CACNA1S (calcium voltage-gated channel subunit alpha1 S)

Gene

• Entrez ID: 779
• Gene name: Calcium voltage-gated channel subunit alpha1 S
• Gene symbol: CACNA1S
• Synonyms: CACNL1A3, CCHL1A3, CMYO18, CMYP18, Cav1.1, DHPRM, HOKPP, HOKPP1, MHS5, TTPP1, hypoPP
• Chromosome: 1
• Chromosome location: 1q32.1
• Summary: This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and mal

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1325310	C>G,T	Benign, risk-factor	Intron variant
rs1800559	C>A,T	Drug-response, risk-factor	Coding sequence variant, missense variant
rs2281845	C>A,G,T	Benign, risk-factor	Upstream transcript variant
rs2297902	G>A,C	Benign, pathogenic	Missense variant, coding sequence variant, synonymous variant
rs28930068	C>T	Pathogenic	Coding sequence variant, missense variant
rs28930069	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs28986463	T>C	Risk-factor	Intron variant
rs80338777	C>A,T	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs80338778	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs80338779	C>A	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs116347156	C>G,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, coding sequence variant
rs139956524	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, coding sequence variant
rs141204958	G>A,T	Uncertain-significance, conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, stop gained, missense variant
rs145910245	T>A,G	Conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	Coding sequence variant, missense variant
rs146696298	C>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs148317787	C>T	Likely-pathogenic	Stop gained, coding sequence variant
rs201998231	G>A	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained
rs267606698	A>T	Pathogenic	Missense variant, coding sequence variant
rs530655602	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs563795648	G>A,T	Pathogenic	Coding sequence variant, missense variant, stop gained
rs762294904	G>A,T	Pathogenic	Stop gained, synonymous variant, coding sequence variant
rs763794604	C>A,T	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs764710968	C>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Intron variant
rs771706267	C>G,T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs772226819	G>A	Uncertain-significance, drug-response	Missense variant, coding sequence variant
rs797045031	T>C	Pathogenic	Splice acceptor variant
rs1553248947	T>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1553252746	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs1558056376	C>G,T	Likely-pathogenic, uncertain-significance	Splice donor variant
rs1558071742	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1558075630	C>T	Likely-pathogenic	Stop gained, coding sequence variant
rs1558079311	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1572023336	A>G	Likely-pathogenic	Splice donor variant
rs1572033599	C>T	Likely-pathogenic	Splice donor variant
rs1572035834	C>T	Pathogenic	Coding sequence variant, stop gained
rs1572036396	T>G	Likely-pathogenic	Splice acceptor variant
rs1572038993	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1572039465	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1572048220	C>T	Pathogenic	Coding sequence variant, stop gained
rs1572049461	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1572059904	G>C	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029696	hsa-miR-26b-5p	Microarray	19088304
MIRT2192292	hsa-miR-4650-5p	CLIP-seq
MIRT2385456	hsa-miR-1321	CLIP-seq
MIRT2385457	hsa-miR-4419a	CLIP-seq
MIRT2385458	hsa-miR-4510	CLIP-seq
MIRT2385459	hsa-miR-4728-5p	CLIP-seq
MIRT2385460	hsa-miR-4739	CLIP-seq
MIRT2385461	hsa-miR-4756-5p	CLIP-seq

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	9852570
GO:0005515	Function	Protein binding	IPI	25416956, 32296183
GO:0005516	Function	Calmodulin binding	IEA
GO:0005737	Component	Cytoplasm	IDA	11206130
GO:0005886	Component	Plasma membrane	IDA	11206130
GO:0005886	Component	Plasma membrane	TAS
GO:0005891	Component	Voltage-gated calcium channel complex	IDA	9852570
GO:0006816	Process	Calcium ion transport	IBA	21873635
GO:0006816	Process	Calcium ion transport	IDA	9852570
GO:0006936	Process	Muscle contraction	IMP	17418573
GO:0008331	Function	High voltage-gated calcium channel activity	IBA	21873635
GO:0008331	Function	High voltage-gated calcium channel activity	IDA	9852570
GO:0030315	Component	T-tubule	IDA	17204937
GO:0031674	Component	I band	IDA	11206130
GO:0034765	Process	Regulation of ion transmembrane transport	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0061337	Process	Cardiac conduction	TAS
GO:0070509	Process	Calcium ion import	IBA	21873635
GO:0070588	Process	Calcium ion transmembrane transport	IEA
GO:0071313	Process	Cellular response to caffeine	ISS
GO:1990454	Component	L-type voltage-gated calcium channel complex	ISS

