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    CACNA1E calcium voltage-gated channel subunit alpha1 E [ Homo sapiens (human) ]

    Gene ID: 777, updated on 27-Nov-2024

    Summary

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    Official Symbol
    CACNA1Eprovided by HGNC
    Official Full Name
    calcium voltage-gated channel subunit alpha1 Eprovided by HGNC
    Primary source
    HGNC:HGNC:1392
    See related
    Ensembl:ENSG00000198216 MIM:601013; AllianceGenome:HGNC:1392
    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
    BII; CACH6; DEE69; gm139; Cav2.3; EIEE69; CACNL1A6
    Summary
    Voltage-dependent calcium channels are multisubunit complexes consisting of alpha-1, alpha-2, beta, and delta subunits in a 1:1:1:1 ratio. These 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, gene expression, cell motility, cell division and cell death. This gene encodes the alpha-1E subunit of the R-type calcium channels, which belong to the 'high-voltage activated' group that maybe involved in the modulation of firing patterns of neurons important for information processing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]
    Expression
    Biased expression in brain (RPKM 3.3), adrenal (RPKM 0.4) and 2 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CACNA1E in Genome Data Viewer
    Location:
    1q25.3
    Exon count:
    52
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (181317699..181808084)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (180673125..181163498)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (181452653..181777219)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene MPRA-validated peak492 silencer Neighboring gene long intergenic non-protein coding RNA 1699 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:181277357-181277857 Neighboring gene uncharacterized LOC107985454 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:181287535-181288165 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2185 Neighboring gene uncharacterized LOC107985232 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2186 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2187 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2188 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1611 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:181452360-181452884 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1613 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2189 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:181450844-181451376 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1612 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:181452885-181453408 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2190 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2191 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2192 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2193 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1614 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2194 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:181598156-181598432 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:181737037-181738236 Neighboring gene RNA, 5S ribosomal pseudogene 70 Neighboring gene Sharpr-MPRA regulatory region 5358 Neighboring gene RN7SK pseudogene 229 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:181889418-181889626 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:181960367-181960534 Neighboring gene uncharacterized LOC105371640

    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. A specific tryptophan in the I-II linker is a key determinant of beta-subunit binding and modulation in Ca(V)2.3 calcium channels. Berrou L, et al. Biophys J, 2002 Sep. PMID 12202369, Free PMC Article
    2. CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3. Trombetta M, et al. PLoS One, 2012. PMID 22427875, Free PMC Article
    3. Histidine residues in the IS3-IS4 loop are critical for nickel-sensitive inhibition of the Cav2.3 calcium channel. Kang HW, et al. FEBS Lett, 2007 Dec 22. PMID 18037383
    4. Seizure and movement disorder in CACNA1E developmental and epileptic encephalopathy: Two sides of the same coin or same side of two different coins? Di Micco V, et al. Epileptic Disord, 2024 Aug. PMID 38780451
    5. Variants in the Ca V 2.3 (alpha 1E) subunit of voltage-activated Ca2+ channels are associated with insulin resistance and type 2 diabetes in Pima Indians. Muller YL, et al. Diabetes, 2007 Dec. PMID 17720895

