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Aliases for CACNA1S Gene

Aliases for CACNA1S Gene

  • Calcium Channel, Voltage-Dependent, L Type, Alpha 1S Subunit 2 3
  • CACNL1A3 3 4 6
  • Voltage-Gated Calcium Channel Subunit Alpha Cav1.1 3 4
  • CCHL1A3 3 6
  • HOKPP1 3 6
  • TTPP1 3 6
  • Calcium Channel, L Type, Alpha 1 Polypeptide, Isoform 3 (Skeletal Muscle, Hypokalemic Periodic Paralysis) 3
  • Calcium Channel, L Type, Alpha-1 Polypeptide, Isoform 3, Skeletal Muscle 4
  • Dihydropyridine-Sensitive L-Type Calcium Channel Alpha-1 Subunit 3
  • Voltage-Dependent L-Type Calcium Channel Subunit Alpha-1S 3
  • Dihydropyridine Receptor 3
  • Cav1.1 3
  • HypoPP 3
  • HOKPP 3
  • CACH1 4
  • CACN1 4
  • MHS5 3

External Ids for CACNA1S Gene

Previous HGNC Symbols for CACNA1S Gene

  • HOKPP
  • MHS5
  • CACNL1A3

Previous GeneCards Identifiers for CACNA1S Gene

  • GC01M198738
  • GC01M196467
  • GC01M197475
  • GC01M198296
  • GC01M197740
  • GC01M199275
  • GC01M172185

Summaries for CACNA1S Gene

Entrez Gene Summary for CACNA1S Gene

  • 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 malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]

GeneCards Summary for CACNA1S Gene

CACNA1S (Calcium Channel, Voltage-Dependent, L Type, Alpha 1S Subunit) is a Protein Coding gene. Diseases associated with CACNA1S include hypokalemic periodic paralysis, type 1 and thyrotoxic periodic paralysis 1. Among its related pathways are MAPK signaling pathway and L1CAM interactions. GO annotations related to this gene include voltage-gated calcium channel activity and high voltage-gated calcium channel activity. An important paralog of this gene is CACNA1D.

UniProtKB/Swiss-Prot for CACNA1S Gene

  • 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-1S 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-1S subunit play an important role in excitation-contraction coupling in skeletal muscle

Tocris Summary for CACNA1S Gene

  • Voltage-gated calcium channels (CaV) are present in the membrane of most excitable cells and mediate calcium influx in response to depolarisation. They regulate intracellular processes such as contraction, secretion, neurotransmission and gene expression. Voltage-gated calcium channels are formed from four or five distinct subunits; the alpha-subunit is the largest subunit and incorporates the voltage sensor, conduction pore and gating apparatus. Using pharmacological and electrophysiological techniques, at least 6 types of voltage-gated channels have been identified: L, N, P, Q, R and T, which are grouped into three families. Cav1.x are high-voltage-activated dihydropyridine-sensitive (L-type), Cav2.x are high-voltage-activated dihydropyridine-insensitive (N-, P- Q- and R-types) and Cav3.x are low-voltage-activated channels (T-type).

Gene Wiki entry for CACNA1S Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CACNA1S Gene

Genomics for CACNA1S Gene

Regulatory Elements for CACNA1S Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for CACNA1S Gene

Start:
201,039,507 bp from pter
End:
201,112,566 bp from pter
Size:
73,060 bases
Orientation:
Minus strand

Genomic View for CACNA1S Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for CACNA1S Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CACNA1S Gene

Proteins for CACNA1S Gene

  • Protein details for CACNA1S Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13698-CAC1S_HUMAN
    Recommended name:
    Voltage-dependent L-type calcium channel subunit alpha-1S
    Protein Accession:
    Q13698
    Secondary Accessions:
    • A4IF51
    • B1ALM2
    • Q12896
    • Q13934

    Protein attributes for CACNA1S Gene

    Size:
    1873 amino acids
    Molecular mass:
    212350 Da
    Quaternary structure:
    • Multisubunit complex 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. An additional gamma subunit is present only in skeletal muscle L-type channel. Interacts with DYSF and JSRP1. Interacts with RYR1 (By similarity).