Other IDs

• MIM: 114208
• HGNC: 1397
• e!Ensembl: ENSG00000081248

Protein

• UniProt ID: Q13698
• Protein name: Voltage-dependent L-type calcium channel subunit alpha-1S (Calcium channel, L type, alpha-1 polypeptide, isoform 3, skeletal muscle) (Voltage-gated calcium channel subunit alpha Cav1.1)
• Protein function: Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skel
• PDB: 2VAY, 6B27
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00520	Ion_trans	50 → 345	Ion transport protein	Family
  PF00520	Ion_trans	431 → 672	Ion transport protein	Family
  PF00520	Ion_trans	798 → 1076	Ion transport protein	Family
  PF00520	Ion_trans	1117 → 1392	Ion transport protein	Family
  PF16905	GPHH	1401 → 1454	Voltage-dependent L-type calcium channel, IQ-associated	Family
  PF08763	Ca_chan_IQ	1464 → 1538	Voltage gated calcium channel IQ domain	Domain

• Sequence:

  MEPSSPQDEGLRKKQPKKPVPEILPRPPRALFCLTLENPLRKACISIVEWKPFETIILLT
  IFANCVALAVYLPMPEDDNNSLNLGLEKLEYFFLIVFSIEAAMKIIAYGFLFHQDAYLRS
  GWNVLDFTIVFLGVFTVILEQVNVIQSHTAPMSSKGAGLDVKALRAFRVLRPLRLVSGVP
  SLQVVLNSIFKAMLPLFHIALLVLFMVIIYAIIGLELFKGKMHKTCYFIGTDIVATVENE
  EPSPCARTGSGRRCTINGSECRGGWPGPNHGITHFDNFGFSMLTVYQCITMEGWTDVLYW
  VNDAIGNEWPWIYFVTLILLGSFFILNLVLGVLSGEFTKEREKAKSRGTFQKLREKQQLD
  EDLRGYMSWITQGEVMDVEDFREGKLSLDEGGSDTESLYEIAGLNKIIQFIRHWRQWNRI
  FRWKCHDIVKSKVFYWLVILIVALNTLSIASEHHNQPLWLTRLQDIANRVLLSLFTTEML
  MKMYGLGLRQYFMSIFNRFDCFVVCSGILEILLVESGAMTPLGISVLRCIRLLRIFKITK
  YWTSLSNLVASLLNSIRSIASLLLLLFLFIVIFALLGMQLFGGRYDFEDTEVRRSNFDNF
  PQALISVFQVLTGEDWTSMMYNGIMAYGGPSYPGMLVCIYFIILFVCGNYILLNVFLAIA
  VDNLAEAESLTSAQKAKAEEKKRRKMSKGLPDKSEEEKSTMAKKLEQKPKGEGIPTTAKL
  KIDEFESNVNEVKDPYPSADFPGDDEEDEPEIPLSPRPRPLAELQLKEKAVPIPEASSFF
  IFSPTNKIRVLCHRIVNATWFTNFILLFILLSSAALAAEDPIRADSMRNQILKHFDIGFT
  SVFTVEIVLKMTTYGAFLHKGSFCRNYFNMLDLLVVAVSLISMGLESSAISVVKILRVLR
  VLRPLRAINRAKGLKHVVQCMFVAISTIGNIVLVTTLLQFMFACIGVQLFKGKFFRCTDL
  SKMTEEECRGYYYVYKDGDPMQIELRHREWVHSDFHFDNVLSAMMSLFTVSTFEGWPQLL
  YKAIDSNAEDVGPIYNNRVEMAIFFIIYIILIAFFMMNIFVGFVIVTFQEQGETEYKNCE
  LDKNQRQCVQYALKARPLRCYIPKNPYQYQVWYIVTSSYFEYLMFALIMLNTICLGMQHY
  NQSEQMNHISDILNVAFTIIFTLEMILKLMAFKARGYFGDPWNVFDFLIVIGSIIDVILS
  EIDTFLASSGGLYCLGGGCGNVDPDESARISSAFFRLFRVMRLIKLLSRAEGVRTLLWTF
  IKSFQALPYVALLIVMLFFIYAVIGMQMFGKIALVDGTQINRNNNFQTFPQAVLLLFRCA
  TGEAWQEILLACSYGKLCDPESDYAPGEEYTCGTNFAYYYFISFYMLCAFLVINLFVAVI
  MDNFDYLTRDWSILGPHHLDEFKAIWAEYDPEAKGRIKHLDVVTLLRRIQPPLGFGKFCP
  HRVACKRLVGMNMPLNSDGTVTFNATLFALVRTALKIKTEGNFEQANEELRAIIKKIWKR
  TSMKLLDQVIPPIGDDEVTVGKFYATFLIQEHFRKFMKRQEEYYGYRPKKDIVQIQAGLR
  TIEEEAAPEICRTVSGDLAAEEELERAMVEAAMEEGIFRRTGGLFGQVDNFLERTNSLPP
  VMANQRPLQFAEIEMEEMESPVFLEDFPQDPRTNPLARANTNNANANVAYGNSNHSNSHV
  FSSVHYEREFPEETETPATRGRALGQPCRVLGPHSKPCVEMLKGLLTQRAMPRGQAPPAP
  CQCPRVESSMPEDRKSSTPGSLHEETPHSRSTRENTSRCSAPATALLIQKALVRGGLGTL
  AADANFIMATGQALADACQMEPEEVEIMATELLKGREAPEGMASSLGCLNLGSSLGSLDQ
  HQGSQETLIPPRL

