SCN1A

SCN1A
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	7DTD
Identifikatori
Aliasi	SCN1A
Vanjski ID-jevi	OMIM: 182389 MGI: 98246 HomoloGene: 21375 GeneCards: SCN1A
Lokacija gena (čovjek)
Hrom.	Hromosom 2 (čovjek)
Kraj	166,149,214 bp
Lokacija gena (miš)
Hrom.	Hromosom 2 (miš)
Kraj	66,271,184 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• sodium channel activity; • voltage-gated ion channel activity; • ion channel activity; • voltage-gated sodium channel activity;
Ćelijska komponenta	• voltage-gated sodium channel complex; • integral component of membrane; • membrana; • nukleoplazma; • ćelijska membrana; • nuclear body; • Interkalirani disk; • Z disc; • T-tubule; • Akson; • Ranvijerov čvor; • sodium channel complex; • neuronal cell body; • axon initial segment;
Biološki proces	• membrane depolarization during action potential; • sodium ion transmembrane transport; • regulation of ion transmembrane transport; • ion transport; • transmembrane transport; • ion transmembrane transport; • sodium ion transport; • cardiac muscle cell action potential involved in contraction; • Akcijski potencijal; • adult walking behavior; • neuronal action potential propagation; • neuronal action potential; • regulation of membrane potential; • neuromuscular process controlling posture; • detection of mechanical stimulus involved in sensory perception of pain;
	Izvori:Amigo / QuickGO
Ortolozi
	6323
	20265
	ENSG00000144285
	ENSMUSG00000064329
	P35498
	A2APX8
NM_001165963; NM_001165964; NM_001202435; NM_006920; NM_001353948;
	NM_001353949; NM_001353950; NM_001353951; NM_001353952; NM_001353954; NM_001353955; NM_001353957; NM_001353958; NM_001353960; NM_001353961
	NM_018733; NM_001313997
NP_001159435; NP_001159436; NP_001189364; NP_008851; NP_001340877;
	NP_001340878; NP_001340879; NP_001340880; NP_001340881; NP_001340883; NP_001340884; NP_001340886; NP_001340887; NP_001340889; NP_001340890
	NP_001300926; NP_061203
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Podjedinica alfa proteinskog tipa 1 natrijskog kanala (SCN1A), jest protein koji je kod ljudi kodiran genom SCN1A sa hromosoma 2.^[5]^[6]^[7]^[8]

Lokacija gena[uredi | uredi izvor]

