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CACNA1C Gene

protein-coding   GIFtS: 68
GCID: GC12P002032

Calcium Channel, Voltage-Dependent, L Type, Alpha 1C Subunit


(Previous symbols: CCHL1A1, CACNL1A1)
  See CACNA1C-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Calcium Channel, Voltage-Dependent, L Type, Alpha 1C Subunit1 2     LQT82
CACNL1A11 2 3 5     Calcium Channel, Cardic Dihydropyridine-Sensitive, Alpha-1 Subunit2
CCHL1A11 2 3 5     DHPR, Alpha-1 Subunit2
Calcium Channel, L Type, Alpha-1 Polypeptide, Isoform 1, Cardiac Muscle2 3     Voltage-Dependent L-Type Ca2+ Channel Alpha 1 Subunit2
CACH22 3     Voltage-Dependent L-Type Calcium Channel Subunit Alpha-1C2
CACN22 3     Voltage-Gated L-Type Calcium Channel Cav1.2 Alpha 1 Subunit, Splice
Variant 10*2
TS2 5     Voltage-Gated Calcium Channel Subunit Alpha Cav1.23
CaV1.22     

External Ids:    HGNC: 13901   Entrez Gene: 7752   Ensembl: ENSG000001510677   OMIM: 1142055   UniProtKB: Q139363   

Export aliases for CACNA1C gene to outside databases

Previous GC identifer: GC12P002096


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CACNA1C Gene:
This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx
of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane
segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of
alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these
proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein
encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many
transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion
channel subunits. (provided by RefSeq, Oct 2012)

GeneCards Summary for CACNA1C Gene:
CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit) is a protein-coding gene. Diseases associated with CACNA1C include brugada syndrome 3, and timothy syndrome. GO annotations related to this gene include alpha-actinin binding and calmodulin binding. An important paralog of this gene is SCN5A.

UniProtKB/Swiss-Prot: CAC1C_HUMAN, Q13936
Function: Voltage-sensitive calcium channels (VSCC) 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. The isoform alpha-1C
gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage
activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by
omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and
omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in
excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity
to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on
the channel function

summary for CACNA1C Gene:
Voltage-gated calcium channels (CaV) are present in the membrane of most excitable cells and mediate calcium
influx in response to depolarisation. They regulate intracellular processes such as contraction, secretion,
neurotransmission and gene expression. Voltage-gated calcium channels are formed from four or five distinct
subunits; the alpha-subunit is the largest subunit and incorporates the voltage sensor, conduction pore and
gating apparatus. Using pharmacological and electrophysiological techniques, at least 6 types of
voltage-gated channels have been identified: L, N, P, Q, R and T, which are grouped into three families.
Cav1.x are high-voltage-activated dihydropyridine-sensitive (L-type), Cav2.x are high-voltage-activated
dihydropyridine-insensitive (N-, P- Q- and R-types) and Cav3.x are low-voltage-activated channels (T-type).

Gene Wiki entry for CACNA1C (Cav1.2) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000012.11  NT_009759.17  NC_018923.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the CACNA1C gene promoter:
         STAT5B   Pax-2   XBP-1   Pax-2a   MEF-2A   FOXO1a   aMEF-2   TGIF   Pax-4a   FOXO1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidCACNA1C promoter sequence
   Search Chromatin IP Primers for CACNA1C

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CACNA1C


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12p13.3   Ensembl cytogenetic band:  12p13.33   HGNC cytogenetic band: 12p13.3

CACNA1C Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CACNA1C gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12P002032:  view genomic region     (about GC identifiers)