• Sequence length: 1873

Pathways

KEGG:

MAPK signaling pathway
Calcium signaling pathway
cGMP-PKG signaling pathway
cAMP signaling pathway
Cardiac muscle contraction
Adrenergic signaling in cardiomyocytes
Vascular smooth muscle contraction
Retrograde endocannabinoid signaling
Cholinergic synapse
Serotonergic synapse
GABAergic synapse
Insulin secretion
GnRH signaling pathway
Oxytocin signaling pathway
Renin secretion
Aldosterone synthesis and secretion
Cortisol synthesis and secretion
GnRH secretion
Cushing syndrome
Growth hormone synthesis, secretion and action
Alzheimer disease
Prion disease
Pathways of neurodegeneration - multiple diseases
Chemical carcinogenesis - receptor activation
Hypertrophic cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
Dilated cardiomyopathy

Reactome:

Phase 0 - rapid depolarisation
Phase 2 - plateau phase

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Adrenocortical adenoma	Adrenal Cortical Adenoma	rs121913035
Atrioventricular block	Second degree atrioventricular block	rs766840243, rs763809932
Congenital myopathy	Congenital myopathy (disorder)	rs80358247, rs199474720, rs80358248, rs121964852, rs199474719, rs121964853, rs121964854, rs104894129, rs137853306, rs199476153, rs199476147, rs137853307, rs28930068, rs121909519, rs121909521, rs121909522, rs121909523, rs121909524, rs121909529, rs121909531, rs137852801, rs387907072, rs387907073, rs387907196, rs367543049, rs398122936, rs199476146, rs606231257, rs797045950, rs768144106, rs564856283, rs876661406, rs876661407, rs886041584, rs769114543, rs1064794287, rs759242559, rs780703403, rs1421405659, rs1235665641, rs1563929454, rs1179926739, rs1565943228, rs1571893814, rs1567819905, rs1593846841, rs752326328, rs1570098248, rs1176071790, rs1392068839, rs1572148902, rs1572148914, rs1553251644, rs1571456678, rs1558081664, rs147517396, rs1577005361, rs80338778	28012042
Hyperthyroidism	Hyperthyroidism	rs121908861, rs121908864, rs121908874, rs121908875, rs121908876, rs121908877, rs121908873, rs121908880, rs121908883, rs121909258, rs6256, rs869312167
Hypokalemic periodic paralysis	Hypokalemic periodic paralysis, Hypokalemic periodic paralysis type 1	rs80338957, rs121908544, rs121908548, rs80338784, rs80338788, rs80338785, rs121908555, rs121908557, rs28930068, rs28930069, rs80338777, rs267606698, rs80338778, rs80338789, rs527236148, rs527236150, rs367983954, rs1558056376, rs148317787, rs1287079817, rs1572049461, rs1572023336, rs1287863349	19822448, 11912116, 29572832, 19225109, 17418573, 11555352, 28857175, 18835861, 9066893, 11808349, 8605978, 19118277, 21841462, 18229654, 23187123, 10639629, 18162704, 7847370, 7987325, 8004673, 15716625, 11034874, 15726306, 9852570, 9512357, 26633545, 25213595
Liver failure	Liver Failure, Acute	rs118203990, rs118203991, rs118203992, rs387907022, rs201861847, rs796065037, rs759315662, rs368196005, rs796052121, rs369437593, rs367683258, rs766314948, rs368085185, rs770446752, rs753039116, rs776797592, rs1490906786, rs1562849964, rs759960319, rs776597537, rs375350359, rs1573008071, rs1601977105, rs1174791046, rs1019313682
