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    CACNA1S calcium channel, voltage-dependent, L type, alpha 1S subunit [ Homo sapiens ]

    Gene ID: 779, updated on 19-May-2012
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    Summary

    Official Symbol
    CACNA1Sprovided by HGNC
    Official Full Name
    calcium channel, voltage-dependent, L type, alpha 1S subunitprovided by HGNC
    Primary source
    HGNC:1397
    See related
    Ensembl:ENSG00000081248; HPRD:00248; MIM:114208; Vega:OTTHUMG00000035784
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MHS5; HOKPP; TTPP1; Cav1.1; HOKPP1; hypoPP; CCHL1A3; CACNL1A3
    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 malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    1q32
    Sequence :
    Chromosome: 1; NC_000001.10 (201008640..201081694, complement)
    See CACNA1S in Epigenomics, MapViewer

    Chromosome 1 - NC_000001.10Genomic Context describing neighboring genes Neighboring gene kinesin family member 21B Neighboring gene uncharacterized LOC100506546 Neighboring gene transmembrane protein 9 Neighboring gene immunoglobulin-like and fibronectin type III domain containing 1

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Genotype and phenotype analysis of patients with sporadic periodic paralysis. Sung CC, et al. Am J Med Sci, 2012 Apr. PMID 21841462.
    2. [The relationships between the single nueleotide polymorphisms of CACNA1S gene 11 exon and thyrotoxic hypokalemic periodic paralysis in the people of Han Nationality in Sichuan Province, China]. Xiao Z, et al. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2011 Jun. PMID 21774221.
    3. Functional expression of transgenic 1sDHPR channels in adult mammalian skeletal muscle fibres. DiFranco M, et al. J Physiol, 2011 Mar 15. PMID 21262876.
    4. Clinical utility gene card for: malignant hyperthermia. Rosenberg H, et al. Eur J Hum Genet, 2011 Jun. PMID 21248738.
    5. Identification and functional characterization of malignant hyperthermia mutation T1354S in the outer pore of the Cavalpha1S-subunit. Pirone A, et al. Am J Physiol Cell Physiol, 2010 Dec. PMID 20861472.

    See all (46) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. All familial periodic paralysis patients studied have mutations in either CACNA1S or SCN4A, but only 4 sporadic periodic paralysis patients have de novo mutations in CACNA1S (R1239H) and SCN4A (R669x2, R1135H).
      Title: Genotype and phenotype analysis of patients with sporadic periodic paralysis.
    2. Three SNPs of CACNA1S gene exon 11 were found but could not be associated with thyrotoxic hypokalemic periodic paralysis in people of Han Nationality in Sichuan.
      Title: [The relationships between the single nueleotide polymorphisms of CACNA1S gene 11 exon and thyrotoxic hypokalemic periodic paralysis in the people of Han Nationality in Sichuan Province, China].
    3. Expression of transgenic variants of dihydropyridine receptor (alpha1DHPR) subunit leads to replacement of native channels interacting with ryanodine receptor 1 (RyR1), demonstrating molecular remodelling in adult skeletal muscle fibers.
      Title: Functional expression of transgenic 1sDHPR channels in adult mammalian skeletal muscle fibres.
    4. Mutations in the affected genes cause Malignant Hyperthermia.
      Title: Clinical utility gene card for: malignant hyperthermia.
    5. All individuals in the Italian family with malignant hyperthermia showed cosegregation of informative markers close to the voltage-dependent Ca2+ channel alpha-1S-subunit gene. Sequence analysis showed a c.4060A>T transversion.
      Title: Identification and functional characterization of malignant hyperthermia mutation T1354S in the outer pore of the Cavalpha1S-subunit.
    6. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    7. Results identify a new mutation in CACNA1S and expand the spectrum of CACNA1S mutations associated with HypoPP.
      Title: Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a South American family.
    8. Ca(V)1.1 Delta 29 splice variant revealed the structural bases underlying the specific gating properties of skeletal muscle Ca(2+) channels, and suggests the existence of a distinct mode of excitation-contraction coupling in developing muscle
      Title: A CaV1.1 Ca2+ channel splice variant with high conductance and voltage-sensitivity alters EC coupling in developing skeletal muscle.
    9. The study identified a single potentially pathogenic change in CACNA1S (p.Arg174Trp), and highlights that the haplotype structure across CACNA1S is diverse, with a high degree of variability
      Title: The role of CACNA1S in predisposition to malignant hyperthermia.
    10. All mutations affected CACNA1S arginine residues, consistent with the gating pore cation leak hypothesis of hypokalemic periodic paralysis. Arginine mutations in S4 segments underlie 90% of hypokalemic periodic paralysis cases.
      Title: Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis.
    Submit: New GeneRIF Correction See all (17)
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    Phenotypes

