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Genetics Home Reference: your guide to understanding genetic conditions
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SCN1A

Reviewed January 2014

What is the official name of the SCN1A gene?

The official name of this gene is “sodium channel, voltage-gated, type I, alpha subunit.”

SCN1A is the gene's official symbol. The SCN1A gene is also known by other names, listed below.

What is the normal function of the SCN1A gene?

The SCN1A gene belongs to a family of genes that provide instructions for making sodium channels. These channels, which transport positively charged sodium atoms (sodium ions) into cells, play a key role in a cell's ability to generate and transmit electrical signals.

The SCN1A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.1. These channels are found in the brain and muscles, where they control the flow of sodium ions into cells. In the brain, NaV1.1 channels are involved in transmitting signals from one nerve cell (neuron) to another. Communication between neurons depends on chemicals called neurotransmitters, which are released from one neuron and taken up by neighboring neurons. The flow of sodium ions through NaV1.1 channels helps determine when neurotransmitters will be released.

Does the SCN1A gene share characteristics with other genes?

The SCN1A gene belongs to a family of genes called SC (sodium 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 SCN1A gene related to health conditions?

familial hemiplegic migraine - caused by mutations in the SCN1A gene

At least five mutations in the SCN1A gene have been identified in people with familial hemiplegic migraine type 3 (FHM3). Each of these mutations changes a single protein building block (amino acid) in the NaV1.1 channel, which alters the channel's structure. The abnormal channels stay open longer than usual, which increases the flow of sodium ions into neurons. This increase triggers the cell to release more neurotransmitters. The resulting changes in signaling between neurons make people with FHM3 more susceptible to developing these severe headaches.

other disorders - caused by mutations in the SCN1A gene

More than 150 mutations in the SCN1A gene have been associated with various seizure disorders that begin in infancy or childhood. Several of these conditions are relatively mild. These conditions include simple febrile (fever-associated) seizures, which start in infancy and usually stop by age 5, and generalized epilepsy with febrile seizures plus (GEFS+). GEFS+ involves febrile and other types of seizures that can persist beyond childhood. Other conditions cause more serious seizures that last longer and may be difficult to control. These recurrent seizures can worsen over time and lead to a decline in brain function. Severe seizure disorders caused by SCN1A mutations include severe myoclonic epilepsy of infancy (SMEI) and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC).

The SCN1A mutations that underlie seizure disorders have a variety of effects on the function of the NaV1.1 channel. The milder disorders are caused by mutations that change single amino acids in the channel, which alter the channel's structure. More severe seizure disorders can result from several different changes in the SCN1A gene. Some mutations lead to the production of a nonfunctional version of the NaV1.1 channel or reduce the number of these channels produced in each cell. Other mutations change single amino acids in critical regions of the channel. All of these genetic changes affect the ability of NaV1.1 channels to transport sodium ions into neurons. It is unclear, however, why these genetic changes lead to such a large range of seizure disorders.

A common change (polymorphism) in the SCN1A gene has been associated with the effectiveness of certain anti-seizure medications. This polymorphism, which is written as ICS5N+5G>A, alters a single DNA building block (nucleotide) in the SCN1A gene. Studies suggest that this polymorphism is associated with the maximum safe amount (dose) of the anti-seizure drugs phenytoin and carbamazepine. These drugs treat epilepsy by blocking sodium channels (such as NaV1.1) in neurons. A dose that is too small may not control seizures effectively, while a dose that is too large may cause unwanted side effects. Right now, doctors must use a trial-and-error approach to determine the correct dose for each person. Researchers are hopeful that doctors will one day be able to use the ICS5N+5G>A polymorphism to determine the safest and most effective dose of anti-seizure medications for each individual.

Where is the SCN1A gene located?

Cytogenetic Location: 2q24.3

Molecular Location on chromosome 2: base pairs 165,989,159 to 166,149,131

The SCN1A gene is located on the long (q) arm of chromosome 2 at position 24.3.

The SCN1A gene is located on the long (q) arm of chromosome 2 at position 24.3.