    Three dimensional structures from OCA and Proteopedia for CACNA1S Gene

neXtProt entry for CACNA1S Gene

Proteomics data for CACNA1S Gene at MOPED

Post-translational modifications for CACNA1S Gene

  • Phosphorylation by PKA activates the calcium channel.
  • Glycosylation at Asn79, Asn257, and Asn1141
  • Modification sites at PhosphoSitePlus

Other Protein References for CACNA1S Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for CACNA1S Gene

Domains for CACNA1S Gene

Gene Families for CACNA1S Gene

HGNC:
  • CACN :Calcium channel subunits
  • CACN1 :Voltage-gated ion channels / Calcium channels
IUPHAR :

Suggested Antigen Peptide Sequences for CACNA1S Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q13698

UniProtKB/Swiss-Prot:

CAC1S_HUMAN :
  • Q13698
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
  • The loop between repeats II and III interacts with the ryanodine receptor, and is therefore important for calcium release from the endoplasmic reticulum necessary for muscle contraction
Family:
  • Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1S subfamily.
genes like me logo Genes that share domains with CACNA1S: view

Function for CACNA1S Gene

Molecular function for CACNA1S Gene

GENATLAS Biochemistry: transverse tubule (TT) calcium voltage-gated channel (VDCC),L (long lasting) type,alpha 1S subunit,expressed in skeletal muscle,dihydropyridine (DHP) sensitive,isoform 3,involved in excitation-contraction coupling,ortholog of the mdg (muscular dysgenesis murine gene)
UniProtKB/Swiss-Prot 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-1S 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-1S subunit play an important role in excitation-contraction coupling in skeletal muscle

Gene Ontology (GO) - Molecular Function for CACNA1S Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005216 ion channel activity --
GO:0005245 voltage-gated calcium channel activity IDA 9852570
GO:0005515 protein binding IPI 25416956
GO:0008331 high voltage-gated calcium channel activity IDA 9852570
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with CACNA1S: view
genes like me logo Genes that share phenotypes with CACNA1S: view

miRNA for CACNA1S Gene

miRTarBase miRNAs that target CACNA1S

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for CACNA1S

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targeting and HOMER Transcription for CACNA1S Gene

Localization for CACNA1S Gene

Subcellular locations from UniProtKB/Swiss-Prot for CACNA1S Gene

Membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for CACNA1S Gene COMPARTMENTS Subcellular localization image for CACNA1S gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 3
extracellular 1

Gene Ontology (GO) - Cellular Components for CACNA1S Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 11206130
GO:0005886 plasma membrane IDA 11206130
GO:0005891 voltage-gated calcium channel complex IDA 9852570
GO:0016020 membrane --
GO:0016529 sarcoplasmic reticulum IEA --
genes like me logo Genes that share ontologies with CACNA1S: view

Pathways for CACNA1S Gene

genes like me logo Genes that share pathways with CACNA1S: view

Gene Ontology (GO) - Biological Process for CACNA1S Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001501 skeletal system development IEA --
GO:0002074 extraocular skeletal muscle development IEA --
GO:0006811 ion transport --
GO:0006816 calcium ion transport IDA 9852570
GO:0006936 muscle contraction IMP 17418573
genes like me logo Genes that share ontologies with CACNA1S: view

Compounds for CACNA1S Gene

(5) Tocris Compounds for CACNA1S Gene

Compound Action Cas Number
Isradipine Ca2+ channel blocker (L-type) [75695-93-1]
Mibefradil dihydrochloride Ca2+ channel blocker (T-type) [116666-63-8]
omega-Conotoxin GVIA Ca2+ channel blocker (N-type) [106375-28-4]
Pregabalin Anticonvulsant; selectively binds the alpha2delta subunit of voltage-sensitive calcium channels [148553-50-8]
SNX 482 Potent and selective CaV2.3 blocker (R-type) [203460-30-4]

(2) HMDB Compounds for CACNA1S Gene

Compound Synonyms Cas Number PubMed IDs
Calcium
  • Ca
7440-70-2
Verapamil
  • Akilen
52-53-9

(14) Drugbank Compounds for CACNA1S Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Amlodipine
  • Amlodipine Benzenesulfonate
88150-42-9 target inhibitor
Cinnarizine
298-57-7 target inhibitor
Clevidipine
166432-28-6 target
Dronedarone
141626-36-0 target
Felodipine
  • Dl-Felodipine
72509-76-3 target inhibitor

