Human Gene CACNA1C (ENST00000347598.9) Description and Page Index
  Description: Homo sapiens calcium voltage-gated channel subunit alpha1 C (CACNA1C), transcript variant 1, mRNA. (from RefSeq NM_199460)
RefSeq Summary (NM_001129827): 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].
Gencode Transcript: ENST00000347598.9
Gencode Gene: ENSG00000151067.22
Transcript (Including UTRs)
   Position: hg38 chr12:2,052,987-2,697,950 Size: 644,964 Total Exon Count: 49 Strand: +
Coding Region
   Position: hg38 chr12:2,053,563-2,691,199 Size: 637,637 Coding Exon Count: 49 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:2,052,987-2,697,950)mRNA (may differ from genome)Protein (2186 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGImyGene2neXtProtOMIM
PubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: CAC1C_HUMAN
DESCRIPTION: RecName: Full=Voltage-dependent L-type calcium channel subunit alpha-1C; AltName: Full=Calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle; AltName: Full=Voltage-gated calcium channel subunit alpha Cav1.2;
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.
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).
INTERACTION: Q9NZU7:CABP1; NbExp=4; IntAct=EBI-1038838, EBI-907894; P62158:CALM3; NbExp=2; IntAct=EBI-1038838, EBI-397435;
SUBCELLULAR LOCATION: 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).
TISSUE SPECIFICITY: Expressed in brain, heart, jejunum, ovary, pancreatic beta-cells and vascular smooth muscle. Overall expression is reduced in atherosclerotic vascular smooth muscle.
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).
PTM: Phosphorylation by PKA activates the channel (By similarity).
DISEASE: Defects in CACNA1C are the cause of Timothy syndrome (TS) [MIM:601005]. TS is a disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities and autism.
DISEASE: Defects in CACNA1C are the cause of Brugada syndrome type 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 (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset.
SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1C subfamily.
SEQUENCE CAUTION: Sequence=AAA02500.2; Type=Frameshift; Positions=1844;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CACNA1C";

-  MalaCards Disease Associations
  MalaCards Gene Search: CACNA1C
Diseases sorted by gene-association score: timothy syndrome* (1700), brugada syndrome 3* (1329), brugada syndrome* (563), long qt syndrome* (190), familial long qt syndrome* (151), schizotypal personality disorder (13), diabetic cataract (10), hypokalemic periodic paralysis, type 1 (10), high pressure neurological syndrome (8), right bundle branch block (7), short qt syndrome (7), mood disorder (6), jervell and lange-nielsen syndrome (5), hypertrichotic osteochondrodysplasia cantu type (5), hyperphenylalaninemia (4), long qt syndrome 6 (4), long qt syndrome 1 (3), autism spectrum disorder (2), schizophrenia (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 18.92 RPKM in Colon - Sigmoid
Total median expression: 171.18 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -248.90576-0.432 Picture PostScript Text
3' UTR -2228.206751-0.330 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR005821 - Ion_trans_dom
IPR014873 - VDCC_a1su_IQ
IPR005451 - VDCC_L_a1csu
IPR005446 - VDCC_L_a1su
IPR002077 - VDCCAlpha1

Pfam Domains:
PF08763 - Voltage gated calcium channel IQ domain
PF00520 - Ion transport protein

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1T0J
- X-ray MuPIT

2BE6
- X-ray MuPIT

2F3Y
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2F3Z - X-ray MuPIT 2LQC - NMR MuPIT 3G43 - X-ray MuPIT
3OXQ - X-ray


ModBase Predicted Comparative 3D Structure on Q13936
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005216 ion channel activity
GO:0005244 voltage-gated ion channel activity
GO:0005245 voltage-gated calcium channel activity
GO:0005262 calcium channel activity
GO:0005515 protein binding
GO:0005516 calmodulin binding
GO:0008331 high voltage-gated calcium channel activity
GO:0046872 metal ion binding
GO:0051393 alpha-actinin binding
GO:0086007 voltage-gated calcium channel activity involved in cardiac muscle cell action potential
GO:0086056 voltage-gated calcium channel activity involved in AV node cell action potential