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Hypokalemic periodic paralysis, type 1

    Summary from GeneReviews: Go to GeneReviews

    Disease Characteristics
    Hypokalemic periodic paralysis (HOKPP) is characterized by a paralytic form and a myopathic form. The paralytic form is characterized by attacks of reversible flaccid paralysis with concomitant hypokalemia, usually leading to paraparesis or tetraparesis but sparing the respiratory muscles and heart. Acute paralytic crises usually last at least several hours and sometimes days. Some individuals have only one episode in a lifetime; more commonly, crises occur repeatedly: daily, weekly, monthly, or less often. The major triggering factors are carbohydrate-rich meals and rest after exercise; rarely, cold-induced hypokalemic paralysis has been reported. The interval between crises may vary and may be prolonged by preventive treatment with potassium salts or acetazolamide. The age of onset of the first attack ranges from one to 20 years; the frequency of attacks is highest between ages 15 and 35 and then decreases with age. The myopathic form develops in approximately 25% of affected individuals and results in a progressive fixed muscle weakness that begins at variable ages as exercise intolerance predominantly in the lower limbs. It occurs independent of paralytic symptoms and may be the sole manifestation of HOKPP. Individuals with HOKPP are at increased risk for pre- or post-anesthetic weakness and have a risk for malignant hyperthermia that is increased but not as high as that for individuals with true autosomal dominant malignant hyperthermia susceptibility (MHS).
    Diagnosis Testing
    The diagnosis of HOKPP is based on a history of episodes of flaccid paralysis; low serum concentration of potassium (<0.9 to 3.0 mmol/L) during attacks, but not between attacks; the absence of myotonia clinically and on electromyography (EMG) (with the exception of one family with heat-induced myotonia and cold-induced HOKPP); the absence of hyperthyroidism; the absence of dysmorphic traits and cardiac arrhythmias; and a family history consistent with autosomal dominant inheritance. Of all individuals meeting diagnostic criteria for HOKPP, approximately 55%-70% have mutations in CACNA1S and approximately 8%-10% in SCN4A. Molecular genetic testing is clinically available.
    Genetic Counseling
    HOKPP is inherited in an autosomal dominant manner. Most individuals diagnosed with HOKPP have an affected parent. The proportion of cases caused by a de novo gene mutation is unknown. Offspring of a proband have a 50% risk of inheriting the mutation. Penetrance is about 90% in males and may be as low as 50% in females depending on the causative mutation. Prenatal testing is possible if the disease-causing mutation has been identified in the family; however, requests for prenatal testing for conditions such as HOKPP that do not affect intellect and have some treatment available are not common.
    References

