SCN1A
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Sodium channel protein type 1 subunit alpha (SCN1A), is a protein which in humans is encoded by the SCN1A gene.[5][6][7][8]
Gene location
The SCN1A gene is located on chromosome 2 of humans, and is made up of 26 exons spanning a total length of 6030 nucleotide base pairs.[9][10] Alternative splicing of exon 5 gives rise to two alternate exons.[11] The promoter has been identified 2.5 kilobase pairs upstream of the transcription start site, and the 5'- untranslated exons may enhance expression of the SCN1A gene in SH-SY5Y cells, a human cell line derived from a neuroblastoma.[12]
Function
The vertebrate
The SCN1A gene codes for the
Subtle differences in voltage-gated sodium ion channels can have devastating physiological effects and underlie abnormal neurological functioning.[20][21] Mutations to the SCN1A gene most often result in different forms of seizure disorders, the most common forms of seizure disorders are Dravet Syndrome (DS), Intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC), and severe myoclonic epilepsy borderline (SMEB).[18] Clinically, 70-80% of patients with DS have identified mutations specific to the SCN1A gene, which are caused by de novo heterozygous mutations of the SCN1A gene.[22] There are currently two databases on SCN1A mutations, Infobase and the SCN1A variant database Archived 22 July 2019 at the Wayback Machine.
Mice with knock-in SCN1A mutations, who are model organisms for DS quickly develop seizures, indicative of a significant reduction in the function of NaV1.1.[10] It has been hypothesized that reduced sodium currents due to NaV1.1 mutations may cause hypoexcitability in GABAergic inhibitory interneurons leading to epilepsy.[12] Mice in both the homozygous and heterozygous states develop the seizure phenotype and ataxia. Though homozygous mice die on average during the second to third week of life and approximately 50% of heterozygous null mice survive into adulthood.[10][12][23]
Clinical significance
Mutations in the SCN1A gene cause inherited febrile seizures and GEFS+, type 2.[24][25][26][27]
Patent controversy
On 29 November 2008, The
Interactions
Nav1.1 has been shown to
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000144285 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000064329 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: SCN1A sodium channel, voltage-gated, type I, alpha subunit".
- PMID 8062593.
- S2CID 25555020.
- S2CID 7332624.
- ^ PMID 20351042.
- ^ PMID 17537961.
- PMID 15805193.
- ^ S2CID 33673297.
- PMID 2429308.
- S2CID 37892568.
- PMID 1309946.
- doi:10.1038/74159
- ^
- ^ Kohrman, D. C., Smith, M. R., Goldin, A. L., Harris, J., & Meisler, M. H. (1996). A Missense Mutation in the Sodium Channel Scn8a Is Responsible for Cerebellar Ataxia in the Mouse Mutant jolting. Journal of Neuroscience, 16(19), 5993–5999.
- ^ Claes, L., Del-Favero, J., Ceulemans, B., Lagae, L., Van Broeckhoven, C., & De Jonghe, P. (2001). De Novo Mutations in the Sodium-Channel Gene SCN1A Cause Severe Myoclonic Epilepsy of Infancy. American Journal of Human Genetics, 68(6), 1327–1332.
- doi:10.1038/nn1754
- S2CID 29543172.
- PMID 11567038.
- S2CID 604240.
- ^ Lossin C. "SCN1A infobase". Retrieved 30 October 2009.
compilation of genetic variations in the SCN1A gene that alter the expression or function of Nav1.1
- ^ Robotham J (29 November 2008). "Sick babies denied treatment in DNA row –". National News. Sidney Morning Herald – smh.com.au. Retrieved 3 December 2008.
- 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. PMID 11579435.
- Isom LL (January 2002). "The role of sodium channels in cell adhesion". Frontiers in Bioscience. 7 (1–3): 12–23. PMID 11779698.
- Kanai K, Hirose S, Oguni H, Fukuma G, Shirasaka Y, Miyajima T, et al. (July 2004). "Effect of localization of missense mutations in SCN1A on epilepsy phenotype severity". Neurology. 63 (2): 329–34. S2CID 36070893.
- Oguni H, Hayashi K, Osawa M, Awaya Y, Fukuyama Y, Fukuma G, et al. (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 (June 2005). "SCN1A mutations and epilepsy". Human Mutation. 25 (6): 535–42. S2CID 19148287.
- Catterall WA, Goldin AL, Waxman SG (December 2005). "International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels". Pharmacological Reviews. 57 (4): 397–409. S2CID 7332624.
- 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. S2CID 29330026.
- Goldin AL, Snutch T, Lübbert H, Dowsett A, Marshall J, Auld V, et al. (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" (PDF). Proceedings of the National Academy of Sciences of the United States of America. 83 (19): 7503–7. PMID 2429308.
- Malo MS, Blanchard BJ, Andresen JM, Srivastava K, Chen XN, Li X, et al. (1994). "Localization of a putative human brain sodium channel gene (SCN1A) to chromosome band 2q24". Cytogenetics and Cell Genetics. 67 (3): 178–86. PMID 8062593.
- Peiffer A, Thompson J, Charlier C, Otterud B, Varvil T, Pappas C, et al. (October 1999). "A locus for febrile seizures (FEB3) maps to chromosome 2q23-24". Annals of Neurology. 46 (4): 671–8. S2CID 33638988.
- Wallace RH, Scheffer IE, Barnett S, Richards M, Dibbens L, Desai RR, et al. (April 2001). "Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus". American Journal of Human Genetics. 68 (4): 859–65. PMID 11254444.
- Escayg A, Heils A, MacDonald BT, Haug K, Sander T, Meisler MH (April 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. PMID 11254445.
- Whitaker WR, Faull RL, Waldvogel HJ, Plumpton CJ, Emson PC, Clare JJ (March 2001). "Comparative distribution of voltage-gated sodium channel proteins in human brain". Brain Research. Molecular Brain Research. 88 (1–2): 37–53. PMID 11295230.
- Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P (June 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. PMID 11359211.
- Sugawara T, Mazaki-Miyazaki E, Ito M, Nagafuji H, Fukuma G, Mitsudome A, et al. (August 2001). "Nav1.1 mutations cause febrile seizures associated with afebrile partial seizures". Neurology. 57 (4): 703–5. S2CID 45138036.
- Abou-Khalil B, Ge Q, Desai R, Ryther R, Bazyk A, Bailey R, et al. (December 2001). "Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation". Neurology. 57 (12): 2265–72. S2CID 26448714.
- Ito M, Nagafuji H, Okazawa H, Yamakawa K, Sugawara T, Mazaki-Miyazaki E, et al. (January 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. S2CID 25555020.
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 U.S. National Library of Medicine Medical Subject Headings (MeSH)
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.