Nav1.1

Sodium channel, voltage gated, type I alpha subunit
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1byy​
Identifiers
Symbols	SCN1A ; EIEE6; FEB3; FEB3A; FHM3; GEFSP2; HBSCI; NAC1; Nav1.1; SCN1; SMEI
External IDs	OMIM: 182389 MGI: 98246 HomoloGene: 21375 IUPHAR: 578 ChEMBL: 1845 GeneCards: SCN1A Gene
Gene ontology Molecular function • voltage-gated sodium channel activity Cellular component • voltage-gated sodium channel complex • plasma membrane • intercalated disc • Z disc • T-tubule • node of Ranvier • neuronal cell body • axon initial segment Biological process • positive regulation of defense response to virus by host • sodium ion transport • adult walking behavior • neuronal action potential propagation • neuronal action potential • regulation of ion transmembrane transport • sodium ion transmembrane transport • neuromuscular process controlling posture • membrane depolarization during action potential Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6323	20265
Ensembl	ENSG00000144285	ENSMUSG00000064329
UniProt	P35498	A2APX6
RefSeq (mRNA)	NM_001165963	NM_018733
RefSeq (protein)	NP_001159435	NP_061203
Location (UCSC)	Chr 2: 165.99 – 166.13 Mb	Chr 2: 66.27 – 66.44 Mb
PubMed search

Na_v1.1, also known as the sodium channel, voltage-gated, type I, alpha subunit (SCN1A), is a protein which in humans is encoded by the SCN1A gene.^[1][2][3][4]

Function

The vertebrate sodium channel is a voltage-gated ion channel essential for the generation and propagation of action potentials, chiefly in nerve and muscle. Voltage-sensitive sodium channels are heteromeric complexes consisting of a large central pore-forming glycosylated alpha subunit and 2 smaller auxiliary beta subunits. Functional studies have indicated that the transmembrane alpha subunit of the brain sodium channels is sufficient for expression of functional sodium channels.^[5][6] Brain sodium channel alpha subunits form a gene subfamily with several structurally distinct isoforms clustering on chromosome 2q24, types I, II (Na_v1.2), and III (Na_v1.3). There are also several distinct sodium channel alpha subunit isoforms in skeletal and cardiac muscle (Na_v1.4^[7] and Na_v1.5,^[8] respectively).

Clinical significance

Mutations in the SCN1A gene cause inherited febrile seizures and GEFS+, type 2.^{[9][10][11][12]}

Patent controversy

On 29 November 2008, The Sydney Morning Herald reported the first evidence of private intellectual property rights over human DNA^[13] having adversely affected medical care. The Melbourne company Genetic Technologies (GTG) controls rights to the gene, and requires royalties for tests on the gene, which can help identify Dravet syndrome. Doctors on the Children's Hospital in Westmead, Australia have told journalists that they would test 50% more infants for the gene, if they could conduct the test on site.

Interactions

Na_v1.1 has been shown to interact with syntrophin, alpha 1.^[14]

