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Genetics Home Reference: your guide to understanding genetic conditions
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CACNA1S

Reviewed October 2007

What is the official name of the CACNA1S gene?

The official name of this gene is “calcium channel, voltage-dependent, L type, alpha 1S subunit.”

CACNA1S is the gene's official symbol. The CACNA1S gene is also known by other names, listed below.

What is the normal function of the CACNA1S gene?

The CACNA1S gene belongs to a family of genes that provide instructions for making calcium channels. These channels, which transport positively charged calcium atoms (ions) into cells, play a key role in a cell's ability to generate and transmit electrical signals.

The CACNA1S gene provides instructions for making calcium channels that are abundant in muscles used for movement (skeletal muscles). For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain ions into muscle cells. Channels made with the CACNA1S protein control the transport of calcium ions into muscle cells and are part of the cellular machinery that initiates muscle contractions.

Channels made with the CACNA1S protein also activate a protein called ryanodine receptor 1 (produced by the RYR1 gene). Ryanodine receptor 1 forms a channel that releases stored calcium ions within muscle cells in response to certain signals. The resulting increase in calcium ion concentration stimulates muscle fibers to contract, allowing the body to move.

Does the CACNA1S gene share characteristics with other genes?

The CACNA1S gene belongs to a family of genes called CACN (calcium channels).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the CACNA1S gene related to health conditions?

hypokalemic periodic paralysis - caused by mutations in the CACNA1S gene

At least four mutations in the CACNA1S gene have been identified in people with hypokalemic periodic paralysis. These mutations cause up to 70 percent of all cases of this disorder.

Mutations in the CACNA1S gene change single protein building blocks (amino acids) used to make the CACNA1S protein, which alters the structure and function of calcium channels in skeletal muscle cells. The altered channels open more slowly than usual, reducing the flow of calcium ions into these cells. This disruption in calcium ion transport prevents muscles from contracting normally. It is unclear precisely how these changes lead to episodes of muscle weakness in people with hypokalemic periodic paralysis.

malignant hyperthermia - increased risk from variations of the CACNA1S gene

CACNA1S mutations account for a very small percentage of all cases of malignant hyperthermia. Researchers have identified two mutations in the CACNA1S gene that are associated with an increased risk of this condition. One of these mutations replaces the amino acid arginine with the amino acid cysteine at protein position 1086 (written as Arg1086Cys); the other mutation replaces the amino acid arginine with the amino acid histidine at the same protein position (Arg1086His).

Genetic mutations likely cause channels made with the CACNA1S protein to activate the RYR1 channel improperly in response to certain drugs (particularly some anesthetics and a type of muscle relaxant used during surgery). As a result, large amounts of calcium ions are released from storage within muscle cells. An overabundance of available calcium ions causes skeletal muscles to contract abnormally, which leads to muscle rigidity in people with malignant hyperthermia. An increase in calcium ion concentration also activates processes that generate heat (leading to increased body temperature) and produce excess acid (leading to acidosis).

Where is the CACNA1S gene located?

Cytogenetic Location: 1q32

Molecular Location on chromosome 1: base pairs 201,039,506 to 201,112,565

The CACNA1S gene is located on the long (q) arm of chromosome 1 at position 32.

The CACNA1S gene is located on the long (q) arm of chromosome 1 at position 32.

More precisely, the CACNA1S gene is located from base pair 201,039,506 to base pair 201,112,565 on chromosome 1.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about CACNA1S?

You and your healthcare professional may find the following resources about CACNA1S helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the CACNA1S gene or gene products?

  • CAC1S_HUMAN
  • CACH1
  • CACN1
  • CACNL1A3
  • Cav1.1
  • CCHL1A3
  • DHPR
  • dihydropyridine receptor
  • dihydropyridine-sensitive L-type calcium channel alpha-1 subunit
  • HOKPP
  • HypoKPP
  • hypoPP
  • MHS5
  • Voltage-dependent L-type calcium channel subunit alpha-1S
  • voltage-gated calcium channel subunit alpha Cav1.1

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding CACNA1S?

acidosis ; acids ; amino acid ; anesthetics ; arginine ; calcium ; cell ; channel ; contraction ; cysteine ; gene ; histidine ; hyperthermia ; increased body temperature ; ions ; ion transport ; muscle cells ; muscle relaxant ; mutation ; protein ; receptor ; skeletal muscle ; subunit ; surgery ; voltage

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Fouad G, Dalakas M, Servidei S, Mendell JR, Van den Bergh P, Angelini C, Alderson K, Griggs RC, Tawil R, Gregg R, Hogan K, Powers PA, Weinberg N, Malonee W, Ptácek LJ. Genotype-phenotype correlations of DHP receptor alpha 1-subunit gene mutations causing hypokalemic periodic paralysis. Neuromuscul Disord. 1997 Jan;7(1):33-8. (http://www.ncbi.nlm.nih.gov/pubmed/9132138?dopt=Abstract)
  • Gene Review: Hypokalemic Periodic Paralysis (http://www.ncbi.nlm.nih.gov/books/NBK1338)
  • Gene Review: Malignant Hyperthermia Susceptibility (http://www.ncbi.nlm.nih.gov/books/NBK1146)
  • Lehmann-Horn F, Jurkat-Rott K, Rüdel R. Periodic paralysis: understanding channelopathies. Curr Neurol Neurosci Rep. 2002 Jan;2(1):61-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11898585?dopt=Abstract)
  • Miller TM, Dias da Silva MR, Miller HA, Kwiecinski H, Mendell JR, Tawil R, McManis P, Griggs RC, Angelini C, Servidei S, Petajan J, Dalakas MC, Ranum LP, Fu YH, Ptácek LJ. Correlating phenotype and genotype in the periodic paralyses. Neurology. 2004 Nov 9;63(9):1647-55. (http://www.ncbi.nlm.nih.gov/pubmed/15534250?dopt=Abstract)
  • Monnier N, Procaccio V, Stieglitz P, Lunardi J. 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. Am J Hum Genet. 1997 Jun;60(6):1316-25. (http://www.ncbi.nlm.nih.gov/pubmed/9199552?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/779)
  • Stewart SL, Hogan K, Rosenberg H, Fletcher JE. Identification of the Arg1086His mutation in the alpha subunit of the voltage-dependent calcium channel (CACNA1S) in a North American family with malignant hyperthermia. Clin Genet. 2001 Mar;59(3):178-84. (http://www.ncbi.nlm.nih.gov/pubmed/11260227?dopt=Abstract)
  • Venance SL, Cannon SC, Fialho D, Fontaine B, Hanna MG, Ptacek LJ, Tristani-Firouzi M, Tawil R, Griggs RC; CINCH investigators. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain. 2006 Jan;129(Pt 1):8-17. Epub 2005 Sep 29. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16195244?dopt=Abstract)
  • Wang Q, Liu M, Xu C, Tang Z, Liao Y, Du R, Li W, Wu X, Wang X, Liu P, Zhang X, Zhu J, Ren X, Ke T, Wang Q, Yang J. Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family. J Mol Med (Berl). 2005 Mar;83(3):203-8. Epub 2005 Feb 22. (http://www.ncbi.nlm.nih.gov/pubmed/15726306?dopt=Abstract)
  • Yamakage M, Namiki A. Calcium channels--basic aspects of their structure, function and gene encoding; anesthetic action on the channels--a review. Can J Anaesth. 2002 Feb;49(2):151-64. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11823393?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2007
Published: December 16, 2014