(8) IUPHAR Ligand for CACNA1S Gene

Ligand Type Action Affinity Pubmed IDs
[3H](+)-isradipine Gating inhibitor None 11
diltiazem Channel blocker None
SZ(+)-(S)-202-791 Activator None
calciseptine Channel blocker None
FPL64176 Activator None
(-)-(S)-BayK8644 Activator None
nifedipine Activator None
verapamil Inhibitor Inhibition

(6) Novoseek inferred chemical compound relationships for CACNA1S Gene

Compound -log(P) Hits PubMed IDs
dihydropyridine 78.1 10
ryanodine 63.4 1
calcium 61.5 37
sodium 40.4 3
histidine 38.1 2

(1) PharmGKB related drug/compound annotations for CACNA1S Gene

Drug/compound Annotation
succinylcholine
genes like me logo Genes that share compounds with CACNA1S: view

Transcripts for CACNA1S Gene

mRNA/cDNA for CACNA1S Gene

(28) Selected AceView cDNA sequences:
(5) Additional mRNA sequences :
(2) REFSEQ mRNAs :
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for CACNA1S Gene

Calcium channel, voltage-dependent, L type, alpha 1S subunit:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for CACNA1S

Primer Products

  • OriGene qSTAR qPCR primer pairs in human,mouse,rat for CACNA1S
  • QuantiTect SYBR Green Assays in human,mouse,rat
  • Pre-validated RT² qPCR Primer Assay in human,mouse,rat
  • QuantiFast Probe-based Assays in human,mouse,rat

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for CACNA1S Gene

No ASD Table

Relevant External Links for CACNA1S Gene

GeneLoc Exon Structure for
CACNA1S
ECgene alternative splicing isoforms for
CACNA1S

Expression for CACNA1S Gene

mRNA expression in normal human tissues for CACNA1S Gene

mRNA differential expression in normal tissues according to GTEx for CACNA1S Gene

This gene is overexpressed in Muscle - Skeletal (50.7).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for CACNA1S Gene

SOURCE GeneReport for Unigene cluster for CACNA1S Gene Hs.1294

mRNA Expression by UniProt/SwissProt for CACNA1S Gene

Q13698-CAC1S_HUMAN
Tissue specificity: Skeletal muscle specific
genes like me logo Genes that share expressions with CACNA1S: view

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for CACNA1S Gene

Orthologs for CACNA1S Gene

This gene was present in the common ancestor of animals.

Orthologs for CACNA1S Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CACNA1S 35
  • 98.59 (n)
  • 98.56 (a)
CACNA1S 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia CACNA1S 35
  • 83.93 (n)
  • 85.55 (a)
CACNA1S 36
  • 86 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CACNA1S 35
  • 90.51 (n)
  • 93.06 (a)
CACNA1S 36
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Cacna1s 35
  • 88.2 (n)
  • 92.45 (a)
Cacna1s 16
Cacna1s 36
  • 92 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CACNA1S 36
  • 86 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CACNA1S 36
  • 79 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Cacna1s 35
  • 88.39 (n)
  • 92.34 (a)
chicken
(Gallus gallus)
Aves CACNA1S 35
  • 78.16 (n)
  • 81.43 (a)
CACNA1S 36
  • 79 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CACNA1S 36
  • 77 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.11094 35
zebrafish
(Danio rerio)
Actinopterygii cacna1sa 35
  • 71.93 (n)
  • 74.71 (a)
cacna1sa 36
  • 71 (a)
OneToMany
cacna1sb 36
  • 68 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Ca-alpha1D 36
  • 40 (a)
OneToOne
Ca-alpha1D 37
  • 58 (a)
worm
(Caenorhabditis elegans)
Secernentea egl-19 36
  • 53 (a)
OneToOne
unc-2 37
  • 44 (a)
egl-19 37
  • 61 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 21 (a)
ManyToMany
Species with no ortholog for CACNA1S:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for CACNA1S Gene

ENSEMBL:
Gene Tree for CACNA1S (if available)
TreeFam:
Gene Tree for CACNA1S (if available)