See also

• Sodium channel

References

1. "Entrez Gene: SCN1A sodium channel, voltage-gated, type I, alpha subunit".
2. Malo MS, Blanchard BJ, Andresen JM, Srivastava K, Chen XN, Li X, Jabs EW, Korenberg JR, Ingram VM (1994). "Localization of a putative human brain sodium channel gene (SCN1A) to chromosome band 2q24". Cytogenetics and Cell Genetics 67 (3): 178–86. doi:10.1159/000133818. PMID 8062593.
3. Ito M, Nagafuji H, Okazawa H, Yamakawa K, Sugawara T, Mazaki-Miyazaki E, Hirose S, Fukuma G, Mitsudome A, Wada K, Kaneko S (Jan 2002). "Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A". Epilepsy Research 48 (1-2): 15–23. doi:10.1016/S0920-1211(01)00313-8. PMID 11823106.
4. Catterall WA, Goldin AL, Waxman SG (Dec 2005). "International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels". Pharmacological Reviews 57 (4): 397–409. doi:10.1124/pr.57.4.4. PMID 16382098.
5. Goldin AL, Snutch T, Lübbert H, Dowsett A, Marshall J, Auld V, Downey W, Fritz LC, Lester HA, Dunn R (Oct 1986). "Messenger RNA coding for only the alpha subunit of the rat brain Na channel is sufficient for expression of functional channels in Xenopus oocytes". Proceedings of the National Academy of Sciences of the United States of America 83 (19): 7503–7. doi:10.1073/pnas.83.19.7503. PMC 386747. PMID 2429308.
6. Isom LL (Jan 2002). "The role of sodium channels in cell adhesion". Frontiers in Bioscience 7: 12–23. doi:10.2741/isom. PMID 11779698.
7. George AL, Komisarof J, Kallen RG, Barchi RL (Feb 1992). "Primary structure of the adult human skeletal muscle voltage-dependent sodium channel". Annals of Neurology 31 (2): 131–7. doi:10.1002/ana.410310203. PMID 1315496.
8. Gellens ME, George AL, Chen LQ, Chahine M, Horn R, Barchi RL, Kallen RG (Jan 1992). "Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel". Proceedings of the National Academy of Sciences of the United States of America 89 (2): 554–8. doi:10.1073/pnas.89.2.554. PMC 48277. PMID 1309946.
9. Escayg A, MacDonald BT, Meisler MH, Baulac S, Huberfeld G, An-Gourfinkel I, Brice A, LeGuern E, Moulard B, Chaigne D, Buresi C, Malafosse A (Apr 2000). "Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2". Nature Genetics 24 (4): 343–5. doi:10.1038/74159. PMID 10742094.
10. Spampanato J, Escayg A, Meisler MH, Goldin AL (Oct 2001). "Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2". The Journal of Neuroscience 21 (19): 7481–90. PMID 11567038.
11. Nabbout R, Gennaro E, Dalla Bernardina B, Dulac O, Madia F, Bertini E, Capovilla G, Chiron C, Cristofori G, Elia M, Fontana E, Gaggero R, Granata T, Guerrini R, Loi M, La Selva L, Lispi ML, Matricardi A, Romeo A, Tzolas V, Valseriati D, Veggiotti P, Vigevano F, Vallée L, Dagna Bricarelli F, Bianchi A, Zara F (Jun 2003). "Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy". Neurology 60 (12): 1961–7. doi:10.1212/01.wnl.0000069463.41870.2f. PMID 12821740.
12. Lossin C. "SCN1A infobase". Retrieved 2009-10-30. compilation of genetic variations in the SCN1A gene that alter the expression or function of Nav1.1
13. Robotham J (29 November 2008). "Sick babies denied treatment in DNA row –". National News. Sidney Morning Herald – smh.com.au. Retrieved 2008-12-03.
14. Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC (Jan 1998). "Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins". The Journal of Neuroscience 18 (1): 128–37. PMID 9412493.