Start:
2,079,952 bp from pter      End:
2,807,115 bp from pter
Size:
727,164 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: CAC1C_HUMAN, Q13936 (See protein sequence)
Recommended Name: Voltage-dependent L-type calcium channel subunit alpha-1C  
Size: 2221 amino acids; 248977 Da
Subunit: Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1, alpha-2, beta and
delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore-forming and voltage-sensitive
alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel
activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel
activity. Interacts with CACNA2D4. Interacts (via the N-terminus and the C-terminal C and IQ motifs) with CABP1.
The binding via the C motif is calcium independent whereas the binding via IQ requires the presence of calcium
and is mutually exclusive with calmodulin binding. The binding to the cytoplasmic N-terminal domain is calcium
independent but is essential for the channel modulation. Interacts (via C-terminal CDB motif) with CABP5; in a
calcium-dependent manner (By similarity). Interacts with CIB1; the interaction increases upon cardiomyocytes
hypertrophy (By similarity)
Sequence caution: Sequence=AAA02500.2; Type=Frameshift; Positions=1844;
Selected PDB 3D structures from and Proteopedia for CACNA1C (see all 7):
1T0J (3D)        2BE6 (3D)        2F3Y (3D)        2F3Z (3D)        2LQC (3D)        3G43 (3D)    
Secondary accessions: B2RUT3 E9PDJ0 Q13917 Q13918 Q13919 Q13920 Q13921 Q13922 Q13923 Q13924
Q13925 Q13926 Q13927 Q13928 Q13929 Q13930 Q13932 Q13933 Q14743 Q14744 Q15877 Q4VMI7 Q4VMI8
Q4VMI9 Q6PKM7 Q8N6C0 Q99025 Q99241 Q99875
Alternative splicing: 37 isoforms:  Q13936-1   Q13936-2   Q13936-3   Q13936-4   Q13936-5   Q13936-6   Q13936-7   Q13936-8   
Q13936-9   Q13936-10   Q13936-11   Q13936-12   Q13936-13   Q13936-14   Q13936-15   Q13936-16   
Q13936-17   Q13936-18   Q13936-19   Q13936-20   Q13936-21   Q13936-22   Q13936-23   Q13936-24   
Q13936-25   Q13936-26   Q13936-27   Q13936-28   Q13936-29   Q13936-30   Q13936-31   Q13936-32   
Q13936-33   Q13936-34   Q13936-35   Q13936-36   Q13936-37   (Gene prediction based on EST data)

Explore the universe of human proteins at neXtProt for CACNA1C: NX_Q13936

Explore proteomics data for CACNA1C at MOPED

Post-translational modifications: 

  • Phosphorylation by PKA activates the channel (By similarity)1
  • Glycosylation2 at Asn153, Asn328, Asn1436, Asn1487
  • Modification sites at PhosphoSitePlus

  • See CACNA1C Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (23 alternative transcripts): 
    NP_000710.5  NP_001123299.1  NP_001123301.1  NP_001123302.2  NP_001123303.1  NP_001123304.1  NP_001123305.1  NP_001123306.1  
    NP_001123307.1  NP_001123308.1  NP_001123309.1  NP_001123310.1  NP_001123311.1  NP_001123312.1  NP_001123313.1  NP_001123314.1  
    NP_001123315.1  NP_001123316.1  NP_001123318.1  NP_001161095.1  NP_001161096.2  NP_001161097.1  NP_955630.3  

    ENSEMBL proteins: 
     ENSP00000445849   ENSP00000336982   ENSP00000382563   ENSP00000437936   ENSP00000382504  
     ENSP00000382552   ENSP00000382547   ENSP00000382506   ENSP00000382530   ENSP00000382546  
     ENSP00000382500   ENSP00000382549   ENSP00000266376   ENSP00000382515   ENSP00000382510  
     ENSP00000341092   ENSP00000382537   ENSP00000329877   ENSP00000382557   ENSP00000385724  
     ENSP00000382512   ENSP00000382542   ENSP00000382526   ENSP00000385896  
    Reactome Protein details: Q13936

    CACNA1C Human Recombinant Protein Products:

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    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for CACNA1C 

     
    antibodies-online proteins for CACNA1C (2 products) 

     
    antibodies-online peptides for CACNA1C

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    antibodies-online antibodies for CACNA1C (153 products) 

    CACNA1C Assay Products:

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    antibodies-online kits for CACNA1C (13 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    CACN: Calcium channel subunits
    CACN1: Voltage-gated ion channels / Calcium channels