    Malignant hyperthermia susceptibility 5

    Thyrotoxic periodic paralysis, susceptibility to, 1

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Q13698 Q9UQ26 RIMS2    HPRD  PubMed  
    Q13698 P21817 RYR1    HPRD  PubMed  
    Q13698 P30626 SRI    HPRD  PubMed  
    BioGRID:107233 BioGRID:112595 SRI    BioGRID  PubMed Reconstituted Complex 
    BioGRID:107233 BioGRID:116168 YWHAQ    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Alzheimer's disease, organism-specific biosystem (from KEGG)
      Alzheimer's disease, organism-specific biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
    • Alzheimer's disease, conserved biosystem (from KEGG)
      Alzheimer's disease, conserved biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
    • Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystem (from KEGG)
      Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
    • Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystem (from KEGG)
      Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
    • Axon guidance, organism-specific biosystem (from REACTOME)
      Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
    • Calcium Regulation in the Cardiac Cell, organism-specific biosystem (from WikiPathways)
      Calcium Regulation in the Cardiac Cell, organism-specific biosystemCalcium is a common signaling mechanism, as once it enters the cytoplasm it exerts allosteric regulatory affects on many enzymes and proteins. Calcium can act in signal transduction after influx resu...
    • Calcium signaling pathway, organism-specific biosystem (from KEGG)
      Calcium signaling pathway, organism-specific biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
    • Calcium signaling pathway, conserved biosystem (from KEGG)
      Calcium signaling pathway, conserved biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
    • Cardiac muscle contraction, organism-specific biosystem (from KEGG)
      Cardiac muscle contraction, organism-specific biosystemContraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation...
    • Cardiac muscle contraction, conserved biosystem (from KEGG)
      Cardiac muscle contraction, conserved biosystemContraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation...
    • Cholinergic synapse, organism-specific biosystem (from KEGG)
      Cholinergic synapse, organism-specific biosystemAcetylcholine (ACh) is a neurotransmitter widely distributed in the central (and also peripheral, autonomic and enteric) nervous system (CNS). In the CNS, ACh facilitates many functions, such as lear...
    • Developmental Biology, organism-specific biosystem (from REACTOME)
      Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
    • Dilated cardiomyopathy, organism-specific biosystem (from KEGG)
      Dilated cardiomyopathy, organism-specific biosystemDilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac d...
    • Dilated cardiomyopathy, conserved biosystem (from KEGG)
      Dilated cardiomyopathy, conserved biosystemDilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac d...
    • GABAergic synapse, organism-specific biosystem (from KEGG)
      GABAergic synapse, organism-specific biosystemGamma aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the mammalian central nervous system (CNS). When released in the synaptic cleft, GABA binds to three major classes o...
    • GABAergic synapse, conserved biosystem (from KEGG)
      GABAergic synapse, conserved biosystemGamma aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the mammalian central nervous system (CNS). When released in the synaptic cleft, GABA binds to three major classes o...
    • GnRH signaling pathway, organism-specific biosystem (from KEGG)
      GnRH signaling pathway, organism-specific biosystemGonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnR...
    • GnRH signaling pathway, conserved biosystem (from KEGG)
      GnRH signaling pathway, conserved biosystemGonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnR...
    • Hypertrophic cardiomyopathy (HCM), organism-specific biosystem (from KEGG)
      Hypertrophic cardiomyopathy (HCM), organism-specific biosystemHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological feat...
    • Hypertrophic cardiomyopathy (HCM), conserved biosystem (from KEGG)
      Hypertrophic cardiomyopathy (HCM), conserved biosystemHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological feat...
    • MAPK signaling pathway, organism-specific biosystem (from KEGG)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MAPK signaling pathway, conserved biosystem (from KEGG)
      MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • NCAM signaling for neurite out-growth, organism-specific biosystem (from REACTOME)
      NCAM signaling for neurite out-growth, organism-specific biosystemThe neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the n...
    • NCAM1 interactions, organism-specific biosystem (from REACTOME)
      NCAM1 interactions, organism-specific biosystemThe neural cell adhesion molecule, NCAM1 is generally considered as a cell adhesion mediator, but it is also considered to be a signal transducing receptor molecule. NCAM1 is involved in multiple cis...
    • Retrograde endocannabinoid signaling, organism-specific biosystem (from KEGG)
      Retrograde endocannabinoid signaling, organism-specific biosystemEndogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. The family of endocannabinoids includes at least five derivatives of arachidonic...
    • Retrograde endocannabinoid signaling, conserved biosystem (from KEGG)
      Retrograde endocannabinoid signaling, conserved biosystemEndogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. The family of endocannabinoids includes at least five derivatives of arachidonic...
    • Serotonergic synapse, organism-specific biosystem (from KEGG)
      Serotonergic synapse, organism-specific biosystemSerotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter that plays important roles in physiological functions such as learning and memory, emotion, sleep, pain, motor function and endoc...
    • Vascular smooth muscle contraction, organism-specific biosystem (from KEGG)
      Vascular smooth muscle contraction, organism-specific biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...
    • Vascular smooth muscle contraction, conserved biosystem (from KEGG)
      Vascular smooth muscle contraction, conserved biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    high voltage-gated calcium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    voltage-gated calcium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    voltage-gated ion channel activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    axon guidance TAS
    Traceable Author Statement
    more info
    		  
