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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

CACNA1S Gene

protein-coding   GIFtS: 70
GCID: GC01M201008

Calcium Channel, Voltage-Dependent, L Type, Alpha 1S Subunit


(Previous symbols: HOKPP, MHS5, CACNL1A3)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Calcium Channel, Voltage-Dependent, L Type, Alpha 1S Subunit1 2     Calcium Channel, L Type, Alpha 1 Polypeptide, Isoform 3 (Skeletal Muscle,
Hypokalemic Periodic Paralysis)2
CACNL1A31 2 3 5     Dihydropyridine Receptor2
HOKPP1 2     Dihydropyridine-Sensitive L-Type Calcium Channel Alpha-1 Subunit2
MHS51 2     hypoPP2
Voltage-Gated Calcium Channel Subunit Alpha Cav1.12 3     Voltage-Dependent L-Type Calcium Channel Subunit Alpha-1S2
CCHL1A32 5     CACH13
HOKPP12 5     CACN13
TTPP12 5     Calcium Channel, L Type, Alpha-1 Polypeptide, Isoform 3, Skeletal Muscle3
Cav1.12     

External Ids:    HGNC: 13971   Entrez Gene: 7792   Ensembl: ENSG000000812487   OMIM: 1142085   UniProtKB: Q136983   

Export aliases for CACNA1S gene to outside databases

Previous GC identifers: GC01M198738 GC01M196467 GC01M197475 GC01M198296 GC01M197740 GC01M199275 GC01M172185


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

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 paralysis, and hypokalemic periodic paralysis, and among its related super-pathways are Hypertrophic cardiomyopathy (HCM) and Parkinson's disease. 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 SCN5A.

UniProtKB/Swiss-Prot: CAC1S_HUMAN, Q13698
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

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 (Cav1.1) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000001.10  NT_004487.19  NC_018912.2  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the CACNA1S gene promoter:
         HOXA9   HOXA9B   GR   AML1a   C/EBPalpha   E47   Meis-1b   GR-alpha   Meis-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidCACNA1S promoter sequence
   Search SABiosciences Chromatin IP Primers for CACNA1S

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat CACNA1S


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1q32   Ensembl cytogenetic band:  1q32.1   HGNC cytogenetic band: 1q32

CACNA1S Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CACNA1S gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01M201008:  view genomic region     (about GC identifiers)

Start:
201,008,640 bp from pter      End:
201,081,694 bp from pter
Size:
73,055 bases      Orientation:
minus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: CAC1S_HUMAN, Q13698 (See protein sequence)
Recommended Name: Voltage-dependent L-type calcium channel subunit alpha-1S  
Size: 1873 amino acids; 212350 Da
Subunit: 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)
Subcellular location: Membrane; Multi-pass membrane protein
1 PDB 3D structure from and Proteopedia for CACNA1S:
2VAY (3D)    
Secondary accessions: A4IF51 B1ALM2 Q12896 Q13934

Explore the universe of human proteins at neXtProt for CACNA1S: NX_Q13698

Explore proteomics data for CACNA1S at MOPED 

Post-translational modifications:

  • UniProtKB: Phosphorylation by PKA activates the calcium channel (By similarity)
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q13698

  • CACNA1S Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    CACNA1S Protein Expression
    REFSEQ proteins: NP_000060.2  
    ENSEMBL proteins: 
     ENSP00000356307   ENSP00000355192  
    Reactome Protein details: Q13698
    Human Recombinant Protein Products for CACNA1S: 
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    Browse Sino Biological Cell Lysates 
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp. 

    Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm IDA11206130
    GO:0005886plasma membrane IDA11206130
    GO:0005891voltage-gated calcium channel complex IDA9852570
    GO:0016020membrane ----
    GO:0016529sarcoplasmic reticulum IEA--

    CACNA1S for ontologies           About GeneDecksing



    CACNA1S Antibody Products: 
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    Assay Products for CACNA1S: 
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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    HGNC Gene Families: 
    CACN: Calcium channel subunits
    CACN1: Voltage-gated ion channels / Calcium channels

    IUPHAR Guide to PHARMACOLOGY protein family classification: Cav1.1 
    Voltage-gated calcium channels

    5/6 InterPro protein domains (see all 6):
     IPR005446 VDCC_L_a1su
     IPR027359 K_channel_four-helix_dom
     IPR002077 VDCCAlpha1
     IPR005450 VDCC_L_a1ssu
     IPR014873 VDCC_a1su_IQ