    IUPHAR Guide to PHARMACOLOGY protein family classification: Cav1.2
    Voltage-gated calcium channels

    Selected InterPro protein domains (see all 6):
     IPR005451 VDCC_L_a1csu
     IPR005446 VDCC_L_a1su
     IPR014873 VDCC_a1su_IQ
     IPR005821 Ion_trans_dom
     IPR027359 Channel_four-helix_dom

    Graphical View of Domain Structure for InterPro Entry Q13936

    ProtoNet protein and cluster: Q13936

    3 Blocks protein domains:
    IPB002077 Calcium channel signature
    IPB005446 L-type voltage-dependent calcium channel alpha-1 subunit signature
    IPB005451 Voltage-dependent L-type calcium channel alpha-1C subunit signature


    UniProtKB/Swiss-Prot: CAC1C_HUMAN, Q13936
    Domain: Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6)
    and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are
    characterized by a series of positively charged amino acids at every third position
    Domain: Binding of intracellular calcium through the EF-hand motif inhibits the opening of the channel (By
    similarity)
    Similarity: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1C subfamily


    Find genes that share domains with CACNA1C           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CAC1C_HUMAN, Q13936
    Function: Voltage-sensitive calcium channels (VSCC) 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. The isoform alpha-1C
    gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage
    activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by
    omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and
    omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in
    excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity
    to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on
    the channel function

         Genatlas biochemistry entry for CACNA1C:
    transverse tubule (TT) calcium voltage-gated channel (VDCC),L type,alpha 1C subunit,dihydropyridine (DHP)
    sensitive,cardiac ,brain,isoform 1

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005216ion channel activity ----
    GO:0005245voltage-gated calcium channel activity IDA12130699
    GO:0005515protein binding IPI11438518
    GO:0005516calmodulin binding IPI15140941
    GO:0008331contributes to high voltage-gated calcium channel activity TAS11576544
         
    Find genes that share ontologies with CACNA1C           About GenesLikeMe


    Phenotypes:
         11 MGI mutant phenotypes (inferred from 13 alleles(MGI details for Cacna1c):
     behavior/neurological  cardiovascular system  embryogenesis  endocrine/exocrine gland  homeostasis/metabolism 
     immune system  integument  mortality/aging  muscle  nervous system 
     reproductive system 

    Find genes that share phenotypes with CACNA1C           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for CACNA1C: Cacna1ctm2Hfm Cacna1ctm1Hfm

       genOway: Develop your customized and physiologically relevant rodent model for CACNA1C

    miRNA
    Products:
        
    miRTarBase miRNAs that target CACNA1C:
    hsa-mir-133a-3p (MIRT001203)

    Block miRNA regulation of human, mouse, rat CACNA1C using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate CACNA1C (see all 127):
    hsa-miR-323-3p hsa-miR-140-5p hsa-miR-100* hsa-miR-3938 hsa-miR-4254 hsa-miR-300 hsa-miR-631 hsa-miR-3653
    Browse SwitchGear 3'UTR luciferase reporter plasmids
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CACNA1C


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CAC1C_HUMAN, Q13936: Membrane; Multi-pass membrane protein. Cell membrane (By similarity). Note=The interaction
    between RRAD and CACNB2 regulates its trafficking to the cell membrane (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    plasma membrane5
    endoplasmic reticulum1

    Gene Ontology (GO): Selected cellular component terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002095caveolar macromolecular signaling complex IEA--
    GO:0005737cytoplasm IDA11206130
    GO:0005886plasma membrane TAS--
    GO:0005891voltage-gated calcium channel complex IDA12130699
    GO:0014069postsynaptic density IDA14140941

    Find genes that share ontologies with CACNA1C           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for CACNA1C About   (see all 51)  
    See pathways by source

