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 (NCBI Gene): 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 c

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
MIRT441027	hsa-miR-136-5p	HITS-CLIP	24374217
MIRT857554	hsa-miR-134	CLIP-seq
MIRT857555	hsa-miR-190	CLIP-seq
MIRT857556	hsa-miR-190b	CLIP-seq
MIRT857557	hsa-miR-3118	CLIP-seq
MIRT857558	hsa-miR-3136-5p	CLIP-seq
MIRT857559	hsa-miR-3146	CLIP-seq
MIRT857560	hsa-miR-4434	CLIP-seq
MIRT857561	hsa-miR-4439	CLIP-seq
MIRT857562	hsa-miR-4513	CLIP-seq
MIRT857563	hsa-miR-4516	CLIP-seq
MIRT857564	hsa-miR-4771	CLIP-seq
MIRT857565	hsa-miR-4802-3p	CLIP-seq
MIRT1954679	hsa-let-7a	CLIP-seq
MIRT1954680	hsa-let-7b	CLIP-seq
MIRT1954681	hsa-let-7c	CLIP-seq
MIRT1954682	hsa-let-7d	CLIP-seq
MIRT1954683	hsa-let-7e	CLIP-seq
MIRT1954684	hsa-let-7f	CLIP-seq
MIRT1954685	hsa-let-7g	CLIP-seq
MIRT1954686	hsa-let-7i	CLIP-seq
MIRT1954687	hsa-miR-202	CLIP-seq
MIRT1954688	hsa-miR-371b-3p	CLIP-seq
MIRT1954689	hsa-miR-4458	CLIP-seq
MIRT1954690	hsa-miR-4500	CLIP-seq
MIRT1954691	hsa-miR-607	CLIP-seq
MIRT1954692	hsa-miR-98	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005216	Function	Monoatomic ion channel activity	IEA
GO:0005245	Function	Voltage-gated calcium channel activity	IDA	11160515, 18482979, 21131953
GO:0005245	Function	Voltage-gated calcium channel activity	IEA
GO:0005245	Function	Voltage-gated calcium channel activity	IMP	23913001
GO:0005262	Function	Calcium channel activity	IEA
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	IBA
GO:0005891	Component	Voltage-gated calcium channel complex	IDA	11160515
GO:0005891	Component	Voltage-gated calcium channel complex	IEA
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006816	Process	Calcium ion transport	IDA	11160515
GO:0006816	Process	Calcium ion transport	IEA
GO:0006936	Process	Muscle contraction	IEA
GO:0007154	Process	Cell communication	IEA
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	ISS
GO:0007605	Process	Sensory perception of sound	IMP	21131953
GO:0008092	Function	Cytoskeletal protein binding	IEA
GO:0008331	Function	High voltage-gated calcium channel activity	IDA	1309651
GO:0010959	Process	Regulation of metal ion transport	IEA
GO:0016020	Component	Membrane	IEA
GO:0023052	Process	Signaling	IEA
GO:0030018	Component	Z disc	ISS
GO:0030315	Component	T-tubule	IEA
GO:0030506	Function	Ankyrin binding	ISS	21859974
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0034702	Component	Monoatomic ion channel complex	IEA
GO:0045762	Process	Positive regulation of adenylate cyclase activity	ISS
GO:0046872	Function	Metal ion binding	IEA
GO:0050877	Process	Nervous system process	IEA
GO:0051050	Process	Positive regulation of transport	IEA
GO:0051393	Function	Alpha-actinin binding	IPI	17110593
GO:0051928	Process	Positive regulation of calcium ion transport	IDA	1309651
GO:0055085	Process	Transmembrane transport	IEA
GO:0060372	Process	Regulation of atrial cardiac muscle cell membrane repolarization	ISS
GO:0070509	Process	Calcium ion import	IDA	1309651
GO:0070588	Process	Calcium ion transmembrane transport	IEA
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:0086007	Function	Voltage-gated calcium channel activity involved in cardiac muscle cell action potential	IEA
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:0098703	Process	Calcium ion import across plasma membrane	IBA
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 expressio
• PDB: 3LV3, 7UHF, 7UHG, 8E59, 8E5A, 8E5B
• 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

• Tissue specificity: TISSUE SPECIFICITY: Expressed in pancreatic islets and in brain, where it has been seen in cerebral cortex, hippocampus, basal ganglia, habenula and thalamus. Expressed in the small cell lung carcinoma cell line SCC-9. No expression in skeletal muscle. {E
• 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

Pathways

KEGG:

MAPK signaling pathway
Calcium signaling pathway
cGMP-PKG signaling pathway
cAMP signaling pathway
Cellular senescence
Cardiac muscle contraction
Adrenergic signaling in cardiomyocytes
Vascular smooth muscle contraction
Tight junction
Circadian entrainment
Retrograde endocannabinoid signaling
Glutamatergic synapse
Cholinergic synapse
Serotonergic synapse
GABAergic synapse
Dopaminergic synapse
Insulin secretion
GnRH signaling pathway
Oxytocin signaling pathway
Renin secretion
Aldosterone synthesis and secretion
Cortisol synthesis and secretion
GnRH secretion
Type II diabetes mellitus
Cushing syndrome
Growth hormone synthesis, secretion and action
Carbohydrate digestion and absorption
Alzheimer disease
Prion disease
Pathways of neurodegeneration - multiple diseases
Amphetamine addiction
Chemical carcinogenesis - receptor activation
Hypertrophic cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
Dilated cardiomyopathy