Kodljudi, gen SCN1A nalazi se na hromosomu 2, i sastoji se od 26 egzona koji obuhvataju ukupnu dužinu od 6.030 parova nukleotidnih baza (bp).^[9]^[10] Alternativna prerada egzona 5 dovodi do dva alternativna egzona.^[11] Promotor je identificiran 2,5 kilobaznih parova (kb) uzvodno od mjesta početka transkripcije, a 5'-netranslirani egzoni mogu poboljšati ekspresiju gena SCN1A u SH-SY5Y ćelijama, ljudske ćelijske linije izvedenoj od neuroblastoma.^[12]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 2.009 aminokiselina, a molekulska težina 228.972 Da.^[5]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MEQTVLVPPG	PDSFNFFTRE	SLAAIERRIA	EEKAKNPKPD	KKDDDENGPK
PNSDLEAGKN	LPFIYGDIPP	EMVSEPLEDL	DPYYINKKTF	IVLNKGKAIF
RFSATSALYI	LTPFNPLRKI	AIKILVHSLF	SMLIMCTILT	NCVFMTMSNP
PDWTKNVEYT	FTGIYTFESL	IKIIARGFCL	EDFTFLRDPW	NWLDFTVITF
AYVTEFVDLG	NVSALRTFRV	LRALKTISVI	PGLKTIVGAL	IQSVKKLSDV
MILTVFCLSV	FALIGLQLFM	GNLRNKCIQW	PPTNASLEEH	SIEKNITVNY
NGTLINETVF	EFDWKSYIQD	SRYHYFLEGF	LDALLCGNSS	DAGQCPEGYM
CVKAGRNPNY	GYTSFDTFSW	AFLSLFRLMT	QDFWENLYQL	TLRAAGKTYM
IFFVLVIFLG	SFYLINLILA	VVAMAYEEQN	QATLEEAEQK	EAEFQQMIEQ
LKKQQEAAQQ	AATATASEHS	REPSAAGRLS	DSSSEASKLS	SKSAKERRNR
RKKRKQKEQS	GGEEKDEDEF	QKSESEDSIR	RKGFRFSIEG	NRLTYEKRYS
SPHQSLLSIR	GSLFSPRRNS	RTSLFSFRGR	AKDVGSENDF	ADDEHSTFED
NESRRDSLFV	PRRHGERRNS	NLSQTSRSSR	MLAVFPANGK	MHSTVDCNGV
VSLVGGPSVP	TSPVGQLLPE	VIIDKPATDD	NGTTTETEMR	KRRSSSFHVS
MDFLEDPSQR	QRAMSIASIL	TNTVEELEES	RQKCPPCWYK	FSNIFLIWDC
SPYWLKVKHV	VNLVVMDPFV	DLAITICIVL	NTLFMAMEHY	PMTDHFNNVL
TVGNLVFTGI	FTAEMFLKII	AMDPYYYFQE	GWNIFDGFIV	TLSLVELGLA
NVEGLSVLRS	FRLLRVFKLA	KSWPTLNMLI	KIIGNSVGAL	GNLTLVLAII
VFIFAVVGMQ	LFGKSYKDCV	CKIASDCQLP	RWHMNDFFHS	FLIVFRVLCG
EWIETMWDCM	EVAGQAMCLT	VFMMVMVIGN	LVVLNLFLAL	LLSSFSADNL
AATDDDNEMN	NLQIAVDRMH	KGVAYVKRKI	YEFIQQSFIR	KQKILDEIKP
LDDLNNKKDS	CMSNHTAEIG	KDLDYLKDVN	GTTSGIGTGS	SVEKYIIDES
DYMSFINNPS	LTVTVPIAVG	ESDFENLNTE	DFSSESDLEE	SKEKLNESSS
SSEGSTVDIG	APVEEQPVVE	PEETLEPEAC	FTEGCVQRFK	CCQINVEEGR
GKQWWNLRRT	CFRIVEHNWF	ETFIVFMILL	SSGALAFEDI	YIDQRKTIKT
MLEYADKVFT	YIFILEMLLK	WVAYGYQTYF	TNAWCWLDFL	IVDVSLVSLT
ANALGYSELG	AIKSLRTLRA	LRPLRALSRF	EGMRVVVNAL	LGAIPSIMNV
LLVCLIFWLI	FSIMGVNLFA	GKFYHCINTT	TGDRFDIEDV	NNHTDCLKLI
ERNETARWKN	VKVNFDNVGF	GYLSLLQVAT	FKGWMDIMYA	AVDSRNVELQ
PKYEESLYMY	LYFVIFIIFG	SFFTLNLFIG	VIIDNFNQQK	KKFGGQDIFM
TEEQKKYYNA	MKKLGSKKPQ	KPIPRPGNKF	QGMVFDFVTR	QVFDISIMIL
ICLNMVTMMV	ETDDQSEYVT	TILSRINLVF	IVLFTGECVL	KLISLRHYYF
TIGWNIFDFV	VVILSIVGMF	LAELIEKYFV	SPTLFRVIRL	ARIGRILRLI
KGAKGIRTLL	FALMMSLPAL	FNIGLLLFLV	MFIYAIFGMS	NFAYVKREVG
IDDMFNFETF	GNSMICLFQI	TTSAGWDGLL	APILNSKPPD	CDPNKVNPGS
SVKGDCGNPS	VGIFFFVSYI	IISFLVVVNM	YIAVILENFS	VATEESAEPL
SEDDFEMFYE	VWEKFDPDAT	QFMEFEKLSQ	FAAALEPPLN	LPQPNKLQLI
AMDLPMVSGD	RIHCLDILFA	FTKRVLGESG	EMDALRIQME	ERFMASNPSK
VSYQPITTTL	KRKQEEVSAV	IIQRAYRRHL	LKRTVKQASF	TYNKNKIKGG
ANLLIKEDMI	IDRINENSIT	EKTDLTMSTA	ACPPSYDRVT	KPIVEKHEQE
GKDEKAKGK