    SuperPathContained pathways About
    1Hypertrophic cardiomyopathy (HCM)
    Hypertrophic cardiomyopathy (HCM)0.75
    Arrhythmogenic right ventricular cardiomyopathy (ARVC)0.54
    Dilated cardiomyopathy0.75
    Arrhythmogenic right ventricular cardiomyopathy0.54
    2ADP signalling through P2Y purinoceptor 12
    Inhibition of Insulin Secretion by Adrenaline/Noradrenaline0.64
    Beta-agonist/Beta-blocker Pathway, Pharmacodynamics0.34
    3Alzheimer's disease
    Alzheimers Disease0.44
    Alzheimer's disease0.44
    4Type II diabetes mellitus
    Type II diabetes mellitus0.38
    Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics0.38
    5Development Endothelin 1 EDNRA signaling
    Development Endothelin 1 EDNRA transactivation of EGFR0.41
    GnRH signaling pathway0.38


    Find genes that share SuperPaths with CACNA1C           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for CACNA1C (see all 40)
        Caspase Cascade
    Fc-GammaR Pathway
    Intracellular Calcium Signaling
    PDGF Pathway
    BMP Pathway

    Selected GeneGo (Thomson Reuters) Pathways for CACNA1C (see all 6)
        Development Endothelin-1/EDNRA transactivation of EGFR
    Development Beta-adrenergic receptors signaling via cAMP
    Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis
    Apoptosis and survival Anti-apoptotic action of membrane-bound ESR1
    Transcription CREB pathway

    4 BioSystems Pathways for CACNA1C
        Calcium Regulation in the Cardiac Cell
    Nicotine Activity on Chromaffin Cells
    Arrhythmogenic right ventricular cardiomyopathy
    Alzheimers Disease

    3 Reactome Pathways for CACNA1C
        NCAM1 interactions
    Regulation of insulin secretion
    Adrenaline,noradrenaline inhibits insulin secretion

    Selected PharmGKB Pathways for CACNA1C (see all 8)
        Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics
    Antiarrhythmic Pathway, Pharmacodynamics
    Beta-agonist/Beta-blocker Pathway, Pharmacodynamics
    Celecoxib Pathway, Pharmacodynamics
    Nicotine Pathway (Chromaffin Cell), Pharmacodynamics

    Selected Kegg Pathways  (Kegg details for CACNA1C) (see all 22):
        MAPK signaling pathway
    Calcium signaling pathway
    Cardiac muscle contraction
    Adrenergic signaling in cardiomyocytes
    Vascular smooth muscle contraction

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CACNA1C: 
              Hypertension in human mouse rat
              Neuronal Ion Channels in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for CACNA1C

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for CACNA1C (Q139361, 2, 3 ENSP000002663764) via UniProtKB, MINT, STRING, and/or I2D (see all 88)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CALM3P621581, 2, 3EBI-1038838,EBI-397435 MINT-8087834 MINT-8087891 MINT-8087783 MINT-8087930 MINT-8087912 MINT-8087767 MINT-8087800 MINT-8087819 MINT-8087850 MINT-8087867 I2D: score=6 
    CALM2P621581, 2, 3, ENSP000002722984EBI-1038838,EBI-397435 MINT-8087834 MINT-8087891 MINT-8087783 MINT-8087930 MINT-8087912 MINT-8087767 MINT-8087800 MINT-8087819 MINT-8087850 MINT-8087867 I2D: score=6 STRING: ENSP00000272298
    CALM1P621581, 2, 3, ENSP000003494674EBI-1038838,EBI-397435 MINT-8087834 MINT-8087891 MINT-8087783 MINT-8087930 MINT-8087912 MINT-8087767 MINT-8087800 MINT-8087819 MINT-8087850 MINT-8087867 I2D: score=6 STRING: ENSP00000349467
    CABP1Q9NZU71, 3, ENSP000003173104EBI-1038838,EBI-907894 I2D: score=4 STRING: ENSP00000317310
    IL16Q140053, ENSP000003029354I2D: score=3 STRING: ENSP00000302935
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 25):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006112energy reserve metabolic process TAS--
    GO:0006811ion transport ----
    GO:0006816calcium ion transport ----
    GO:0006874cellular calcium ion homeostasis ----
    GO:0006939smooth muscle contraction ----