Reactome:

Regulation of insulin secretion
Phase 0 - rapid depolarisation
Phase 2 - plateau phase

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Associated diseases

Causal
Disease merge term	Disease name	dbSNP ID	References
Sinoatrial Node Dysfunction And Deafness	sinoatrial node dysfunction and deafness	rs398122827, rs1576484361	N/A

Unknown
Disease merge term	Disease name	Evidence	References	Source
Adenoma	aldosterone-producing adenoma with seizures and neurological abnormalities	N/A	N/A	GenCC
hearing impairment	Hearing impairment	N/A	N/A	ClinVar
Heart Failure	Heart failure	N/A	N/A	GWAS
Hypertension	Hypertension (PheCode 401), Hypertension, Resistant hypertension, Hypertension (confirmatory factor analysis Factor 12), Essential hypertension (PheCode 401.1), High blood pressure / hypertension	N/A	N/A	GWAS
Insomnia	Insomnia	N/A	N/A	GWAS
Mental retardation	intellectual disability	N/A	N/A	ClinVar
Metabolic Syndrome	Metabolic syndrome	N/A	N/A	GWAS
Schizophrenia	Schizophrenia	N/A	N/A	GWAS

Associations from Text Mining
Disease Name	Relationship Type	References
ACTH Secreting Pituitary Adenoma	Associate	26743443
Adenocarcinoma Clear Cell	Associate	37697729
Adenocarcinoma of Lung	Associate	34111567
Adenoma	Associate	24866132
Adrenal Hyperplasia Congenital	Associate	34232123
Adrenocortical Adenoma	Associate	26765578, 31789380
Arrhythmias Cardiac	Associate	39551029
Attention Deficit Disorder with Hyperactivity	Associate	36430690
Autism Spectrum Disorder	Associate	25620733, 28472301, 30465465, 31838722, 31921405, 35220405, 35453044, 38553610
Autistic Disorder	Associate	25620733, 28472301, 31921405, 36430690
Bipolar Disorder	Associate	25730879
Carcinogenesis	Associate	34111567
Cardiac Conduction System Disease	Associate	39551029
Cerebral Palsy	Associate	40243517
Channelopathies	Associate	35453044, 36208199
Colorectal Neoplasms	Associate	29079724
Congenital Hyperinsulinism	Associate	32336187, 35453044
Cushing Syndrome	Associate	26743443
Deafness	Associate	36430690
Developmental Disabilities	Associate	30054272, 30465465, 31921405, 35453044, 36208199
Diabetes Mellitus	Associate	39273144
Diabetes Mellitus Type 1	Associate	30543678
Diabetes Mellitus Type 2	Associate	39273144
Down Syndrome	Associate	27293319
Dyslipidemias	Associate	30365130
Endocrine System Diseases	Associate	31921405, 36208199, 38553610
Endometriosis	Associate	31909458
Epilepsies Partial	Associate	36430690
Epilepsy	Associate	28472301, 30054272, 36430690
Epilepsy Idiopathic Generalized	Associate	36430690
Familial Hyperaldosteronism	Associate	27729216, 37846579
Genetic Diseases Inborn	Associate	34232123
Hearing Loss	Associate	30054272
Hearing Loss Unilateral	Associate	40302475
Heart Defects Congenital	Associate	28318089
Herpes Zoster	Associate	27098837
Hyperaldosteronism	Associate	23913001, 24866132, 25253161, 25906099, 25958045, 26252618, 26351028, 26743443, 26807823, 27098837, 27729216, 30085035, 30354720, 30465465, 30739536, 31000732, 31484828, 32336187, 32516371, 33677921, 33796077, 34232123, 36430690, 37846579, 40302475
Hyperplasia	Associate	26252618, 28388725
Hypertension	Associate	19225208, 34593835, 37846579
Hypoglycemia	Associate	36208199
Hypothalamic hamartomas	Associate	18076645
Inflammation	Associate	26990456
Intellectual Disability	Associate	25620733, 28472301, 32336187, 36430690
Leukemia Myelogenous Chronic BCR ABL Positive	Associate	23651669
Lymphedema	Associate	28318089
Lymphoma Large B Cell Diffuse	Associate	27835906
Mental Disorders	Associate	35220405
Muscle Hypotonia	Associate	28318089, 32336187
Myopia	Associate	27611182
Neoplasms	Associate	22904677, 26404961, 27196083, 27716384, 31000732, 37697729
Neurodegenerative Diseases	Associate	25173401, 40244042
Neurologic Manifestations	Associate	25620733, 28472301, 38553610
Neuromuscular Diseases	Associate	28318089
Parkinson Disease	Stimulate	25173401
Parkinson Disease	Associate	31199560, 36350063, 40244042
Prostatic Neoplasms	Associate	26404961, 26990456
Prostatic Neoplasms	Stimulate	36949059
Prostatic Neoplasms Castration Resistant	Associate	26990456
Schizophrenia	Associate	35220405
Seizures	Associate	25620733, 28472301
Sick Sinus Syndrome	Associate	36430690
Sick Sinus Syndrome 2 Autosomal Dominant	Associate	36430690
Signs and Symptoms	Associate	32336187
Sinoatrial Block	Associate	30498240, 39551029
Stomach Neoplasms	Associate	36484990
Tachycardia Ventricular	Associate	39551029
Tuberous Sclerosis	Associate	34417327
Vascular Malformations	Associate	27716384