CACNA1C (calcium voltage-gated channel subunit alpha1 C)

Gene

• Entrez ID: 775
• Gene name: Calcium voltage-gated channel subunit alpha1 C
• Gene symbol: CACNA1C
• Synonyms: CACH2, CACN2, CACNL1A1, CCHL1A1, CaV1.2, LQT8, TS, TS. LQT8
• Chromosome: 12
• Chromosome location: 12p13.33
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs56394008	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs79891110	G>A,T	Pathogenic, not-provided	Stop gained, coding sequence variant, intron variant, missense variant
rs80315385	G>A,C	Pathogenic, not-provided, uncertain-significance	Coding sequence variant, intron variant, missense variant
rs111606207	C>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign, uncertain-significance	Coding sequence variant, synonymous variant, missense variant
rs121912775	G>A	Conflicting-interpretations-of-pathogenicity, benign, likely-benign, pathogenic	Coding sequence variant, missense variant
rs121912776	C>T	Pathogenic, not-provided	Coding sequence variant, missense variant
rs141633456	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, coding sequence variant
rs184684058	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs186741807	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity	Intron variant
rs200330469	C>T	Likely-benign, benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs200800133	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs201258230	C>A,T	Likely-benign, benign-likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs201345843	C>T	Benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs201756421	T>C	Likely-benign, uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs367895193	G>A,T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Intron variant, missense variant, coding sequence variant
rs369079645	A>G	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs370576211	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs372702466	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant
rs374857905	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, synonymous variant
rs375534041	A>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs398123517	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant
rs527741368	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant
rs545511851	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs575583988	GAG>-	Conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	Coding sequence variant, inframe deletion
rs587782933	G>A	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant, intron variant
rs730880056	G>A,C	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs747654175	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs750459136	C>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs750835733	C>G,T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs750998195	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs754527651	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs758786846	C>G,T	Pathogenic	Missense variant, coding sequence variant, stop gained
rs760888275	C>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs773528195	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs786205745	G>A,C	Pathogenic	Intron variant, missense variant, coding sequence variant
rs786205748	C>T	Pathogenic	Missense variant, coding sequence variant
rs786205753	G>A	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs794727587	C>G	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs797044881	T>C	Pathogenic	Missense variant, coding sequence variant
rs886042224	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, intron variant, missense variant
rs1057517711	G>A	Uncertain-significance, likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1467561684	A>G,T	Likely-pathogenic	Missense variant, coding sequence variant
rs1555672574	G>A	Likely-pathogenic	Stop gained, coding sequence variant
rs1555836187	A>G,T	Pathogenic	Missense variant, stop gained, coding sequence variant
rs1555968941	G>A,C	Not-provided, likely-pathogenic	Missense variant, coding sequence variant
rs1568469857	C>A	Pathogenic	Missense variant, coding sequence variant
rs1569139160	C>G	Pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT001203	hsa-miR-133a-3p	Luciferase reporter assay, Western blot	19136465
MIRT444931	hsa-miR-5006-3p	PAR-CLIP	22100165
MIRT444932	hsa-miR-4755-5p	PAR-CLIP	22100165
MIRT444933	hsa-miR-211-5p	PAR-CLIP	22100165
MIRT444934	hsa-miR-204-5p	PAR-CLIP	22100165
MIRT444935	hsa-miR-623	PAR-CLIP	22100165
MIRT444936	hsa-miR-4780	PAR-CLIP	22100165
MIRT444937	hsa-miR-6780b-3p	PAR-CLIP	22100165
MIRT444938	hsa-miR-3938	PAR-CLIP	22100165
MIRT568955	hsa-miR-6791-5p	PAR-CLIP	20371350
MIRT568956	hsa-miR-6778-5p	PAR-CLIP	20371350
MIRT568957	hsa-miR-450a-2-3p	PAR-CLIP	20371350
MIRT568958	hsa-miR-6857-5p	PAR-CLIP	20371350
MIRT568959	hsa-miR-6763-5p	PAR-CLIP	20371350
MIRT568960	hsa-miR-3150a-3p	PAR-CLIP	20371350
MIRT568961	hsa-miR-6810-5p	PAR-CLIP	20371350
MIRT568962	hsa-miR-2110	PAR-CLIP	20371350
MIRT568963	hsa-miR-3147	PAR-CLIP	20371350
MIRT568964	hsa-miR-4425	PAR-CLIP	20371350
MIRT568965	hsa-miR-185-3p	PAR-CLIP	20371350
MIRT568966	hsa-miR-4283	PAR-CLIP	20371350
MIRT568967	hsa-miR-4489	PAR-CLIP	20371350
MIRT568968	hsa-miR-6825-5p	PAR-CLIP	20371350
MIRT568969	hsa-miR-939-5p	PAR-CLIP	20371350
MIRT568970	hsa-miR-1343-5p	PAR-CLIP	20371350
MIRT568971	hsa-miR-3175	PAR-CLIP	20371350
MIRT568972	hsa-miR-5001-5p	PAR-CLIP	20371350
MIRT568973	hsa-miR-762	PAR-CLIP	20371350
MIRT568974	hsa-miR-4498	PAR-CLIP	20371350
MIRT568975	hsa-miR-4492	PAR-CLIP	20371350
MIRT568976	hsa-miR-7106-5p	PAR-CLIP	20371350
MIRT568977	hsa-miR-920	PAR-CLIP	20371350
MIRT568978	hsa-miR-6726-5p	PAR-CLIP	20371350
MIRT568979	hsa-miR-5591-5p	PAR-CLIP	20371350
MIRT568980	hsa-miR-4300	PAR-CLIP	20371350
MIRT568981	hsa-miR-5787	PAR-CLIP	20371350
MIRT568982	hsa-miR-4505	PAR-CLIP	20371350
MIRT568983	hsa-miR-4731-5p	PAR-CLIP	20371350
MIRT568984	hsa-miR-6754-5p	PAR-CLIP	20371350
MIRT568985	hsa-miR-4487	PAR-CLIP	20371350
MIRT568986	hsa-miR-4441	PAR-CLIP	20371350
MIRT568987	hsa-miR-4270	PAR-CLIP	20371350
MIRT732349	hsa-miR-29a-3p	Luciferase reporter assay, qRT-PCR, Western blot	27341015
MIRT732875	hsa-miR-208a-3p	Luciferase reporter assay	27545043
MIRT732876	hsa-miR-208b-3p	Luciferase reporter assay	27545043
MIRT734744	hsa-miR-103a-3p	Immunocytochemistry, qRT-PCR, Western blot	25627864

