et al. J Neurol, 2008 Oct. PMID 18758887
    2. Large scale calcium channel gene rearrangements in episodic ataxia and hemiplegic migraine: implications for diagnostic testing. Labrum RW, et al. J Med Genet, 2009 Nov. PMID 19586927
    3. CACNA1A gene non-synonymous single nucleotide polymorphisms and common migraine in Italy: a case-control association study with a micro-array technology. Gerola S, et al. Clin Chem Lab Med, 2009. PMID 19527141
    4. Early seizures and cerebral oedema after trivial head trauma associated with the CACNA1A S218L mutation. Stam AH, et al. J Neurol Neurosurg Psychiatry, 2009 Oct. PMID 19520699
    5. CACNA1A nonsense mutation is associated with basilar-type migraine and episodic ataxia type 2. Robbins MS, et al. Headache, 2009 Jul. PMID 19486177

    See all (273) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Natural history of non-polyglutamine CACNA1A disease in Austria.
      Title: Natural history of non-polyglutamine CACNA1A disease in Austria.
    2. 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.
    3. CACNA1A-Related Channelopathies: Clinical Manifestations and Treatment Options.
      Title: CACNA1A-Related Channelopathies: Clinical Manifestations and Treatment Options.
    4. 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.
    5. Clinical and genetic characterization of CACNA1A-related disease.
      Title: Clinical and genetic characterization of CACNA1A-related disease.
    6. The complexities of CACNA1A in clinical neurogenetics.
      Title: The complexities of CACNA1A in clinical neurogenetics.
    7. 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.
    8. 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.
    9. 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.
    10. Advances in genotype-phenotype associations for CACNA1A-related epilepsies.
      Title: Advances in genotype-phenotype associations for CACNA1A-related epilepsies.
    Submit: New GeneRIF Correction See all GeneRIFs (206)

    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
    Developmental and epileptic encephalopathy, 42
    MedGen: C4310716 OMIM: 617106 GeneReviews: Not available
    		not available
    Episodic ataxia type 2
    MedGen: C1720416 OMIM: 108500 GeneReviews: Hereditary Ataxia Overview
    		not available
    Migraine, familial hemiplegic, 1
    MedGen: C1832884 OMIM: 141500 GeneReviews: Familial Hemiplegic Migraine
    		not available
    Spinocerebellar ataxia type 6
    MedGen: C0752124 OMIM: 183086 GeneReviews: Hereditary Ataxia Overview, Spinocerebellar Ataxia Type 6
    		not available

    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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    NEW Try the new Transcript table

    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_2024_08

    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

    Gene LinkOut

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

    Chemical Information
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