More precisely, the SCN1A gene is located from base pair 165,989,159 to base pair 166,149,131 on chromosome 2.

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 SCN1A?

You and your healthcare professional may find the following resources about SCN1A 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 SCN1A gene or gene products?

  • GEFSP2
  • HBSCI
  • NAC1
  • Nav1.1
  • SCN1
  • SCN1A_HUMAN
  • sodium channel protein, brain I alpha subunit
  • sodium channel, voltage-gated, type I, alpha
  • sodium channel, voltage-gated, type I, alpha polypeptide

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 SCN1A?

acids ; action potential ; amino acid ; carbamazepine ; cell ; channel ; DNA ; epilepsy ; familial ; fever ; gene ; hemiplegic ; ions ; migraine ; nerve cell ; neuron ; neurotransmitters ; nucleotide ; polymorphism ; protein ; seizure ; side effects ; sodium ; sodium channel ; subunit ; syndrome ; 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

  • Dichgans M, Freilinger T, Eckstein G, Babini E, Lorenz-Depiereux B, Biskup S, Ferrari MD, Herzog J, van den Maagdenberg AM, Pusch M, Strom TM. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet. 2005 Jul 30-Aug 5;366(9483):371-7. (http://www.ncbi.nlm.nih.gov/pubmed/16054936?dopt=Abstract)
  • Fujiwara T. Clinical spectrum of mutations in SCN1A gene: severe myoclonic epilepsy in infancy and related epilepsies. Epilepsy Res. 2006 Aug;70 Suppl 1:S223-30. Epub 2006 Jun 27. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16806826?dopt=Abstract)
  • Gargus JJ, Tournay A. Novel mutation confirms seizure locus SCN1A is also familial hemiplegic migraine locus FHM3. Pediatr Neurol. 2007 Dec;37(6):407-10. (http://www.ncbi.nlm.nih.gov/pubmed/18021921?dopt=Abstract)
  • Meisler MH, Kearney JA. Sodium channel mutations in epilepsy and other neurological disorders. J Clin Invest. 2005 Aug;115(8):2010-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16075041?dopt=Abstract)
  • Mulley JC, Scheffer IE, Petrou S, Dibbens LM, Berkovic SF, Harkin LA. SCN1A mutations and epilepsy. Hum Mutat. 2005 Jun;25(6):535-42. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15880351?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6323)
  • Pietrobon D. Familial hemiplegic migraine. Neurotherapeutics. 2007 Apr;4(2):274-84. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17395138?dopt=Abstract)
  • Tate SK, Depondt C, Sisodiya SM, Cavalleri GL, Schorge S, Soranzo N, Thom M, Sen A, Shorvon SD, Sander JW, Wood NW, Goldstein DB. Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5507-12. Epub 2005 Apr 1. (http://www.ncbi.nlm.nih.gov/pubmed/15805193?dopt=Abstract)
  • Tate SK, Singh R, Hung CC, Tai JJ, Depondt C, Cavalleri GL, Sisodiya SM, Goldstein DB, Liou HH. A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose. Pharmacogenet Genomics. 2006 Oct;16(10):721-6. (http://www.ncbi.nlm.nih.gov/pubmed/17001291?dopt=Abstract)
  • Vanmolkot KR, Babini E, de Vries B, Stam AH, Freilinger T, Terwindt GM, Norris L, Haan J, Frants RR, Ramadan NM, Ferrari MD, Pusch M, van den Maagdenberg AM, Dichgans M. The novel p.L1649Q mutation in the SCN1A epilepsy gene is associated with familial hemiplegic migraine: genetic and functional studies. Mutation in brief #957. Online. Hum Mutat. 2007 May;28(5):522. (http://www.ncbi.nlm.nih.gov/pubmed/17397047?dopt=Abstract)
  • Yamakawa K. Na channel gene mutations in epilepsy--the functional consequences. Epilepsy Res. 2006 Aug;70 Suppl 1:S218-22. Epub 2006 Jun 27. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16806834?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: January 2014
Published: November 24, 2014