Sodium channel, voltage-gated, type I, alpha subunit

Solution structure of the rat Nav1.1 sodium channel inactivation gate.[1] This gate (25 amino acids residues in length) is a small portion of the entire sodium channel (which contains a a total of 2009 amino acids). The inactivation gate is located between repeat domains III and IV of the sodium channel protein.
Symbols SCN1A; FEB3; GEFSP2; HBSCI; NAC1; Nav1.1; SCN1; SMEI
External IDs OMIM182389 MGI98246 HomoloGene21375 IUPHAR: Nav1.1 GeneCards: SCN1A Gene
RNA expression pattern
PBB GE SCN1A 210383 at tn.png
More reference expression data
Species Human Mouse
Entrez 6323 20265
Ensembl ENSG00000144285 ENSMUSG00000064329
UniProt P35498 n/a
RefSeq (mRNA) NM_006920 XM_001001733
RefSeq (protein) NP_008851 XP_001001733
Location (UCSC) Chr 2:
166.55 – 166.64 Mb
Chr 2:
66.07 – 66.12 Mb
PubMed search [1] [2]

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.[2][3][4][5]



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.[6][7] 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[8] and Nav1.5,[9] respectively).

Clinical significance

Mutations in the SCNA1 gene cause inherited febrile seizures and GEFS+, type 2.[10][11][12][13]

Patent controversy

On November 29th 2008, The Sydney Morning Herald reported the first evidence of private intellectual property rights over human DNA[14] 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.


Nav1.1 has been shown to interact with syntrophin, alpha 1.[15]

See also


  1. ^ PDB 1byy; Rohl CA, Boeckman FA, Baker C, Scheuer T, Catterall WA, Klevit RE (January 1999). "Solution structure of the sodium channel inactivation gate". Biochemistry 38 (3): 855–61. doi:10.1021/bi9823380. PMID 9893979. 
  2. ^ "Entrez Gene: SCN1A sodium channel, voltage-gated, type I, alpha subunit". 
  3. ^ 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". Cytogenet. Cell Genet. 67 (3): 178–86. doi:10.1159/000133818. PMID 8062593. 
  4. ^ Ito M, Nagafuji H, Okazawa H, Yamakawa K, Sugawara T, Mazaki-Miyazaki E, Hirose S, Fukuma G, Mitsudome A, Wada K, Kaneko S (January 2002). "Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A". Epilepsy Res. 48 (1–2): 15–23. doi:10.1016/S0920-1211(01)00313-8. PMID 11823106. 
  5. ^ Catterall WA, Goldin AL, Waxman SG (December 2005). "International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels". Pharmacol. Rev. 57 (4): 397–409. doi:10.1124/pr.57.4.4. PMID 16382098. 
  6. ^ Goldin AL, Snutch T, Lübbert H, Dowsett A, Marshall J, Auld V, Downey W, Fritz LC, Lester HA, Dunn R (October 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". Proc. Natl. Acad. Sci. U.S.A. 83 (19): 7503–7. doi:10.1073/pnas.83.19.7503. PMC 386747. PMID 2429308. 
  7. ^ Isom LL (January 2002). "The role of sodium channels in cell adhesion". Front. Biosci. 7: 12–23. doi:10.2741/isom. PMID 11779698. 
  8. ^ George AL, Komisarof J, Kallen RG, Barchi RL (February 1992). "Primary structure of the adult human skeletal muscle voltage-dependent sodium channel". Ann. Neurol. 31 (2): 131–7. doi:10.1002/ana.410310203. PMID 1315496. 
  9. ^ Gellens ME, George AL, Chen LQ, et al. (January 1992). "Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel". Proc. Natl. Acad. Sci. U.S.A. 89 (2): 554–8. doi:10.1073/pnas.89.2.554. PMC 48277. PMID 1309946. 
  10. ^ 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 (April 2000). "Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2". Nat. Genet. 24 (4): 343–5. doi:10.1038/74159. PMID 10742094. 
  11. ^ Spampanato J, Escayg A, Meisler MH, Goldin AL (October 2001). "Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2". J. Neurosci. 21 (19): 7481–90. PMID 11567038. 
  12. ^ 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 (June 2003). "Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy". Neurology 60 (12): 1961–7. PMID 12821740. 
  13. ^ 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" 
  14. ^ Robotham J (2008-11-29). "Sick babies denied treatment in DNA row -". National News. Sidney Morning Herald - Retrieved 2008-12-03. 
  15. ^ Gee, S H; Madhavan R, Levinson S R, Caldwell J H, Sealock R, Froehner S C (Jan. 1998). "Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins". J. Neurosci. (UNITED STATES) 18 (1): 128–37. ISSN 0270-6474. PMID 9412493. 

Further reading

External links