Free for academic non-profit institutions. Other users need a Commercial license

Aliases for CACNA1S Gene

Aliases for CACNA1S Gene

  • Calcium Voltage-Gated Channel Subunit Alpha1 S 2 3
  • Calcium Channel, Voltage-Dependent, L Type, Alpha 1S Subunit 2 3 5
  • Voltage-Gated Calcium Channel Subunit Alpha Cav1.1 3 4
  • CACNL1A3 3 4
  • 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
  • Dihydropyridine Receptor Alpha 1 Subunit 3
  • Dihydropyridine Receptor 3
  • CCHL1A3 3
  • Cav1.1 3
  • HOKPP1 3
  • HypoPP 3
  • CACH1 4
  • TTPP1 3
  • HOKPP 3
  • 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 Voltage-Gated Channel Subunit Alpha1 S) is a Protein Coding gene. Diseases associated with CACNA1S include hypokalemic periodic paralysis, type 1 and malignant hyperthermia susceptibility 5. Among its related pathways are Circadian entrainment and cAMP signaling pathway. GO annotations related to this gene include ion channel activity and high voltage-gated calcium channel activity. An important paralog of this gene is CACNA1A.

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 depolarization. They regulate intracellular processes such as contraction, secretion, neurotransmission and gene expression.

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

Promoters for CACNA1S Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around CACNA1S on UCSC Golden Path with GeneCards custom track

Genomic Location for CACNA1S Gene

Chromosome:
1
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

Genes around CACNA1S on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CACNA1S Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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 Asn 79, Asn 257, and Asn 1141
  • Modification sites at PhosphoSitePlus

Other Protein References for CACNA1S Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for CACNA1S Gene

Domains & Families for CACNA1S Gene

Gene Families for CACNA1S Gene

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 :
  • 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.
  • Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1S subfamily.
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.
genes like me logo Genes that share phenotypes with CACNA1S: view

Human Phenotype Ontology for CACNA1S Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CACNA1S Gene

MGI Knock Outs for CACNA1S:

Animal Model Products

miRNA for CACNA1S Gene

miRTarBase miRNAs that target CACNA1S

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Transcription Factor Targets 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 4
cytosol 1
extracellular 1

Gene Ontology (GO) - Cellular Components for CACNA1S Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 11206130
GO:0016020 membrane IEA --
GO:0031674 I band IDA 11206130
genes like me logo Genes that share ontologies with CACNA1S: view

Pathways & Interactions 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:0006816 calcium ion transport IDA 9852570
GO:0006936 muscle contraction IMP 17418573
GO:0007411 axon guidance TAS --
GO:0055085 transmembrane transport IEA --
GO:0070588 calcium ion transmembrane transport IEA --
genes like me logo Genes that share ontologies with CACNA1S: view

No data available for SIGNOR curated interactions for CACNA1S Gene

Drugs & Compounds for CACNA1S Gene

(36) Drugs for CACNA1S Gene - From: IUPHAR, DGIdb, DrugBank, HMDB, Novoseek, Tocris, and PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Nifedipine Approved Pharma Antagonist, Gating inhibitor, blocker, Target, inhibitor 106
Verapamil Approved Pharma Channel blocker, blocker, Target, inhibitor 117
Felodipine Approved, Investigational Pharma Potentiation, Activator, blocker, Target, inhibitor 22
Cinnarizine Approved Pharma Target, inhibitor 2
Ethanol Approved Pharma Target 1839

(7) Additional Compounds for CACNA1S Gene - From: Tocris, Novoseek, and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
O-Desmethylverapamil (D-702)
(+-)-Bay K 8644
71145-03-4
(S)-(-)-Bay K 8644
98625-26-4
Flunarizine dihydrochloride
30484-77-6
FPL 64176
120934-96-5

(5) Tocris Compounds for CACNA1S Gene

Compound Action Cas Number
(+-)-Bay K 8644 Ca2+ channel activator (L-type) 71145-03-4
(S)-(-)-Bay K 8644 Ca2+-channel activator (L-type) 98625-26-4
Flunarizine dihydrochloride Dual Na+/Ca2+ channel (T-type) blocker 30484-77-6
FPL 64176 Potent activator of Ca2+ channels (L-type) 120934-96-5
Nefiracetam Cognitive enhancer 77191-36-7
genes like me logo Genes that share compounds with CACNA1S: view

Transcripts for CACNA1S Gene

mRNA/cDNA for CACNA1S Gene

Unigene Clusters for CACNA1S Gene

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

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 (x50.7).