Further reading

• Lerche H, Jurkat-Rott K, Lehmann-Horn F (2001). "Ion channels and epilepsy". American Journal of Medical Genetics 106 (2): 146–59. doi:10.1002/ajmg.1582. PMID 11579435.
• Isom LL (Jan 2002). "The role of sodium channels in cell adhesion". Frontiers in Bioscience 7: 12–23. doi:10.2741/isom. PMID 11779698.
• Kanai K, Hirose S, Oguni H, Fukuma G, Shirasaka Y, Miyajima T, Wada K, Iwasa H, Yasumoto S, Matsuo M, Ito M, Mitsudome A, Kaneko S (Jul 2004). "Effect of localization of missense mutations in SCN1A on epilepsy phenotype severity". Neurology 63 (2): 329–34. doi:10.1212/01.wnl.0000129829.31179.5b. PMID 15277629.
• Oguni H, Hayashi K, Osawa M, Awaya Y, Fukuyama Y, Fukuma G, Hirose S, Mitsudome A, Kaneko S (2004). "Severe myoclonic epilepsy in infancy: clinical analysis and relation to SCN1A mutations in a Japanese cohort". Advances in Neurology 95: 103–17. PMID 15508916.
• Mulley JC, Scheffer IE, Petrou S, Dibbens LM, Berkovic SF, Harkin LA (Jun 2005). "SCN1A mutations and epilepsy". Human Mutation 25 (6): 535–42. doi:10.1002/humu.20178. PMID 15880351.
• Catterall WA, Goldin AL, Waxman SG (Dec 2005). "International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels". Pharmacological Reviews 57 (4): 397–409. doi:10.1124/pr.57.4.4. PMID 16382098.
• Lu CM, Han J, Rado TA, Brown GB (May 1992). "Differential expression of two sodium channel subtypes in human brain". FEBS Letters 303 (1): 53–8. doi:10.1016/0014-5793(92)80476-W. PMID 1317301.
• Goldin AL, Snutch T, Lübbert H, Dowsett A, Marshall J, Auld V, Downey W, Fritz LC, Lester HA, Dunn R (Oct 1986). "Messenger RNA coding for only the alpha subunit of the rat brain Na channel is sufficient for expression of functional channels in Xenopus oocytes". Proceedings of the National Academy of Sciences of the United States of America 83 (19): 7503–7. doi:10.1073/pnas.83.19.7503. PMC 386747. PMID 2429308.
• Malo MS, Blanchard BJ, Andresen JM, Srivastava K, Chen XN, Li X, Jabs EW, Korenberg JR, Ingram VM (1994). "Localization of a putative human brain sodium channel gene (SCN1A) to chromosome band 2q24". Cytogenetics and Cell Genetics 67 (3): 178–86. doi:10.1159/000133818. PMID 8062593.
• Peiffer A, Thompson J, Charlier C, Otterud B, Varvil T, Pappas C, Barnitz C, Gruenthal K, Kuhn R, Leppert M (Oct 1999). "A locus for febrile seizures (FEB3) maps to chromosome 2q23-24". Annals of Neurology 46 (4): 671–8. doi:10.1002/1531-8249(199910)46:4<671::AID-ANA20>3.0.CO;2-5. PMID 10514109.
• Wallace RH, Scheffer IE, Barnett S, Richards M, Dibbens L, Desai RR, Lerman-Sagie T, Lev D, Mazarib A, Brand N, Ben-Zeev B, Goikhman I, Singh R, Kremmidiotis G, Gardner A, Sutherland GR, George AL, Mulley JC, Berkovic SF (Apr 2001). "Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus". American Journal of Human Genetics 68 (4): 859–65. doi:10.1086/319516. PMC 1275639. PMID 11254444.
• Escayg A, Heils A, MacDonald BT, Haug K, Sander T, Meisler MH (Apr 2001). "A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus--and prevalence of variants in patients with epilepsy". American Journal of Human Genetics 68 (4): 866–73. doi:10.1086/319524. PMC 1275640. PMID 11254445.
• Whitaker WR, Faull RL, Waldvogel HJ, Plumpton CJ, Emson PC, Clare JJ (Mar 2001). "Comparative distribution of voltage-gated sodium channel proteins in human brain". Brain Research. Molecular Brain Research 88 (1-2): 37–53. doi:10.1016/S0169-328X(00)00289-8. PMID 11295230.
• Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P (Jun 2001). "De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy". American Journal of Human Genetics 68 (6): 1327–32. doi:10.1086/320609. PMC 1226119. PMID 11359211.
• Sugawara T, Mazaki-Miyazaki E, Ito M, Nagafuji H, Fukuma G, Mitsudome A, Wada K, Kaneko S, Hirose S, Yamakawa K (Aug 2001). "Nav1.1 mutations cause febrile seizures associated with afebrile partial seizures". Neurology 57 (4): 703–5. doi:10.1212/wnl.57.4.703. PMID 11524484.
• Abou-Khalil B, Ge Q, Desai R, Ryther R, Bazyk A, Bailey R, Haines JL, Sutcliffe JS, George AL (Dec 2001). "Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation". Neurology 57 (12): 2265–72. doi:10.1212/wnl.57.12.2265. PMID 11756608.
• Ito M, Nagafuji H, Okazawa H, Yamakawa K, Sugawara T, Mazaki-Miyazaki E, Hirose S, Fukuma G, Mitsudome A, Wada K, Kaneko S (Jan 2002). "Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A". Epilepsy Research 48 (1-2): 15–23. doi:10.1016/S0920-1211(01)00313-8. PMID 11823106.

External links

• GeneReviews/NCBI/NIH/UW entry on Familial Hemiplegic Migraine
• GeneReviews/NCBI/NIH/UW entry on SCN1A-Related Seizure Disorders
• SCN1A protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.