Paralogs for CACNA1S Gene

Selected SIMAP similar genes for CACNA1S Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with CACNA1S: view

Variants for CACNA1S Gene

Sequence variations from dbSNP and Humsavar for CACNA1S Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs734879 -- 201,080,779(-) AAGAT(C/G)AGATC intron-variant
rs734880 -- 201,081,164(-) CCTGG(A/G)CCTGC intron-variant
rs734881 -- 201,081,156(-) TGCAT(A/G)AGGTG intron-variant
rs745835 -- 201,112,275(-) TCCTG(A/T)GATTC reference, missense
rs877444 -- 201,098,823(+) CCTCA(C/G)CCCCC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for CACNA1S Gene

Variant ID Type Subtype PubMed ID
nsv4054 CNV Insertion 18451855
esv1000350 CNV Deletion 20482838
nsv428301 CNV Gain 18775914
nsv515571 CNV Loss 19592680

Relevant External Links for CACNA1S Gene

HapMap Linkage Disequilibrium report
CACNA1S
Human Gene Mutation Database (HGMD)
CACNA1S
Locus Specific Mutation Databases (LSDB)
CACNA1S

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CACNA1S Gene

Disorders for CACNA1S Gene

(3) OMIM Diseases for CACNA1S Gene (114208)

UniProtKB/Swiss-Prot

CAC1S_HUMAN
  • Periodic paralysis hypokalemic 1 (HOKPP1) [MIM:170400]: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. {ECO:0000269 PubMed:17418573, ECO:0000269 PubMed:18162704, ECO:0000269 PubMed:19118277, ECO:0000269 PubMed:7987325, ECO:0000269 PubMed:8004673}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Malignant hyperthermia 5 (MHS5) [MIM:601887]: Autosomal dominant disorder that is potentially lethal in susceptible individuals on exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants. {ECO:0000269 PubMed:9199552}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • Thyrotoxic periodic paralysis 1 (TTPP1) [MIM:188580]: A sporadic muscular disorder characterized by episodic weakness and hypokalemia during a thyrotoxic state. It is clinically similar to hereditary hypokalemic periodic paralysis, except for the fact that hyperthyroidism is an absolute requirement for disease manifestation. The disease presents with recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest. Thyrotoxic periodic paralysis can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves disease. {ECO:0000269 PubMed:15001631}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

(3) University of Copenhagen DISEASES for CACNA1S Gene

(5) Novoseek inferred disease relationships for CACNA1S Gene

Disease -log(P) Hits PubMed IDs
hypokalemic periodic paralysis 97.5 20
periodic paralysis 92.1 6
central core disease 79 1
hypokalemia 56.2 1
paralysis 52.4 1

Relevant External Links for CACNA1S

GeneTests
CACNA1S
GeneReviews
CACNA1S
Genetic Association Database (GAD)
CACNA1S
Human Genome Epidemiology (HuGE) Navigator
CACNA1S
genes like me logo Genes that share disorders with CACNA1S: view

Publications for CACNA1S Gene

  1. Assignment of the human gene for the alpha-1 subunit of the skeletal muscle DHP-sensitive calcium channel (CACNL1A3) to chromosome 1q31- q32. (PMID: 7916735) Gregg R.G. … Powers P.A. (Genomics 1993) 2 3 4 23
  2. Cloning of the human skeletal muscle alpha 1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3). (PMID: 7713519) Hogan K. … Gregg R.G. (Genomics 1994) 3 4 23
  3. Malignant-hyperthermia susceptibility is associated with a mutation of the alpha-1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle. (PMID: 9199552) Monnier N. … Lunardi J. (Am. J. Hum. Genet. 1997) 3 4 23
  4. Skeletal muscle dihydropyridine-sensitive calcium channel (CACNA1S) gene mutations in chinese patients with hypokalemic periodic paralysis. (PMID: 15711422) Lin S.H. … Kao M.C. (Am. J. Med. Sci. 2005) 3 23 48
  5. The structure of the gene encoding the human skeletal muscle alpha 1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3). (PMID: 8838325) Hogan K. … Powers P.A. (Genomics 1996) 3 4 23

Products for CACNA1S Gene

  • antibodies-online proteins for CACNA1S
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Sources for CACNA1S Gene

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