    Find genes that share ontologies with CACNA1C           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Compounds for CACNA1C available from Tocris Bioscience    About this table
    CompoundAction CAS #
    omega-Conotoxin GVIACa2+ channel blocker (N-type)[106375-28-4]
    (+-)-Bay K 8644Ca2+-channel activator (L-type)[71145-03-4]
    NNC 55-0396 dihydrochlorideHighly selective Ca2+ channel blocker (T-type)[357400-13-6]
    PregabalinAnticonvulsant. Selectively binds the alpha2delta subunit of voltage-sensitive calcium channels[148553-50-8]
    Mibefradil dihydrochlorideCa2+ channel blocker (T-type)[116644-53-2]

    2 HMDB Compounds for CACNA1C    About this table
    CompoundSynonyms CAS #PubMed Ids
    CalciumCa (see all 2)7440-70-2--
    VerapamilAkilen (see all 107)52-53-9--

    Selected DrugBank Compounds for CACNA1C (see all 18)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    NimodipineNimodipino [INN-Spanish] (see all 2)66085-59-4targetinhibitor8731425 20335610 17705883 11752352 20334460 19844625 20661350
    Mibefradil-- 116644-53-2targetinhibitor10372226 10665814 16899990 16306443
    NisoldipineNisoldipin (see all 3)63675-72-9targetinhibitor9584217 9846638 11752352 7592963
    VerapamilVerapamil [Usan:Ban:Inn] (see all 4)52-53-9targetinhibitor9846638 19125880 15286207 15880143
    FelodipineDl-Felodipine (see all 4)72509-76-3targetinhibitor10525060 11752352 17475903
    IbutilideIbutilida [INN-Spanish] (see all 3)122647-32-9targetactivator15926871 9257085 11752352
    Isradipine(+/-)-Isradipine (see all 5)75695-93-1targetinhibitor12135765 9607315 10766758
    Cinnarizine-- 298-57-7targetinhibitor3530295 1281221
    Drotaverine-- 985-12-6targetinhibitor12823389 12163106
    Magnesium SulfateBitter salt (see all 6)7487-88-9target--17139284 17016423

    Selected IUPHAR Ligands for CACNA1C (Cav1.2) (see all 11)    About this table
    LigandTypeActionAffinityPubmed IDs
    [3H](+)-isradipine
    Gating inhibitorNone10.1 - 1110072735
    nifedipine
    Gating inhibitorAntagonist7 - 817916557
    nisoldipine
    Gating inhibitorNone7.115454078
    Pb2+
    Pore BlockerAntagonist6.412435810
    mibefradil
    Pore BlockerAntagonist4.910991994
    diltiazem
    Channel blockerNone4.9--
    SZ(+)-(S)-202-791
    ActivatorNone4.9--
    calciseptine
    Channel blockerNone4.9--
    FPL64176
    ActivatorNone4.9--
    (-)-(S)-BayK8644
    ActivatorNone4.9--

    2 Novoseek inferred chemical compound relationships for CACNA1C gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    dihydropyridine 69.8 5 20382537 (1), 9436445 (1), 18048029 (1)
    calcium 63.1 52 18718913 (3), 17001293 (3), 17224447 (2), 12645522 (2) (see all 28)

    3 PharmGKB related drug/compound annotations for CACNA1C gene    About this table
    Drug/compound PharmGKB Annotation
    atenololCA  
    calcium channel blockersCA  
    verapamilCA  



    Find genes that share compounds with CACNA1C           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
    About This Section

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    REFSEQ mRNAs for CACNA1C gene (23 alternative transcripts): 
    NM_000719.6  NM_001129827.1  NM_001129829.1  NM_001129830.2  NM_001129831.1  NM_001129832.1  NM_001129833.1  NM_001129834.1  
    NM_001129835.1  NM_001129836.1  NM_001129837.1  NM_001129838.1  NM_001129839.1  NM_001129840.1  NM_001129841.1  NM_001129842.1  
    NM_001129843.1  NM_001129844.1  NM_001129846.1  NM_001167623.1  NM_001167624.2  NM_001167625.1  NM_199460.3  