    Graphical View of Domain Structure for InterPro Entry Q13698

    ProtoNet protein and cluster: Q13698

    3 Blocks protein domains:
    IPB002077 Calcium channel signature
    IPB005446 L-type voltage-dependent calcium channel alpha-1 subunit signature
    IPB005450 Voltage-dependent L-type calcium channel alpha-1S subunit signature


    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
    Domain: 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
    Similarity: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1S subfamily


    CACNA1S for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CAC1S_HUMAN, Q13698
    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

         Genatlas biochemistry entry for CACNA1S:
    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)

         Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005216ion channel activity ----
    GO:0005245voltage-gated calcium channel activity IDA9852570
    GO:0008331high voltage-gated calcium channel activity IDA9852570
    GO:0046872metal ion binding IEA--
         
    CACNA1S for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for CACNA1S:
     Synthetic lethal with c-Myc af 

         12 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Cacna1s):
     adipose tissue  behavior/neurological  craniofacial  digestive/alimentary  growth/size 
     homeostasis/metabolism  integument  limbs/digits/tail  mortality/aging  muscle 
     nervous system  skeleton 

    CACNA1S for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Cacna1stm1(KOMP)Vlcg for CACNA1S

       inGenious Targeting Laboratory - Custom generated mouse model solutions for CACNA1S 
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for CACNA1S 
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    miRNA
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    Inhib. RNA
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    Clone
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CACNA1S


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for CACNA1S About   (see all 36)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Hypertrophic cardiomyopathy (HCM)
    Hypertrophic cardiomyopathy (HCM)0.75
    Arrhythmogenic right ventricular cardiomyopathy (ARVC)0.54
    Dilated cardiomyopathy0.75
    Arrhythmogenic right ventricular cardiomyopathy0.53
    2Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.
    Alzheimer's disease0.46
    Alzheimers Disease0.44
    3PKC-Theta Pathway
    TCR Signaling0.68
    Fc-EpsilonRI Pathway0.49
    PKC-Theta Pathway0.68
    PDGF Pathway0.39
    ITK and TCR Signaling0.54
    4DREAM Repression and Dynorphin Expression
    DREAM Repression and Dynorphin Expression0.44
    Caspase Cascade0.36
    BMP Pathway0.44
    Calpain Protease Regulates Cellular Mechanics0.31
    nNOS Signaling in Skeletal Muscle0.37
    5Circadian entrainment
    GABAergic synapse0.53
    Cholinergic synapse0.37
    Retrograde endocannabinoid signaling0.51
    Serotonergic synapse0.33

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    3 EMD Millipore Pathways for CACNA1S
        Synaptic transmission- ion currents
    Transcription CREB pathway
    Calcium channels

    5/40 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for CACNA1S (see all 40)
        Caspase Cascade
    Fc-GammaR Pathway
    Intracellular Calcium Signaling
    PDGF Pathway
    BMP Pathway

    1 GeneGo (Thomson Reuters) Pathway for CACNA1S
        Transcription CREB pathway

    3 BioSystems Pathways for CACNA1S
        Calcium Regulation in the Cardiac Cell
    Alzheimers Disease
    Arrhythmogenic right ventricular cardiomyopathy

    4        Reactome Pathways for CACNA1S
        Developmental Biology
    NCAM1 interactions
    NCAM signaling for neurite out-growth
    Axon guidance

    2 PharmGKB Pathways for CACNA1S
        Beta-agonist/Beta-blocker Pathway, Pharmacodynamics
    Celecoxib Pathway, Pharmacodynamics

    5/14         Kegg Pathways  (Kegg details for CACNA1S) (see all 14):
        MAPK signaling pathway
    Calcium signaling pathway
    Cardiac muscle contraction
    Vascular smooth muscle contraction
    Retrograde endocannabinoid signaling


    CACNA1S for pathways           About GeneDecksing

    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for CACNA1S

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    5/124 Interacting proteins for CACNA1S (Q136982, 3 ENSP000003551924) via UniProtKB, MINT, STRING, and/or I2D (see all 124)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    YWHAQP273482, 3, ENSP000002380814MINT-7899812 I2D: score=1 STRING: ENSP00000238081
    RYR1P218173, ENSP000003526084I2D: score=1 STRING: ENSP00000352608
    RIMS2Q9UQ263, ENSP000003862284I2D: score=1 STRING: ENSP00000386228
    SRIP306263, ENSP000002657294I2D: score=2 STRING: ENSP00000265729
    YWHAZP631042, ENSP000003095034MINT-7899812 STRING: ENSP00000309503
    About this table