Biological Process:
GO:0002520 immune system development
GO:0006811 ion transport
GO:0006816 calcium ion transport
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007507 heart development
GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
GO:0034765 regulation of ion transmembrane transport
GO:0035115 embryonic forelimb morphogenesis
GO:0035585 calcium-mediated signaling using extracellular calcium source
GO:0043010 camera-type eye development
GO:0050796 regulation of insulin secretion
GO:0055085 transmembrane transport
GO:0060402 calcium ion transport into cytosol
GO:0061337 cardiac conduction
GO:0061577 calcium ion transmembrane transport via high voltage-gated calcium channel
GO:0070588 calcium ion transmembrane transport
GO:0086002 cardiac muscle cell action potential involved in contraction
GO:0086012 membrane depolarization during cardiac muscle cell action potential
GO:0086045 membrane depolarization during AV node cell action potential
GO:0086064 cell communication by electrical coupling involved in cardiac conduction
GO:0086091 regulation of heart rate by cardiac conduction
GO:0098911 regulation of ventricular cardiac muscle cell action potential
GO:0098912 membrane depolarization during atrial cardiac muscle cell action potential

Cellular Component:
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0005891 voltage-gated calcium channel complex
GO:0014069 postsynaptic density
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030018 Z disc
GO:1990454 L-type voltage-gated calcium channel complex