    Unigene Cluster for CACNA1C:

    Calcium channel, voltage-dependent, L type, alpha 1C subunit
    Hs.118262  [show with all ESTs]
    Unigene Representative Sequence: NM_199460
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 30):
    ENST00000543114 ENST00000335762(uc001qkv.1) ENST00000399655(uc009zdu.1 uc009zdv.1 uc001qkb.2 uc001qkc.2 uc001qjz.2 uc001qkd.2 uc001qke.2 uc001qkf.2 uc009zdw.1 uc001qkg.2 uc001qkh.2 uc001qkl.2 uc001qkj.2 uc001qkk.2 uc001qkn.2 uc001qkm.2 uc001qko.2 uc001qkp.2 uc001qkq.2 uc001qku.2 uc001qkr.2 uc001qks.2 uc001qkt.2 uc001qki.1 uc010sea.1 uc001qky.1)
    ENST00000480911(uc001qka.1) ENST00000399595 ENST00000399644 ENST00000399638
    ENST00000399597 ENST00000399621 ENST00000399637 ENST00000399591 ENST00000399641
    ENST00000347598 ENST00000399606 ENST00000399601 ENST00000344100 ENST00000399629
    ENST00000327702
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate CACNA1C (see all 127):
    hsa-miR-323-3p hsa-miR-140-5p hsa-miR-100* hsa-miR-3938 hsa-miR-4254 hsa-miR-300 hsa-miR-631 hsa-miR-3653
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    Additional mRNA sequence: 

    AB209016.1 AF070589.1 AF465484.1 AJ224873.1 AJ536834.1 AJ537510.1 AK092125.1 AK302698.1 
    AK308652.1 AK309111.1 AY129012.1 AY562395.1 AY562396.1 AY830711.1 AY830712.1 AY830713.1 
    BC093695.1 BC146846.1 L29529.1 L29534.1 L29536.1 M57971.1 M57972.1 Z26294.1 
    Z26295.1 Z34809.1 Z34810.1 Z34811.1 Z34812.1 Z34813.1 Z34814.1 Z34815.1 
    Z34816.1 Z34817.1 Z34818.1 Z34819.1 Z34820.1 Z34821.1 Z34822.1 Z74996.1 

    19 DOTS entries:

    DT.406816  DT.444589  DT.92422512  DT.95374511  DT.92422506  DT.100816328  DT.100816329  DT.100816323 
    DT.40128584  DT.40278694  DT.95258545  DT.95374510  DT.121114526  DT.92422507  DT.430474  DT.91685371 
    DT.95153097  DT.100690452  DT.75144354 

    Selected AceView cDNA sequences (see all 82):

    Z34811 AA136881 AJ224873 Z34810 BQ706122 Z34814 Z34817 AF465484 
    AI016238 NM_000719 Z34816 Z34815 Z34813 CR605077 Z34812 AA126682 
    M57972 AJ537510 Z34821 Z34820 Z34809 Z26295 Z34818 AA173146 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    CACNA1C expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    CACNA1C Expression
    About this image


    CACNA1C expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Heart (Cardiovascular System)    fully expand to see all 3 entries
             Early cardiomyocytes
     
     NULL (Cardiovascular System)    fully expand to see all 2 entries
             Early cardiomyocytes
     
     Amnion (Extraembryonic Tissues)
             Amniotic Epithelial Cells Amniotic Membrane
     
     Ovary (Reproductive System)
             Cumulus Cells Antral Follicle
    CACNA1C Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CACNA1C Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.118262

    UniProtKB/Swiss-Prot: CAC1C_HUMAN, Q13936
    Tissue specificity: Expressed in brain, heart, jejunum, ovary, pancreatic beta-cells and vascular smooth muscle.
    Overall expression is reduced in atherosclerotic vascular smooth muscle

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CACNA1C: 
              Hypertension in human mouse rat
              Neuronal Ion Channels in human mouse rat

