CACNA1D (calcium voltage-gated channel subunit alpha1 D)

Gene

• Entrez ID: 776
• Gene name: Calcium voltage-gated channel subunit alpha1 D
• Gene symbol: CACNA1D
• Synonyms: CACH3, CACN4, CACNL1A2, CCHL1A2, Cav1.3, PASNA, SANDD
• Chromosome: 3
• Chromosome location: 3p21.1
• Summary: Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, namely alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs35874056	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs41276445	C>A,G,T	Likely-pathogenic, pathogenic, likely-benign, uncertain-significance	Coding sequence variant, synonymous variant, missense variant
rs146747080	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity, benign	Coding sequence variant, synonymous variant
rs150266932	G>A,C	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant
rs186968009	T>G	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs375811590	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant
rs386834263	G>C	Likely-pathogenic	Missense variant, coding sequence variant, intron variant
rs386834264	G>A	Likely-pathogenic, pathogenic-likely-pathogenic	Missense variant, coding sequence variant, intron variant
rs398122827	->GGG	Pathogenic	Inframe insertion, coding sequence variant, intron variant
rs759274321	C>T	Pathogenic	Intron variant, missense variant, coding sequence variant
rs1064794938	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1553676901	G>C	Likely-pathogenic	Splice donor variant
rs1576484361	A>T	Likely-pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT441027	hsa-miR-136-5p	HITS-CLIP	24374217

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005245	Function	Voltage-gated calcium channel activity	IBA	21873635
GO:0005245	Function	Voltage-gated calcium channel activity	IDA	11160515, 21131953
GO:0005262	Function	Calcium channel activity	IMP	25620733, 28472301
GO:0005515	Function	Protein binding	IPI	30058071
GO:0005886	Component	Plasma membrane	ISS	21859974
GO:0005886	Component	Plasma membrane	TAS
GO:0005891	Component	Voltage-gated calcium channel complex	IDA	11160515
GO:0006816	Process	Calcium ion transport	IBA	21873635
GO:0006816	Process	Calcium ion transport	IDA	11160515
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	ISS
GO:0007605	Process	Sensory perception of sound	IMP	21131953
GO:0008331	Function	High voltage-gated calcium channel activity	IDA	1309651
GO:0030018	Component	Z disc	ISS
GO:0030506	Function	Ankyrin binding	ISS	21859974
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:0051928	Process	Positive regulation of calcium ion transport	IDA	1309651
GO:0060372	Process	Regulation of atrial cardiac muscle cell membrane repolarization	ISS
GO:0061337	Process	Cardiac conduction	TAS
GO:0070509	Process	Calcium ion import	IBA	21873635
GO:0070509	Process	Calcium ion import	IDA	1309651
GO:0070588	Process	Calcium ion transmembrane transport	ISS
GO:0086002	Process	Cardiac muscle cell action potential involved in contraction	IMP	21131953
GO:0086007	Function	Voltage-gated calcium channel activity involved in cardiac muscle cell action potential	IC	21859974
GO:0086012	Process	Membrane depolarization during cardiac muscle cell action potential	IC	21859974
GO:0086046	Process	Membrane depolarization during SA node cell action potential	IMP	21131953
GO:0086059	Function	Voltage-gated calcium channel activity involved SA node cell action potential	IMP	21131953
GO:0086091	Process	Regulation of heart rate by cardiac conduction	IMP	21131953
GO:0098793	Component	Presynapse	IEA
GO:1901016	Process	Regulation of potassium ion transmembrane transporter activity	ISS
GO:1901379	Process	Regulation of potassium ion transmembrane transport	ISS
GO:1990454	Component	L-type voltage-gated calcium channel complex	IDA	1309651

Other IDs

• MIM: 114206
• HGNC: 1391
• e!Ensembl: ENSG00000157388

Protein

• UniProt ID: Q01668
• Protein name: Voltage-dependent L-type calcium channel subunit alpha-1D (Calcium channel, L type, alpha-1 polypeptide, isoform 2) (Voltage-gated calcium channel subunit alpha Cav1.3)
• Protein 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-1D 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, and by benzothiazepines.
• PDB: 3LV3
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00520	Ion_trans	125 → 417	Ion transport protein	Family
  PF00520	Ion_trans	522 → 762	Ion transport protein	Family
  PF00520	Ion_trans	885 → 1163	Ion transport protein	Family
  PF00520	Ion_trans	1204 → 1475	Ion transport protein	Family
  PF16905	GPHH	1484 → 1537	Voltage-dependent L-type calcium channel, IQ-associated	Family
  PF08763	Ca_chan_IQ	1547 → 1621	Voltage gated calcium channel IQ domain	Domain
  PF16885	CAC1F_C	1642 → 1962	Voltage-gated calcium channel subunit alpha, C-term	Family
  PF16885	CAC1F_C	1965 → 2160	Voltage-gated calcium channel subunit alpha, C-term	Family

• Sequence:

  MMMMMMMKKMQHQRQQQADHANEANYARGTRLPLSGEGPTSQPNSSKQTVLSWQAAIDAA
  RQAKAAQTMSTSAPPPVGSLSQRKRQQYAKSKKQGNSSNSRPARALFCLSLNNPIRRACI
  SIVEWKPFDIFILLAIFANCVALAIYIPFPEDDSNSTNHNLEKVEYAFLIIFTVETFLKI
  IAYGLLLHPNAYVRNGWNLLDFVIVIVGLFSVILEQLTKETEGGNHSSGKSGGFDVKALR
  AFRVLRPLRLVSGVPSLQVVLNSIIKAMVPLLHIALLVLFVIIIYAIIGLELFIGKMHKT
  CFFADSDIVAEEDPAPCAFSGNGRQCTANGTECRSGWVGPNGGITNFDNFAFAMLTVFQC
  ITMEGWTDVLYWMNDAMGFELPWVYFVSLVIFGSFFVLNLVLGVLSGEFSKEREKAKARG
  DFQKLREKQQLEEDLKGYLDWITQAEDIDPENEEEGGEEGKRNTSMPTSETESVNTENVS
  GEGENRGCCGSLCQAISKSKLSRRWRRWNRFNRRRCRAAVKSVTFYWLVIVLVFLNTLTI
  SSEHYNQPDWLTQIQDIANKVLLALFTCEMLVKMYSLGLQAYFVSLFNRFDCFVVCGGIT
  ETILVELEIMSPLGISVFRCVRLLRIFKVTRHWTSLSNLVASLLNSMKSIASLLLLLFLF
  IIIFSLLGMQLFGGKFNFDETQTKRSTFDNFPQALLTVFQILTGEDWNAVMYDGIMAYGG
  PSSSGMIVCIYFIILFICGNYILLNVFLAIAVDNLADAESLNTAQKEEAEEKERKKIARK
  ESLENKKNNKPEVNQIANSDNKVTIDDYREEDEDKDPYPPCDVPVGEEEEEEEEDEPEVP
  AGPRPRRISELNMKEKIAPIPEGSAFFILSKTNPIRVGCHKLINHHIFTNLILVFIMLSS
  AALAAEDPIRSHSFRNTILGYFDYAFTAIFTVEILLKMTTFGAFLHKGAFCRNYFNLLDM
  LVVGVSLVSFGIQSSAISVVKILRVLRVLRPLRAINRAKGLKHVVQCVFVAIRTIGNIMI
  VTTLLQFMFACIGVQLFKGKFYRCTDEAKSNPEECRGLFILYKDGDVDSPVVRERIWQNS
  DFNFDNVLSAMMALFTVSTFEGWPALLYKAIDSNGENIGPIYNHRVEISIFFIIYIIIVA
  FFMMNIFVGFVIVTFQEQGEKEYKNCELDKNQRQCVEYALKARPLRRYIPKNPYQYKFWY
  VVNSSPFEYMMFVLIMLNTLCLAMQHYEQSKMFNDAMDILNMVFTGVFTVEMVLKVIAFK
  PKGYFSDAWNTFDSLIVIGSIIDVALSEADPTESENVPVPTATPGNSEESNRISITFFRL
  FRVMRLVKLLSRGEGIRTLLWTFIKSFQALPYVALLIAMLFFIYAVIGMQMFGKVAMRDN
  NQINRNNNFQTFPQAVLLLFRCATGEAWQEIMLACLPGKLCDPESDYNPGEEYTCGSNFA
  IVYFISFYMLCAFLIINLFVAVIMDNFDYLTRDWSILGPHHLDEFKRIWSEYDPEAKGRI
  KHLDVVTLLRRIQPPLGFGKLCPHRVACKRLVAMNMPLNSDGTVMFNATLFALVRTALKI
  KTEGNLEQANEELRAVIKKIWKKTSMKLLDQVVPPAGDDEVTVGKFYATFLIQDYFRKFK
  KRKEQGLVGKYPAKNTTIALQAGLRTLHDIGPEIRRAISCDLQDDEPEETKREEEDDVFK
  RNGALLGNHVNHVNSDRRDSLQQTNTTHRPLHVQRPSIPPASDTEKPLFPPAGNSVCHNH
  HNHNSIGKQVPTSTNANLNNANMSKAAHGKRPSIGNLEHVSENGHHSSHKHDREPQRRSS
  VKRTRYYETYIRSDSGDEQLPTICREDPEIHGYFRDPHCLGEQEYFSSEECYEDDSSPTW
  SRQNYGYYSRYPGRNIDSERPRGYHHPQGFLEDDDSPVCYDSRRSPRRRLLPPTPASHRR
  SSFNFECLRRQSSQEEVPSSPIFPHRTALPLHLMQQQIMAVAGLDSSKAQKYSPSHSTRS
  WATPPATPPYRDWTPCYTPLIQVEQSEALDQVNGSLPSLHRSSWYTDEPDISYRTFTPAS
  LTVPSSFRNKNSDKQRSADSLVEAVLISEGLGRYARDPKFVSATKHEIADACDLTIDEME
  SAASTLLNGNVRPRANGDVGPLSHRQDYELQDFGPGYSDEEPDPGRDEEDLADEMICITT
  L

• Sequence length: 2161