-  Descriptions from all associated GenBank mRNAs
  AK309111 - Homo sapiens cDNA, FLJ99152.
AF465484 - Homo sapiens jejunum L-type calcium channel alpha1C subunit mRNA, complete cds.
AK308652 - Homo sapiens cDNA, FLJ98693.
BC146846 - Homo sapiens calcium channel, voltage-dependent, L type, alpha 1C subunit, mRNA (cDNA clone MGC:181949 IMAGE:9056774), complete cds.
AB209016 - Homo sapiens mRNA for Voltage-dependent L-type calcium channel alpha-1C subunit variant protein.
AJ224873 - Homo sapiens (HLCC105) mRNA for voltage-dependent L-type calcium channel alpha-1C subunit (splice variant).
AY830711 - Homo sapiens clone HLCC125 voltage-dependent L-type calcium channel alpha-1C subunit splice variant mRNA, complete cds, alternatively spliced.
AY830712 - Homo sapiens clone HLCC127 voltage-dependent L-type calcium channel alpha-1C subunit splice variant mRNA, complete cds, alternatively spliced.
AY830713 - Homo sapiens clone HLCC126 voltage-dependent L-type calcium channel alpha-1C subunit splice variant mRNA, complete cds, alternatively spliced.
Z34809 - H.sapiens (HLCC69) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34810 - H.sapiens (HLCC70) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34811 - H.sapiens (HLCC71) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34812 - H.sapiens (HLCC73) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34813 - H.sapiens (HLCC74) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34814 - H.sapiens (HLCC76) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34815 - H.sapiens (HLCC77) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34816 - H.sapiens (HLCC78) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34817 - H.sapiens (HLCC86) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34818 - H.sapiens (HLCC87) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34819 - H.sapiens (HLCC88) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34820 - H.sapiens (HLCC89) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34821 - H.sapiens (HLCC90) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z34822 - H.sapiens (HLCC85) mRNA for voltage-dependent L-type Ca channel alpha 1 subunit (splice variant).
Z74996 - H.sapiens mRNA for voltage-dependent L-type calcium channel, alpha 1C subunit (splice variant).
L04569 - Homo sapiens (clone hHT-1) L-type voltage-dependent calcium channel a1 subunit (hHT) mRNA, complete cds.
L29529 - Homo sapiens (clone HHT-1 variant harboring HH-05) cardiac L-type voltage dependent calcium channel alpha 1 subunit (CACNL1A1) mRNA, complete cds.
L29534 - Homo sapiens cardiac L-type voltage-dependent calcium channel a1 subunit (CACNL1A1) mRNA, complete cds.
L29536 - Homo sapiens calcium channel L-type alpha 1 subunit (CACNL1A1) mRNA, complete cds.
Z26295 - H.sapiens mRNA for L-type calcium channel isoform 1, neuronal subform (partial).
M57971 - Human cardiac L-type calcium channel (CCHL1A1) mRNA, partial cds.
M57972 - Human cardiac muscle L-type calcium channel alpha-1 (CCHL1A1) mRNA, partial cds.
A22922 - H.sapiens mRNA fragment (p1247-9.1.1.2).
A22930 - H.sapiens mRNA fragment (pR9112-10.1.1.1).
JD191987 - Sequence 173011 from Patent EP1572962.
JD151667 - Sequence 132691 from Patent EP1572962.
JD287250 - Sequence 268274 from Patent EP1572962.
AY562396 - Homo sapiens voltage-gated L-type calcium channel Cav1.2 alpha 1 subunit, splice variant 10* (CACNA1C) mRNA, partial cds, alternatively spliced.
AY562395 - Homo sapiens voltage-gated L-type calcium channel Cav1.2 alpha 1 subunit, splice variant 9* (CACNA1C) mRNA, partial cds, alternatively spliced.
AJ536834 - Homo sapiens partial mRNA for voltage-dependent L-type calcium channel alpha 1C subunit (CACNA1C gene), long splice variant.
AJ537510 - Homo sapiens partial mRNA for voltage-dependent L-type calcium channel alpha 1C subunit (CACNA1C gene), normal splice variant.
AK302698 - Homo sapiens cDNA FLJ50301 complete cds, highly similar to Voltage-dependent L-type calcium channel subunit alpha-1C.
AK098681 - Homo sapiens cDNA FLJ25815 fis, clone TST07482.
A22934 - H.sapiens mRNA fragment (pR9112-2.1.1.1).
A22928 - H.sapiens mRNA fragment (pR9112-4.1.1.1).
Z26294 - H.sapiens mRNA for L-type calcium channel isoform 1, neuronal subform (partial).
AF070589 - Homo sapiens clones 24595 and 24808 calcium channel L-type alpha 1 subunit mRNA, partial cds.
JD143058 - Sequence 124082 from Patent EP1572962.
JD566524 - Sequence 547548 from Patent EP1572962.
JD520637 - Sequence 501661 from Patent EP1572962.
JD470829 - Sequence 451853 from Patent EP1572962.
JD339398 - Sequence 320422 from Patent EP1572962.
JD210583 - Sequence 191607 from Patent EP1572962.
JD466684 - Sequence 447708 from Patent EP1572962.
JD280263 - Sequence 261287 from Patent EP1572962.
JD490344 - Sequence 471368 from Patent EP1572962.
JD283422 - Sequence 264446 from Patent EP1572962.
JD126236 - Sequence 107260 from Patent EP1572962.
JD050935 - Sequence 31959 from Patent EP1572962.
AY129012 - Homo sapiens clone FP17720 unknown mRNA.
AK092125 - Homo sapiens cDNA FLJ34806 fis, clone NT2NE2006659.
AX747366 - Sequence 891 from Patent EP1308459.
JD439151 - Sequence 420175 from Patent EP1572962.
JD336252 - Sequence 317276 from Patent EP1572962.
JD392838 - Sequence 373862 from Patent EP1572962.
JD554611 - Sequence 535635 from Patent EP1572962.
JD391450 - Sequence 372474 from Patent EP1572962.
JD202413 - Sequence 183437 from Patent EP1572962.
JD516363 - Sequence 497387 from Patent EP1572962.
JD328787 - Sequence 309811 from Patent EP1572962.
JD511265 - Sequence 492289 from Patent EP1572962.
JD208149 - Sequence 189173 from Patent EP1572962.
JD181069 - Sequence 162093 from Patent EP1572962.
JD376502 - Sequence 357526 from Patent EP1572962.
JD038127 - Sequence 19151 from Patent EP1572962.
JD096685 - Sequence 77709 from Patent EP1572962.
JD043246 - Sequence 24270 from Patent EP1572962.
BC093695 - Homo sapiens calcium channel, voltage-dependent, L type, alpha 1C subunit, mRNA (cDNA clone IMAGE:7939540), complete cds.
JD065535 - Sequence 46559 from Patent EP1572962.
JD045480 - Sequence 26504 from Patent EP1572962.
JD371526 - Sequence 352550 from Patent EP1572962.
JD056666 - Sequence 37690 from Patent EP1572962.
JD083358 - Sequence 64382 from Patent EP1572962.
JD464767 - Sequence 445791 from Patent EP1572962.
JD317238 - Sequence 298262 from Patent EP1572962.
JD329965 - Sequence 310989 from Patent EP1572962.
JD213794 - Sequence 194818 from Patent EP1572962.
JD513306 - Sequence 494330 from Patent EP1572962.
JD475588 - Sequence 456612 from Patent EP1572962.
JD224328 - Sequence 205352 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04020 - Calcium signaling pathway
hsa04260 - Cardiac muscle contraction
hsa04270 - Vascular smooth muscle contraction
hsa04720 - Long-term potentiation
hsa04912 - GnRH signaling pathway
hsa04930 - Type II diabetes mellitus
hsa05010 - Alzheimer's disease
hsa05410 - Hypertrophic cardiomyopathy (HCM)
hsa05412 - Arrhythmogenic right ventricular cardiomyopathy (ARVC)
hsa05414 - Dilated cardiomyopathy