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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for CACNA1C gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Cacna1c1 , 5 calcium channel, voltage-dependent, L type, alpha 1C more1, 5 89.61(n)1
    95.1(a)1
      6 (55.86 cM)5
    122881  NM_001255999.11  NP_001242928.11 
     1185923195 
    chicken
    (Gallus gallus)
    Aves CACNA1C1 calcium channel, voltage-dependent, L type, alpha 1C more 83.66(n)
    91.77(a)
      395891  XM_416388.4  XP_416388.4 
    lizard
    (Anolis carolinensis)
    Reptilia CACNA1C6
    calcium channel, voltage-dependent, L type, alpha ...
    84(a)
    1 ↔ 1
    5(13474468-13704933)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia cacna1c1 calcium channel, voltage-dependent, L type, alpha 1C more 78.44(n)
    86.49(a)
      100488055  XM_002938102.2  XP_002938148.2 
    zebrafish
    (Danio rerio)
    Actinopterygii cacna1c2 calcium channel, voltage-dependent, L type, alpha 1C more 78.4(n)   170581  AF305689.1 


    ENSEMBL Gene Tree for CACNA1C (if available)
    TreeFam Gene Tree for CACNA1C (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CACNA1C gene
    SCN5A2  SCN9A2  CACNA1D2  SCN7A2  CACNA1I2  CACNA1F2  CACNA1G2  SCN8A2  
    SCN10A2  SCN3A2  SCN2A2  CACNA1S2  CACNA1H2  SCN11A2  SCN4A2  SCN1A2  
    13 SIMAP similar genes for CACNA1C using alignment to 11 protein entries:     CAC1C_HUMAN (see all proteins):
    CACNA1S    CACNA1D    CACNA1H    CACNA1B    CACNA1F    SCN5A
    SCN3A    CACNA1A    SCN4A    CACNA1E    SCN1A    CACNA1G
    SCN9A

    Find genes that share paralogs with CACNA1C           About GenesLikeMe


    Selected Pseudogenes.org Pseudogenes for CACNA1C (see all 6)
    PGOHUM00000239293 PGOHUM00000239348 PGOHUM00000239385 PGOHUM00000239625 PGOHUM00000239626


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for CACNA1C (see all 12932)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0440394
    Brugada syndrome 3 (BRGDA3)4--see VAR_0440392 A V mis40--------
    VAR_0267424
    Timothy syndrome (TS)4--see VAR_0267422 G R mis40--------
    VAR_0440404
    Brugada syndrome 3 (BRGDA3)4--see VAR_0440402 G R mis40--------
    VAR_0267414
    Timothy syndrome (TS)4--see VAR_0267412 G S mis40--------
    rs1219127761,2
    Cpathogenic12224456(+) GCTGGC/TCCCTG 46 A V mis10--------
    rs803153851,2
    Cpathogenic12614098(+) TTCTCA/GGTGTG 42 S G int1 mis10--------
    rs798911101,2
    Cpathogenic12614110(+) TTAGCA/GGGTAA 42 R G int1 mis10--------
    rs1219127751,2
    Cpathogenic12659186(+) ACTGCA/GGGGCC 46 R G mis10--------
    rs344190501,2
    C,Fprobable-non-pathogenic12224511(-) GCTGCG/ATCGAT 46 /D syn13Minor allele frequency- A:0.02NA EU 853
    rs1882241141,2
    Cuntested12717707(+) CACACA/GGAAGA 46 T syn10--------

    HapMap Linkage Disequilibrium report for CACNA1C (2079952 - 2329952 bp, first 250kb of CACNA1C)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for CACNA1C (see all 80):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv1150716CNV Deletion17803354
    esv998408CNV Deletion20482838
    esv2745414CNV Deletion23290073
    esv2422127CNV Deletion20811451
    esv2665790CNV Deletion23128226
    esv2660122CNV Deletion23128226
    esv2745406CNV Deletion23290073
    esv2666981CNV Deletion23128226
    esv2745412CNV Deletion23290073
    esv2674294CNV Deletion23128226