    calcium ion transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    endoplasmic reticulum organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    extraocular skeletal muscle development IEA
    Inferred from Electronic Annotation
    more info
    		  
    ion transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    muscle cell development IEA
    Inferred from Electronic Annotation
    more info
    		  
    muscle contraction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    myoblast fusion IEA
    Inferred from Electronic Annotation
    more info
    		  
    neuromuscular junction development IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of calcium ion transport via voltage-gated calcium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    skeletal muscle adaptation IEA
    Inferred from Electronic Annotation
    more info
    		  
    skeletal system development IEA
    Inferred from Electronic Annotation
    more info
    		  
    striated muscle contraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    I band IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    T-tubule IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    integral to membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    sarcoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    voltage-gated calcium channel complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    voltage-dependent L-type calcium channel subunit alpha-1S
    Names
    voltage-dependent L-type calcium channel subunit alpha-1S
    dihydropyridine receptor
    voltage-gated calcium channel subunit alpha Cav1.1
    dihydropyridine-sensitive L-type calcium channel alpha-1 subunit
    calcium channel, L type, alpha 1 polypeptide, isoform 3 (skeletal muscle, hypokalemic periodic paralysis)
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_009816.1 RefSeqGene

      Range
      5001..78055
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000069.2 → NP_000060.2  voltage-dependent L-type calcium channel subunit alpha-1S

      Status: REVIEWED

      Source sequence(s)
      AL139159, AL358473
      Consensus CDS
      CCDS1407.1
      UniProtKB/Swiss-Prot
      Q13698
      Related
      ENSP00000355192, OTTHUMP00000033931, ENST00000362061, OTTHUMT00000087049
      Conserved Domains (3) summary
      cl07394
      Location:1516 – 1542
      Blast Score: 149
      Ca_chan_IQ; Voltage gated calcium channel IQ domain
      pfam00520
      Location:1152 – 1380
      Blast Score: 444
      Ion_trans; Ion transport protein
      pfam08016
      Location:1152 – 1385
      Blast Score: 161
      PKD_channel; Polycystin cation channel

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000001.10 Reference GRCh37.p5 Primary Assembly

      Range
      201008640..201081694, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000133.1 Alternate HuRef

      Range
      172175337..172248318, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL139159.10 CAI23206.1
      CAI23207.1
    genomic AL358473.10 CAI12386.1
      CAI12387.1
    genomic CH471067.1 EAW91333.1
      EAW91334.1
      EAW91335.1
    genomic U30707.1 AAB37235.1
    mRNA BC133671.1 AAI33672.1
    mRNA L33798.1 AAA51902.1
    mRNA U09784.1 AAA20531.1
    mRNA U14413.1 AAC50397.1
    mRNA U18986.1 AAC50398.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q12966 GenPept UniProtKB/TrEMBL:Q12966
    Q13062 GenPept UniProtKB/TrEMBL:Q13062
    Q13698.4 GenPept UniProtKB/Swiss-Prot:Q13698
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
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