Protein differential expression in normal tissues from HIPED for CACNA1S Gene

This gene is overexpressed in Ovary (26.1), Frontal cortex (19.2), and Bone marrow stromal cell (13.3).

Integrated Proteomics: protein expression in normal tissues and cell lines 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 expression patterns with CACNA1S: view

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Protein tissue co-expression partners 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
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
chimpanzee
(Pan troglodytes)
Mammalia CACNA1S 35
  • 98.59 (n)
  • 98.56 (a)
CACNA1S 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Cacna1s 35
  • 88.39 (n)
  • 92.34 (a)
oppossum
(Monodelphis domestica)
Mammalia CACNA1S 36
  • 86 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CACNA1S 36
  • 79 (a)
OneToOne
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 37
  • 58 (a)
Ca-alpha1D 36
  • 40 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea egl-19 37
  • 61 (a)
unc-2 37
  • 44 (a)
egl-19 36
  • 53 (a)
OneToOne
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

Paralogs for CACNA1S Gene

(10) 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
rs12742169 - 201,083,182(+) GCCAG(A/T)GCGGC reference, missense
VAR_001499 Periodic paralysis hypokalemic 1 (HOKPP1)
rs1800559 Malignant hyperthermia 5 (MHS5) 201,060,815(-) ACAGC(A/G/T)CCAAT reference, missense
rs28930069 Periodic paralysis hypokalemic 1 (HOKPP1) 201,053,539(-) TGTTC(C/G)GTGTC reference, missense
rs28930068 Periodic paralysis hypokalemic 1 (HOKPP1) 201,053,538(-) GTTCC(A/G)TGTCA reference, missense

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

Variation tolerance for CACNA1S Gene

Residual Variation Intolerance Score: 61.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 17.17; 98.08% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CACNA1S Gene

HapMap Linkage Disequilibrium report
CACNA1S
Human Gene Mutation Database (HGMD)
CACNA1S

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

Disorders for CACNA1S Gene

MalaCards: The human disease database

(21) MalaCards diseases for CACNA1S Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hypokalemic periodic paralysis, type 1
  • familial periodic paralysis
malignant hyperthermia susceptibility 5
  • malignant hyperthermia susceptibility type 5
thyrotoxic periodic paralysis 1
  • thyrotoxic periodic paralysis, susceptibility to, 1
brugada syndrome 6
  • brgda6
periodic paralysis with transient compartment-like syndrome
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

CAC1S_HUMAN
  • 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.
  • 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.
  • 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.

Relevant External Links for CACNA1S

Genetic Association Database (GAD)
CACNA1S
Human Genome Epidemiology (HuGE) Navigator
CACNA1S
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CACNA1S
genes like me logo Genes that share disorders with CACNA1S: view

No data available for Genatlas for CACNA1S Gene

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 67
  2. Role of intraarterial therapy for cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage. (PMID: 20334460) Weant K.A. … Cook A.M. (Pharmacotherapy 2010) 25 26
  3. Nimodipine enhancement of alpha2 adrenergic modulation of NMDA receptor via a mechanism independent of Ca2+ channel blocking. (PMID: 20335610) Dong C.J. … Hare W.A. (Invest. Ophthalmol. Vis. Sci. 2010) 25 26
  4. L-type calcium channel blockers, morphine and pain: Newer insights. (PMID: 20661350) Kumar R. … Ray S.B. (Indian J Anaesth 2010) 25 26
  5. Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. (PMID: 19118277) Matthews E. … Hanna M.G. (Neurology 2009) 3 23

Products for CACNA1S Gene

Sources for CACNA1S Gene

Back to Top

Content