Nav1.1

SCN1A
Identifiers
AliasesSCN1A, EIEE6, FEB3, FEB3A, FHM3, GEFSP2, HBSCI, NAC1, Nav1.1, SCN1, SMEI, sodium voltage-gated channel alpha subunit 1
External IDsMGI: 98246 HomoloGene: 21375 GeneCards: SCN1A
Gene location (Human)
Chr.Chromosome 2 (human)[1]
Band2q24.3Start165,984,641 bp[1]
End166,149,214 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

6323

20265

Ensembl

ENSG00000144285

ENSMUSG00000064329

UniProt

P35498

A2APX8

RefSeq (mRNA)

NM_018733
NM_001313997

RefSeq (protein)

NP_001300926
NP_061203

Location (UCSC)Chr 2: 165.98 – 166.15 MbChr 2: 66.27 – 66.44 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Nav1.1, 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.[5][6][7][8]

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.[9] Brain sodium channel alpha subunits form a gene subfamily with several structurally distinct isoforms clustering on chromosome 2q24, types I, II (Nav1.2), and III (Nav1.3). There are also several distinct sodium channel alpha subunit isoforms in skeletal and cardiac muscle (Nav1.4[10] and Nav1.5,[11] respectively).

Clinical significance

Mutations in the SCN1A gene cause inherited febrile seizures and GEFS+, type 2.[12][13][14][15]

Patent controversy

On 29 November 2008, The Sydney Morning Herald reported the first evidence of private intellectual property rights over human DNA[16] 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

Nav1.1 has been shown to interact with syntrophin, alpha 1.[17]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000144285 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000064329 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ "Entrez Gene: SCN1A sodium channel, voltage-gated, type I, alpha subunit".
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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
  16. ↑ Robotham J (29 November 2008). "Sick babies denied treatment in DNA row –". National News. Sidney Morning Herald – smh.com.au. Retrieved 2008-12-03.
  17. ↑ 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.

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