    See all (63) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Seizure and movement disorder in CACNA1E developmental and epileptic encephalopathy: Two sides of the same coin or same side of two different coins?
      Title: Seizure and movement disorder in CACNA1E developmental and epileptic encephalopathy: Two sides of the same coin or same side of two different coins?
    2. Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium channel Cav2.3, altering inactivation kinetics and neuronal excitability.
      Title: Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium channel Cav2.3, altering inactivation kinetics and neuronal excitability.
    3. De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures.
      Title: De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures.
    4. Mutations and clinical significance of calcium voltage-gated channel subunit alpha 1E (CACNA1E) in non-small cell lung cancer.
      Title: Mutations and clinical significance of calcium voltage-gated channel subunit alpha 1E (CACNA1E) in non-small cell lung cancer.
    5. Direct inhibition of CaV2.3 by Gem is dynamin dependent and does not require a direct alfa/beta interaction.
      Title: Direct inhibition of Ca(V)2.3 by Gem is dynamin dependent and does not require a direct alfa/beta interaction.
    6. Cav2.3 R-type calcium channels: from its discovery to pathogenic de novo CACNA1E variants: a historical perspective.
      Title: Cav2.3 R-type calcium channels: from its discovery to pathogenic de novo CACNA1E variants: a historical perspective.
    7. F0F1 ATP synthase regulates extracellular calcium influx in human neutrophils by interacting with Cav2.3 and modulates neutrophil accumulation in the lipopolysaccharide-challenged lung.
      Title: F0F1 ATP synthase regulates extracellular calcium influx in human neutrophils by interacting with Ca(v)2.3 and modulates neutrophil accumulation in the lipopolysaccharide-challenged lung.
    8. The variants in CACNA1E as a cause of DEEs.
      Title: De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias.
    9. This study identified a polymorphism in exon 20 of the CACNA1E gene (Asp859Glu - rs35737760) that is more prevalent in hemiplegic and brain stem aura migraine.
      Title: Possible Involvement of the CACNA1E Gene in Migraine: A Search for Single Nucleotide Polymorphism in Different Clinical Phenotypes.
    10. Carriers of the minor G allele of the rs3845446 SNP exhibited enhanced pain-related phenotypes after gastrointestinal surgery. The pain-related phenotypes of carriers of the minor allele of this SNP after gastrointestinal surgery were opposite to such phenotypes after orthognathic surgery.
      Title: Opposite Associations Between the rs3845446 Single-Nucleotide Polymorphism of the CACNA1E Gene and Postoperative Pain-Related Phenotypes in Gastrointestinal Surgery Versus Previously Reported Orthognathic Surgery.
    Submit: New GeneRIF Correction See all GeneRIFs (30)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Developmental and epileptic encephalopathy, 69
    MedGen: C4748988 OMIM: 618285 GeneReviews: Not available
    		Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2024-09-10)

    ClinGen Genome Curation Page
    Haploinsufficency

    Little evidence for dosage pathogenicity (Last evaluated 2024-09-10)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    Genetics of coronary artery calcification among African Americans, a meta-analysis.
    EBI GWAS Catalog
    Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
    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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    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 calcium ion 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 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 
    enables voltage-gated monoatomic cation channel activity IDA
    Inferred from Direct Assay
    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 chemical synaptic transmission IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in neuronal cell body IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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 R-type calcium channel subunit alpha-1E
    Names
    brain calcium channel II
    calcium channel, L type, alpha-1 polypeptide
    calcium channel, R type, alpha-1 polypeptide
    voltage-dependent calcium channel alpha 1E subunit
    voltage-gated calcium channel alpha subunit Cav2.3

    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_050616.2 RefSeqGene

      Range
      170820..495387
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000721.4 → NP_000712.2  voltage-dependent R-type calcium channel subunit alpha-1E isoform 3

      See identical proteins and their annotated locations for NP_000712.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) is missing an in-frame coding exon compared to variant 1. This results in a shorter isoform (3, also known as alpha-1E-3) missing an internal protein segment compared to isoform 1.
      Source sequence(s)
      AB209499, AK309070, AL160059, AL161734, BC037800, BP230397, KF510705, L29385
      Consensus CDS
      CCDS53443.1
      UniProtKB/TrEMBL
      F8W9Z1
      Related
      ENSP00000356542.1, ENST00000367570.6
      Conserved Domains (4) summary
      pfam17069
      Location:1958 → 2089
      RSRP; Arginine/Serine-Rich protein 1
      pfam00520
      Location:1477 → 1734
      Ion_trans; Ion transport protein
      pfam08763
      Location:1807 → 1881
      Ca_chan_IQ; Voltage gated calcium channel IQ domain
      pfam16905
      Location:1735 → 1805
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated

    2. NM_001205293.3 → NP_001192222.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform 1

      See identical proteins and their annotated locations for NP_001192222.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript, and encodes the longest isoform (1, also known as alpha-1E).
      Source sequence(s)
      AL160059, AL161734, BP230397, BP230632, KF510705, L27745
      Consensus CDS
      CCDS55664.1
      UniProtKB/Swiss-Prot
      B1AM12, B1AM13, B1AM14, Q14580, Q14581, Q15878
      UniProtKB/TrEMBL
      F8W9Z1
      Related
      ENSP00000356545.2, ENST00000367573.7
      Conserved Domains (4) summary
      pfam00520
      Location:1477 → 1734
      Ion_trans; Ion transport protein
      pfam08763
      Location:1807 → 1881
      Ca_chan_IQ; Voltage gated calcium channel IQ domain
      pfam16905
      Location:1735 → 1805
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated
      cl28033
      Location:1978 → 2200
      Herpes_ICP4_C; Herpesvirus ICP4-like protein C-terminal region

    3. NM_001205294.2 → NP_001192223.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) is missing two non-consecutive in-frame coding exons compared to variant 1. This results in a shorter isoform (2, also known as alpha-1E-1) missing two internal protein segments compared to isoform 1.
      Source sequence(s)
      AB209499, AK309070, AL160059, AL161734, BC037800, BP230397, KF510705, L29384
      Consensus CDS
      CCDS55665.1
      UniProtKB/TrEMBL
      F8W9Z1
      Related
      ENSP00000481619.1, ENST00000621791.4
      Conserved Domains (4) summary
      pfam17069
      Location:1939 → 2070
      RSRP; Arginine/Serine-Rich protein 1
      pfam00520
      Location:1458 → 1715
      Ion_trans; Ion transport protein
      pfam08763
      Location:1788 → 1862
      Ca_chan_IQ; Voltage gated calcium channel IQ domain
      pfam16905
      Location:1716 → 1786
      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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      181317699..181808084
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017002244.2 → XP_016857733.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X2

      UniProtKB/TrEMBL
      F8W9Z1

    2. XM_017002243.2 → XP_016857732.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X1

      UniProtKB/TrEMBL
      F8W9Z1

    3. XM_017002249.2 → XP_016857738.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X8

      UniProtKB/TrEMBL
      F8W9Z1

    4. XM_017002248.2 → XP_016857737.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X6

      UniProtKB/TrEMBL
      F8W9Z1

    5. XM_017002246.2 → XP_016857735.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X4

      UniProtKB/TrEMBL
      F8W9Z1

    6. XM_017002245.2 → XP_016857734.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X3

      UniProtKB/TrEMBL
      F8W9Z1

    7. XM_017002247.2 → XP_016857736.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X5

      UniProtKB/TrEMBL
      F8W9Z1

    8. XM_017002250.2 → XP_016857739.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X9

      UniProtKB/TrEMBL
      F8W9Z1

    9. XM_047429979.1 → XP_047285935.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X7

    10. XM_047429980.1 → XP_047285936.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X10

    11. XM_017002251.1 → XP_016857740.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X1

      UniProtKB/TrEMBL
      F8W9Z1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      180673125..181163498
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054338635.1 → XP_054194610.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X2

    2. XM_054338634.1 → XP_054194609.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X1

    3. XM_054338639.1 → XP_054194614.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X6

    4. XM_054338637.1 → XP_054194612.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X4

    5. XM_054338636.1 → XP_054194611.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X3

    6. XM_054338638.1 → XP_054194613.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X5

    7. XM_054338640.1 → XP_054194615.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X7

    8. XM_054338644.1 → XP_054194619.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X10

    9. XM_054338641.1 → XP_054194616.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X8

    10. XM_054338642.1 → XP_054194617.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X9

    11. XM_054338643.1 → XP_054194618.1  voltage-dependent R-type calcium channel subunit alpha-1E isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q15878.3 GenPept UniProtKB/Swiss-Prot:Q15878

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