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002520	Process	Immune system development	IMP	15454078
GO:0005245	Function	Voltage-gated calcium channel activity	IBA	21873635
GO:0005245	Function	Voltage-gated calcium channel activity	IDA	8392192, 12130699
GO:0005245	Function	Voltage-gated calcium channel activity	IMP	24728418
GO:0005515	Function	Protein binding	IPI	11438518, 15140941, 18535142
GO:0005516	Function	Calmodulin binding	IPI	15140941
GO:0005737	Component	Cytoplasm	IDA	11206130
GO:0005886	Component	Plasma membrane	IDA	11206130
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	ISS
GO:0005891	Component	Voltage-gated calcium channel complex	IDA	12130699, 17224476
GO:0006816	Process	Calcium ion transport	IBA	21873635
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IDA	12130699
GO:0007507	Process	Heart development	IMP	15454078
GO:0008331	Function	High voltage-gated calcium channel activity	IBA	21873635
GO:0008331	Function	High voltage-gated calcium channel activity	IDA	15454078
GO:0008331	Function	High voltage-gated calcium channel activity	TAS	11576544
GO:0010881	Process	Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	ISS
GO:0010881	Process	Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	TAS	11576544
GO:0014069	Component	Postsynaptic density	IDA	14140941
GO:0016021	Component	Integral component of membrane	IDA	8392192
GO:0016032	Process	Viral process	IEA
GO:0030018	Component	Z disc	ISS
GO:0030425	Component	Dendrite	IEA
GO:0035115	Process	Embryonic forelimb morphogenesis	IMP	15454078
GO:0035585	Process	Calcium-mediated signaling using extracellular calcium source	TAS	11576544
GO:0043010	Process	Camera-type eye development	IMP	15454078
GO:0043204	Component	Perikaryon	IEA
GO:0045762	Process	Positive regulation of adenylate cyclase activity	ISS
GO:0046872	Function	Metal ion binding	IEA
GO:0050796	Process	Regulation of insulin secretion	TAS
GO:0051393	Function	Alpha-actinin binding	IPI	17110593
GO:0060402	Process	Calcium ion transport into cytosol	ISS
GO:0060402	Process	Calcium ion transport into cytosol	TAS	19095005
GO:0061337	Process	Cardiac conduction	IMP	24728418
GO:0061337	Process	Cardiac conduction	TAS
GO:0061577	Process	Calcium ion transmembrane transport via high voltage-gated calcium channel	IDA	15454078
GO:0070509	Process	Calcium ion import	IBA	21873635
GO:0070588	Process	Calcium ion transmembrane transport	IDA	15454078
GO:0070588	Process	Calcium ion transmembrane transport	IMP	24728418
GO:0086002	Process	Cardiac muscle cell action potential involved in contraction	IMP	15454078
GO:0086007	Function	Voltage-gated calcium channel activity involved in cardiac muscle cell action potential	IMP	15454078
GO:0086007	Function	Voltage-gated calcium channel activity involved in cardiac muscle cell action potential	IMP	17224476
GO:0086012	Process	Membrane depolarization during cardiac muscle cell action potential	IMP	15454078
GO:0086045	Process	Membrane depolarization during AV node cell action potential	IMP	26253506
GO:0086056	Function	Voltage-gated calcium channel activity involved in AV node cell action potential	IMP	26253506
GO:0086064	Process	Cell communication by electrical coupling involved in cardiac conduction	TAS	11576544
GO:0086091	Process	Regulation of heart rate by cardiac conduction	IMP	15454078, 15863612, 17224476, 26253506
GO:0098839	Component	Postsynaptic density membrane	IEA
GO:0098911	Process	Regulation of ventricular cardiac muscle cell action potential	IMP	15454078, 26253506
GO:0098912	Process	Membrane depolarization during atrial cardiac muscle cell action potential	IMP	17224476
GO:1990454	Component	L-type voltage-gated calcium channel complex	IDA	15454078