    Human Gene Mutation Database (HGMD): CACNA1C
    Locus Specific Mutation Databases (LSDB): CACNA1C

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing CACNA1C
    DNA2.0 Custom Variant and Variant Library Synthesis for CACNA1C

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 114205   
    OMIM disorders: 601005  611875  
    UniProtKB/Swiss-Prot: CAC1C_HUMAN, Q13936
  • Timothy syndrome (TS) [MIM:601005]: Disorder characterized by multiorgan dysfunction including lethal
    arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia,
    cognitive abnormalities and autism. Note=The disease is caused by mutations affecting the gene represented in
    this entry
  • Brugada syndrome 3 (BRGDA3) [MIM:611875]: A heart disease characterized by the association of Brugada
    syndrome with shortened QT intervals. Brugada syndrome is a tachyarrhythmia characterized by right bundle branch
    block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that
    the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will
    faint and may die in a few minutes if the heart is not reset. Note=The disease is caused by mutations affecting
    the gene represented in this entry

  • 5 diseases for CACNA1C:    
    About MalaCards
    brugada syndrome 3    timothy syndrome    brugada syndrome 1    schizotypal personality disorder
    hypokalemic periodic paralysis

    6 diseases from the University of Copenhagen DISEASES database for CACNA1C:
    Timothy syndrome     Schizophrenia     Brugada syndrome     Long QT syndrome
    Autistic disorder     Schizotypal personality disorder

    Find genes that share disorders with CACNA1C           About GenesLikeMe

    1 Novoseek inferred disease relationship for CACNA1C gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    hypokalemic periodic paralysis 64.6 1 9436445 (1)

    GeneTests: CACNA1C
    GeneReviews: CACNA1C
    Genetic Association Database (GAD): CACNA1C
    Human Genome Epidemiology (HuGE) Navigator: CACNA1C (34 documents)

    Export disorders for CACNA1C gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CACNA1C gene, integrated from 10 sources (see all 275):
    (articles sorted by number of sources associating them with CACNA1C)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human alpha1C subunit gene. (PubMed id 9607315)1, 2, 7 Zuehlke R.D.... Reuter H. (FEBS Lett. 1998)
    2. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. (PubMed id 15863612)1, 2, 9 Splawski I.... Keating M.T. (Proc. Natl. Acad. Sci. U.S.A. 2005)
    3. Genetic polymorphisms of L-type calcium channel alpha1C and alpha1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers. (PubMed id 19225208)1, 4, 9 Kamide K....Kawano Y. (Circ. J. 2009)
    4. Assignment of the human gene for the alpha 1 subunit of the cardiac DHP-sensitive Ca2+ channel (CCHL1A1) to chromosome 12p12-pter. (PubMed id 1653763)1, 2, 9 Powers P.A.... Hogan K. (Genomics 1991)
    5. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. (PubMed id 17224476)1, 2, 9 Antzelevitch C.... Wolpert C. (Circulation 2007)
    6. A novel long N-terminal isoform of human L-type Ca2+ channel is up- regulated by protein kinase C. (PubMed id 11741969)1, 2, 9 Blumenstein Y....Dascal N. (J. Biol. Chem. 2002)
    7. Genome-wide association study identifies five new schizophrenia loci. (PubMed id 21926974)1, 4 (Nat. Genet. 2011)
    8. Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder. (PubMed id 20351715)1, 4 Liu Y....Sullivan P.F. (Mol. Psychiatry 2011)
    9. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. (PubMed id 21926972)1, 4 (Nat. Genet. 2011)
    10. Genetic variation in CACNA1C affects brain circuitries related to mental illness. (PubMed id 20819988)1, 4 Bigos K.L....Weinberger D.R. (Arch. Gen. Psychiatry 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 775 HGNC: 1390 AceView: CACNA1C Ensembl:ENSG00000151067 euGenes: HUgn775
    ECgene: CACNA1C Kegg: 775 H-InvDB: CACNA1C

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for CACNA1C Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=CACNA1C[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CACNA1C gene:
    Search GeneIP for patents involving CACNA1C

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from genOway)
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