Reactome (by CSHL, EBI, and GO)

Protein Q13936 (Reactome details) participates in the following event(s):

R-HSA-525833 NCAM1 interacts with T- and L-type VDCC
R-HSA-265645 Calcium Influx through Voltage-gated Calcium Channels
R-HSA-5577213 LTCC heteropentamer (open) transports Ca2+ from extracellular region to cytosol
R-HSA-400042 Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-419037 NCAM1 interactions
R-HSA-422356 Regulation of insulin secretion
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-5576892 Phase 0 - rapid depolarisation
R-HSA-5576893 Phase 2 - plateau phase
R-HSA-163685 Energy Metabolism
R-HSA-422475 Axon guidance
R-HSA-5576891 Cardiac conduction
R-HSA-1430728 Metabolism
R-HSA-1266738 Developmental Biology
R-HSA-397014 Muscle contraction

-  Other Names for This Gene
  Alternate Gene Symbols: B2RUT3, CAC1C_HUMAN, CACH2, CACN2, CACNL1A1, CCHL1A1, NM_199460, Q13917, Q13918, Q13919, Q13920, Q13921, Q13922, Q13923, Q13924, Q13925, Q13926, Q13927, Q13928, Q13929, Q13930, Q13932, Q13933, Q13936, Q14743, Q14744, Q15877, Q4VMI7, Q4VMI8, Q4VMI9, Q6PKM7, Q8N6C0, Q99025, Q99241, Q99875, uc001qkl.1, uc001qkl.2, uc001qkl.3, uc001qkl.4
UCSC ID: uc001qkl.4
RefSeq Accession: NM_001129827
Protein: Q13936 (aka CAC1C_HUMAN or CCAC_HUMAN)
CCDS: CCDS44787.1, CCDS44788.1, CCDS44789.1, CCDS44790.1, CCDS44791.1, CCDS44792.1, CCDS44793.1, CCDS44794.1, CCDS44795.1, CCDS44796.1, CCDS44797.1, CCDS44798.1, CCDS44799.1, CCDS44800.1, CCDS44801.1, CCDS53733.1, CCDS53734.1, CCDS53735.1, CCDS53736.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene CACNA1C:
brugada (Brugada Syndrome)
rws (Long QT Syndrome)
timothy (Timothy Syndrome)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.