    Gene Ontology (GO): 5/15 biological process terms (GO ID links to tree view) (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001501skeletal system development IEA--
    GO:0002074extraocular skeletal muscle development IEA--
    GO:0006811ion transport ----
    GO:0006816calcium ion transport IDA9852570
    GO:0006936muscle contraction IMP17418573

    CACNA1S for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    CACNA1S for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Compounds for CACNA1S available from Tocris Bioscience    About this table
    CompoundAction CAS #
    omega-Conotoxin GVIACa2+ channel blocker (N-type)[106375-28-4]
    (+-)-Bay K 8644Ca2+-channel activator (L-type)[71145-03-4]
    NNC 55-0396 dihydrochlorideHighly selective Ca2+ channel blocker (T-type)[357400-13-6]
    PregabalinAnticonvulsant. Selectively binds the alpha2delta subunit of voltage-sensitive calcium channels[148553-50-8]
    Mibefradil dihydrochlorideCa2+ channel blocker (T-type)[116644-53-2]

    2 HMDB Compounds for CACNA1S    About this table
    CompoundSynonyms CAS #PubMed Ids
    CalciumCa (see all 2)7440-70-2--
    VerapamilAkilen (see all 107)52-53-9--

    10/14 DrugBank Compounds for CACNA1S (see all 14)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    NimodipineNimodipino [INN-Spanish] (see all 2)66085-59-4targetinhibitor20335610 17705883 20334460 19844625 16675661 20661350
    Mibefradil-- 116644-53-2targetinhibitor10372226 10665814 16899990
    Cinnarizine-- 298-57-7targetinhibitor3530295 1281221
    Magnesium SulfateBitter salt (see all 6)7487-88-9target--17139284 17016423
    AmlodipineAmlodipine Benzenesulfonate (see all 6)88150-42-9targetinhibitor16675661
    Clevidipine-- 166432-28-6target--15492770
    FelodipineDl-Felodipine (see all 4)72509-76-3targetinhibitor16675661
    Isradipine(+/-)-Isradipine (see all 5)75695-93-1targetinhibitor16675661
    Nifedipine-- 21829-25-4targetinhibitor16675661
    Nilvadipine-- 75530-68-6targetinhibitor16675661

    8 IUPHAR Ligands for CACNA1S (Cav1.1)    About this table 
    LigandTypeActionAffinityPubmed IDs
    [3H](+)-isradipine
    Gating inhibitorAntagonist9.72411596
    diltiazem
    Channel blockerNone9.7--
    SZ(+)-(S)-202-791
    ActivatorNone9.7--
    calciseptine
    Channel blockerNone9.7--
    FPL64176
    ActivatorNone9.7--
    (-)-(S)-BayK8644
    ActivatorNone9.7--
    nifedipine
    Channel blockerNone9.7--
    verapamil
    Channel blockerNone9.7--

    6 Novoseek inferred chemical compound relationships for CACNA1S gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    dihydropyridine 78.1 11 7847370 (2), 8118099 (1), 9132138 (1), 9436445 (1) (see all 9)
    ryanodine 63.4 1 19191329 (1)
    calcium 61.5 37 20431982 (3), 8188298 (2), 17223993 (2), 8838325 (2) (see all 31)
    sodium 40.4 3 10599760 (1), 19708131 (1), 17185904 (1)
    histidine 38.1 2 8845715 (1), 15185439 (1)
    arginine 25.6 2 10599760 (1), 15185439 (1)

    Search CenterWatch for drugs/clinical trials and news about CACNA1S / CAC1S

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
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    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for CACNA1S gene: 
    NM_000069.2  

    Unigene Cluster for CACNA1S:

    Calcium channel, voltage-dependent, L type, alpha 1S subunit
    Hs.1294  [show with all ESTs]
    Unigene Representative Sequence: NM_000069
    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000367338 ENST00000362061(uc001gvv.3)
    miRNA
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    Additional mRNA sequence: 

    BC133671.1 L33798.1 U09784.1 U14413.1 U18986.1 

    1 DOTS entry:

    DT.408105 

    24/28 AceView cDNA sequences (see all 28):