Obesity	Obesity	rs34911341, rs74315349, rs1474810899, rs2282440, rs2491132, rs121918111, rs796065034, rs753856820, rs796065035, rs121918112, rs104894023, rs137852821, rs1580764441, rs137852822, rs137852823, rs137852824, rs13447324, rs121913562, rs121913564, rs74315393, rs121913556, rs2989924, rs193922650, rs193922685, rs193922687, rs751160202, rs1421085, rs747681609, rs1553400259, rs13447339, rs370479598, rs1554394014, rs1553174844, rs756232889, rs369841551, rs1557670950, rs1571321748, rs148538980, rs1572820988, rs1591461970, rs1419374563, rs745921568, rs144159890, rs1570714352, rs779783209, rs1573250294, rs1573254045, rs1580744791, rs1580746829, rs6548238, rs7138803, rs7754840
Oligodontia	Oligodontia	rs1591901585	29364747
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	21926974
Thyrotoxic periodic paralysis	Thyrotoxic periodic paralysis	rs527236153, rs527236158, rs672601244, rs527236159, rs28986463	15001631
Tooth agenesis	Tooth Agenesis, Selective, With Orofacial Cleft, Tooth Agenesis, Familial, TOOTH AGENESIS, SELECTIVE, 9	rs121908119, rs121908121, rs1881345182, rs104894467, rs28933970, rs2139108031, rs28933971, rs28933972, rs1594475481, rs2139106532, rs2139108874, rs121917720, rs121913129, rs104893852, rs104893850, rs121913130, rs1553877821, rs782540538, rs318240759, rs515726227, rs587776350, rs864309647, rs864309649, rs869320640, rs869320636, rs866789963, rs869320639, rs869320637, rs779326570, rs766021478, rs372993798, rs1057519288, rs1555316697, rs1131692057, rs1565611848, rs745522921, rs773036759	29364747
Ventricular fibrillation	Ventricular Fibrillation	rs137854604, rs587782933, rs190140598
Ventricular tachycardia	Tachycardia, Ventricular	rs137853228, rs397517025, rs199473373, rs727504432, rs1450434935, rs1592847299

Unknown
Disease name	Disease term	dbSNP ID	References
Anodontia	Developmental absence of tooth		29364747
Blood coagulation disorders	Blood Coagulation Disorders
Congestive heart failure	High-output congestive heart failure	rs2301610, rs3833910, rs12301951, rs201674674, rs186741807, rs150140412, rs786205727, rs757840030, rs552050895, rs759465783, rs201978086, rs572757800, rs1572143354, rs749160569
Graves disease	Graves Disease
Hyperphosphatemia	Hyperphosphatemia (disorder)
Hypodontia	Hypodontia		29364747
Hypodontia oligodontia with orofacial cleft	Hypodontia Oligodontia with Orofacial Cleft		29364747
Necrotizing myopathy	Necrotizing myopathy
Periodic hypokalemic paresis	Periodic hypokalemic paresis
Periodic paralysis	Familial Periodic Paralysis, periodic paralysis (finding)
Periodic paralysis with transient compartment-like syndrome	Periodic paralysis with transient compartment-like syndrome		24240197
Quadriplegia	Quadriplegia
Respiratory failure	Respiratory Failure		19822448
Supraventricular tachycardia	Supraventricular tachycardia
Thyrotoxicosis with toxic single thyroid nodule	Thyrotoxicosis with toxic single thyroid nodule
Tooth development and eruption disorder	Tooth development and eruption disorder		29364747
Toxic goiter	Toxic multinodular goiter