Other IDs

• MIM: 114205
• HGNC: 1390
• e!Ensembl: ENSG00000151067

Protein

• UniProt ID: Q13936
• Protein name: Voltage-dependent L-type calcium channel subunit alpha-1C (Calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle) (Voltage-gated calcium channel subunit alpha Cav1.2)
• Protein function: Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:8392192, PubMed:7737988, PubMed:9087614, PubMed:9013606, PubMed:9607315, PubMed:12176756, PubMed:17071743, PubMed:11741969, PubMed:8099908, PubMed:12181424, PubMed:29078335, PubMed:29742403, PubMed:16299511, PubMed:20953164, PubMed:15454078, PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506, PubMed:27218670, PubMed:23677916). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm (PubMed:15454078, PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (PubMed:28119464). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable). ; (Microbial infection) Acts as a receptor for Influenzavirus (PubMed:29779930). May play a critical role in allowing virus entry when sialylated and expressed on lung tissues (PubMed:29779930).
• PDB: 1T0J, 2BE6, 2F3Y, 2F3Z, 2LQC, 3G43, 3OXQ, 5V2P, 5V2Q, 6C0A, 6DAD, 6DAE, 6DAF, 6U39, 6U3A, 6U3B, 6U3D
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00520	Ion_trans	123 → 416	Ion transport protein	Family
  PF00520	Ion_trans	523 → 764	Ion transport protein	Family
  PF00520	Ion_trans	899 → 955	Ion transport protein	Family
  PF00520	Ion_trans	951 → 1197	Ion transport protein	Family
  PF00520	Ion_trans	1238 → 1324	Ion transport protein	Family
  PF00520	Ion_trans	1320 → 1535	Ion transport protein	Family
  PF16905	GPHH	1544 → 1597	Voltage-dependent L-type calcium channel, IQ-associated	Family
  PF08763	Ca_chan_IQ	1607 → 1681	Voltage gated calcium channel IQ domain	Domain
  PF16885	CAC1F_C	1701 → 1819	Voltage-gated calcium channel subunit alpha, C-term	Family
  PF16885	CAC1F_C	2080 → 2190	Voltage-gated calcium channel subunit alpha, C-term	Family

• Sequence:

  MVNENTRMYIPEENHQGSNYGSPRPAHANMNANAAAGLAPEHIPTPGAALSWQAAIDAAR
  QAKLMGSAGNATISTVSSTQRKRQQYGKPKKQGSTTATRPPRALLCLTLKNPIRRACISI
  VEWKPFEIIILLTIFANCVALAIYIPFPEDDSNATNSNLERVEYLFLIIFTVEAFLKVIA
  YGLLFHPNAYLRNGWNLLDFIIVVVGLFSAILEQATKADGANALGGKGAGFDVKALRAFR
  VLRPLRLVSGVPSLQVVLNSIIKAMVPLLHIALLVLFVIIIYAIIGLELFMGKMHKTCYN
  QEGIADVPAEDDPSPCALETGHGRQCQNGTVCKPGWDGPKHGITNFDNFAFAMLTVFQCI
  TMEGWTDVLYWVNDAVGRDWPWIYFVTLIIIGSFFVLNLVLGVLSGEFSKEREKAKARGD
  FQKLREKQQLEEDLKGYLDWITQAEDIDPENEDEGMDEEKPRNMSMPTSETESVNTENVA
  GGDIEGENCGARLAHRISKSKFSRYWRRWNRFCRRKCRAAVKSNVFYWLVIFLVFLNTLT
  IASEHYNQPNWLTEVQDTANKALLALFTAEMLLKMYSLGLQAYFVSLFNRFDCFVVCGGI
  LETILVETKIMSPLGISVLRCVRLLRIFKITRYWNSLSNLVASLLNSVRSIASLLLLLFL
  FIIIFSLLGMQLFGGKFNFDEMQTRRSTFDNFPQSLLTVFQILTGEDWNSVMYDGIMAYG
  GPSFPGMLVCIYFIILFICGNYILLNVFLAIAVDNLADAESLTSAQKEEEEEKERKKLAR
  TASPEKKQELVEKPAVGESKEEKIELKSITADGESPPATKINMDDLQPNENEDKSPYPNP
  ETTGEEDEEEPEMPVGPRPRPLSELHLKEKAVPMPEASAFFIFSSNNRFRLQCHRIVNDT
  IFTNLILFFILLSSISLAAEDPVQHTSFRNHILFYFDIVFTTIFTIEIALKILGNADYVF
  TSIFTLEIILKMTAYGAFLHKGSFCRNYFNILDLLVVSVSLISFGIQSSAINVVKILRVL
  RVLRPLRAINRAKGLKHVVQCVFVAIRTIGNIVIVTTLLQFMFACIGVQLFKGKLYTCSD
  SSKQTEAECKGNYITYKDGEVDHPIIQPRSWENSKFDFDNVLAAMMALFTVSTFEGWPEL
  LYRSIDSHTEDKGPIYNYRVEISIFFIIYIIIIAFFMMNIFVGFVIVTFQEQGEQEYKNC
  ELDKNQRQCVEYALKARPLRRYIPKNQHQYKVWYVVNSTYFEYLMFVLILLNTICLAMQH
  YGQSCLFKIAMNILNMLFTGLFTVEMILKLIAFKPKGYFSDPWNVFDFLIVIGSIIDVIL
  SETNHYFCDAWNTFDALIVVGSIVDIAITEVNPAEHTQCSPSMNAEENSRISITFFRLFR
  VMRLVKLLSRGEGIRTLLWTFIKSFQALPYVALLIVMLFFIYAVIGMQVFGKIALNDTTE
  INRNNNFQTFPQAVLLLFRCATGEAWQDIMLACMPGKKCAPESEPSNSTEGETPCGSSFA
  VFYFISFYMLCAFLIINLFVAVIMDNFDYLTRDWSILGPHHLDEFKRIWAEYDPEAKGRI
  KHLDVVTLLRRIQPPLGFGKLCPHRVACKRLVSMNMPLNSDGTVMFNATLFALVRTALRI
  KTEGNLEQANEELRAIIKKIWKRTSMKLLDQVVPPAGDDEVTVGKFYATFLIQEYFRKFK
  KRKEQGLVGKPSQRNALSLQAGLRTLHDIGPEIRRAISGDLTAEEELDKAMKEAVSAASE
  DDIFRRAGGLFGNHVSYYQSDGRSAFPQTFTTQRPLHINKAGSSQGDTESPSHEKLVDST
  FTPSSYSSTGSNANINNANNTALGRLPRPAGYPSTVSTVEGHGPPLSPAIRVQEVAWKLS
  SNRERHVPMCEDLELRRDSGSAGTQAHCLLLRKANPSRCHSRESQAAMAGQEETSQDETY
  EVKMNHDTEACSEPSLLSTEMLSYQDDENRQLTLPEEDKRDIRQSPKRGFLRSASLGRRA
  SFHLECLKRQKDRGGDISQKTVLPLHLVHHQALAVAGLSPLLQRSHSPASFPRPFATPPA
  TPGSRGWPPQPVPTLRLEGVESSEKLNSSFPSIHCGSWAETTPGGGGSSAARRVRPVSLM
  VPSQAGAPGRQFHGSASSLVEAVLISEGLGQFAQDPKFIEVTTQELADACDMTIEEMESA
  ADNILSGGAPQSPNGALLPFVNCRDAGQDRAGGEEDAGCVRARGRPSEEELQDSRVYVSS
  L

• Sequence length: 2221