    U18986 BX104252 AW139004 U14413 AI740911 CF552495 AJ346015 F15900 
    U09784 NM_000069 L33798 F27669 BV168944 AJ572129 AI417964 BX500307 
    AI391509 F32453 AJ572253 BG986686 F20511 AA196212 AI073829 BQ359263 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    CACNA1S expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ATTGGATGGA
    CACNA1S Expression
    About this image


    See CACNA1S Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for CACNA1S

    SOURCE GeneReport for Unigene cluster: Hs.1294

    UniProtKB/Swiss-Prot: CAC1S_HUMAN, Q13698
    Tissue specificity: Skeletal muscle specific

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CACNA1S

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for CACNA1S gene from 7/13 species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Cacna1s1 , 5 calcium channel, voltage-dependent, L type, alpha 1S more1, 5 88.2(n)1
    92.45(a)1
      1 (59.55 cM)5
    122921  NM_001081023.11  NP_001074492.11 
     1360527505 
    chicken
    (Gallus gallus)
    Aves CACNA1S1 calcium channel, voltage-dependent, L type, alpha 1S more 78.08(n)
    81.27(a)
      395985  XM_419259.3  XP_419259.3 
    lizard
    (Anolis carolinensis)
    Reptilia CACNA1S6
    calcium channel, voltage-dependent, L type, alpha ...
    77(a)
    1 ↔ 1
    4(124468798-124552020)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.110942 Xenopus laevis skeletal muscle calcium channel alpha more 78.12(n)    AF421880.1 
    zebrafish
    (Danio rerio)
    Actinopterygii cacna1sa1 calcium channel, voltage-dependent, L type, alpha 1S more 72.02(n)
    74.76(a)
      570683  NM_001146150.1  NP_001139622.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Ca-alpha1D3 epithelial fluid transport
    voltage-gated calcium more
    58(a)     --
    worm
    (Caenorhabditis elegans)
    Secernentea egl-193 Expression: neurons, preanal ganglion,
    ring neurons, more
    61(a)
    (best of 2)
      IV(7405770-7418097)   --


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for CACNA1S gene
    SCN5A2  SCN9A2  CACNA1D2  SCN7A2  CACNA1I2  CACNA1F2  CACNA1G2  SCN8A2  
    SCN10A2  SCN3A2  SCN2A2  CACNA1H2  CACNA1C2  SCN11A2  SCN4A2  SCN1A2  
    10 SIMAP similar genes for CACNA1S using alignment to 2 protein entries:     CAC1S_HUMAN (see all proteins):
    CACNA1D    CACNA1C    CACNA1F    CACNA1H    SCN5A    SCN3A
    CACNA1B    SCN4A    CACNA1A    CACNA1E

    CACNA1S for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/2140 SNPs in CACNA1S are shown (see all 2140)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0014994
    Periodic paralysis hypokalemic 1 (HOKPP1)4--see VAR_0014992 R H mis40--------
    VAR_0549544
    Periodic paralysis hypokalemic 1 (HOKPP1)4--see VAR_0549542 R S mis40--------
    VAR_0549534
    Periodic paralysis hypokalemic 1 (HOKPP1)4--see VAR_0549532 R G mis40--------
    rs289300681,2,4
    CPeriodic paralysis hypokalemic 1 (HOKPP1)4 pathogenic1207560056(-) GTTCCA/GTGTCA 2 H R mis1 ese30--------
    rs289300691,2,4
    CPeriodic paralysis hypokalemic 1 (HOKPP1)4 pathogenic1207560057(-) TGTTCC/GGTGTC 2 R G mis1 ese30--------
    rs18005591,2,4
    CMalignant hyperthermia 5 (MHS5)4 pathogenic1207567334(-) ACAGCA/GCCAAT 2 H R mis10--------
    rs803387821,2
    Cpathogenic1207567335(-) CACAGA/C/TGCCAA 3 S R C mis10--------
    rs803387791,2
    Cpathogenic1207572803(-) CTGAGG/TGTGCT 2 R S mis10--------
    rs803387771,2
    Cpathogenic1207584435(-) GCTCCA/GCTGCA 2 H R mis10--------
    rs803387781,2
    Cpathogenic1207584436(-) TGCTCC/G/TGCTGC 2 R G mis10--------

    HapMap Linkage Disequilibrium report for CACNA1S (201008640 - 201081694 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for CACNA1S:    About this table     
    Variant IDTypeSubtypePubMed ID
    esv1000350CNV Deletion20482838
    nsv4054CNV Insertion18451855
    nsv515571CNV Loss19592680
    nsv428301CNV Gain18775914


    Human Gene Mutation Database (HGMD): CACNA1S

    Locus Specific Mutation Databases (LSDB): CACNA1S
    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 114208   
    OMIM disorders: 170400  601887  188580  
    UniProtKB/Swiss-Prot: CAC1S_HUMAN, Q13698
  • 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. 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.
    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.
    Note=Disease susceptibility is associated with variations affecting the gene represented in this entry

  • 20/28 diseases for CACNA1S (see all 28):    About MalaCards
    paralysis    hypokalemic periodic paralysis    thyrotoxic periodic paralysis    hypokalemic periodic paralysis type 1
    cacna1s-related malignant hyperthermia susceptibility    malignant hyperthermia susceptibility type 5    thyrotoxic periodic paralysis 1    malignant hyperthermia
    malignant hyperthermia susceptibility    thomsen disease    central core myopathy    periodic paralyses
    hyperkalemic periodic paralysis    hypokalemia    hyperuricemia    myasthenia gravis
    maturity-onset diabetes of the young    graves' disease    myotonic dystrophy    myopathy

    3 diseases from the University of Copenhagen DISEASES database for CACNA1S:
    Malignant hyperthermia     Myopathy     Hypokalemia

    CACNA1S for disorders           About GeneDecksing

    5 Novoseek inferred disease relationships for CACNA1S gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    hypokalemic periodic paralysis 97.5 21 19822448 (2), 9436445 (2), 19118277 (2), 10599760 (2) (see all 16)
    periodic paralysis 92.1 6 17223993 (2), 16767662 (2), 15185439 (1), 18835861 (1)
    central core disease 79 1 11216663 (1)
    hypokalemia 56.2 1 15185439 (1)
    paralysis 52.4 2 20080402 (1)

    GeneTests: CACNA1S
    GeneReviews: CACNA1S
    Genetic Association Database (GAD): CACNA1S
    Human Genome Epidemiology (HuGE) Navigator: CACNA1S (6 documents)

    Export disorders for CACNA1S gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for CACNA1S gene, integrated from 9 sources (see all 110):
    (articles sorted by number of sources associating them with CACNA1S)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Assignment of the human gene for the alpha-1 subunit of the skeletal muscle DHP-sensitive calcium channel (CACNL1A3) to chromosome 1q31- q32. (PubMed id 7916735)1, 2, 3, 9 Gregg R.G.... Powers P.A. (1993)
    2. The role of CACNA1S in predisposition to malignant hy perthermia. (PubMed id 19825159)1, 4, 9 Carpenter D....Shaw M.A. (2009)
    3. Skeletal muscle dihydropyridine-sensitive calcium channel (CACNA1S) gene mutations in chinese patients with hypokalemic periodic paralysis. (PubMed id 15711422)1, 4, 9 Lin S.H....Kao M.C. (2005)
    4. The structure of the gene encoding the human skeletal muscle alpha 1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3). (PubMed id 8838325)1, 2, 9 Hogan K.... Powers P.A. (1996)
    5. Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. (PubMed id 19118277)1, 2, 9 Matthews E....Hanna M.G. (2009)
    6. Increasing the number of diagnostic mutations in malignant hyperthermia. (PubMed id 19191329)1, 4, 9 Levano S....Girard T. (2009)
    7. Cloning of the human skeletal muscle alpha 1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3). (PubMed id 7713519)1, 2, 9 Hogan K.... Gregg R.G. (1994)
    8. 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. (PubMed id 9199552)1, 2, 9 Monnier N.... Lunardi J. (1997)
    9. Genome-wide association study identifies four loci ass ociated with eruption of permanent teeth. (PubMed id 21931568)1, 4 Geller F....Melbye M. (2011)
    10. L-type voltage-dependent calcium channel alpha subuni t 1C is a novel candidate gene associated with secondary hyperparathyroidism: a n application of haplotype-based analysis for multiple linked single nucleotide polymorphisms. (PubMed id 20424473)1, 4 Yokoyama K....Hosoya T. (2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 779 HGNC: 1397 AceView: CACNA1S Ensembl:ENSG00000081248 euGenes: HUgn779
    ECgene: CACNA1S Kegg: 779 H-InvDB: CACNA1S

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for CACNA1S Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CACNA1S

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for CACNA1S gene:
    Search GeneIP for patents involving CACNA1S

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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    About This Section

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