Funkcija[uredi | uredi izvor]

Kičmenjački natrijski kanal je naponski-ovisni ionki kanal, neophodan za stvaranje i širenje akcijskih potencijala, uglavnom u nervima i mišićima. Natrijski kanali osetljivi na napon su heteromerni kompleksi koji se sastoje od velike centralne glikozilovane alfa podjedinice koja stvara pore i dvije manje pomoćne beta podjedinice. Funkcionalne studije su pokazale da je transmembranska alfa podjedinica moždanih natrijevih kanala dovoljna za ekspresiju funkcionalnih natrijevih kanala.^[13] Alfa podjedinice moždanih natrijskih kanala mozga formiraju potporodicu gena sa nekoliko strukturno različitih izoformi grupisanih na hromosomskoj ref+giji 2q24, tipovi I, II (Na_v1.2) i III (Na_v1.3). Također postoji nekoliko različitih izoformi alfa podjedinica natrijevih kanala u skeletnim i srčanim mišićima (Na_v1.4^[14] i Na_v1.5).^[15]

SCN1A gen kodira alfa podjedinicu napo-ovisnog natrijevog ionskog kanala, što ga čini članom deset paralognih porodica gena koje kodiraju naponski natrijev transmembranski protein Na_V1.1. Unutar porodice gena koji kodiraju druge dijelove naponski-oviksnihnatrijskih kanala, mutacije SCN1A su prve identificirane, jer su mutacije ovog gena uzrokovale epilepsiju i febrilne napade.^[16] Odista, gen SCN1A je jedan od najčešće mutiranih gena u ljudskom genomu koji je povezan s epilepsijom, što mu je dalo titulu „gena super krivca“.^[17] Postoji 900 različitih mutacija prijavljenih za gen SCN1A, otprilike polovina prijavljenih mutacija su skraćivanja koja rezultiraju bez sinteze proteina.^[18]^[19] Preostala polovina mutacija su misens mutacije, za koje se predviđa da će ili uzrokovati gubitsk funkcije ili dobitak funkcija, iako je vrlo malo njih testirano na funkcionalnost u laboratoriji.^[9]

Suptilne razlike u naponskim kanalima natrijevih iona, mogu imati razorne fiziološke efekte i biti u osnovi abnormalnog neurološkog funkcionisanja.^[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] Klinički, 70-80% pacijenata sa DS je identifikovano s mutacijama specifičnim za gen SCN1A, koje su uzrokovane de novo heterozigotnim mutacijama gena SCN1A.^[22] Do sada postoje dvije baze podataka o SCN1A mutacijama, Infobase i SCN1A varijantna baza podataka Arhivirano 22. 7. 2019. na Wayback Machine.

Miševi s nok-in SCN1A mutacijama, koji su modelni organizmi za DS, brzo razvijaju napade, što ukazuje na značajno smanjenje funkcije Na_V1.1.^[10] Pretpostavljeno je da smanjene struje natrija zbog Na_V1.1 mutacija mogu uzrokovati hipoekscitabilnost u GABA inhibitornim interneuronima, što dovodi do epilepsije.^[12] Miševi i u homozigotnom i u heterozigotnolm stanju razvijaju fenotip napada i ataksiju. Iako homozigotni miševi umiru u prosjeku tokom druge do treće sedmice života, a otprilike 50% heterozigotnih nul-miševa preživi u odrasloj dobi.^[10]^[12]^[23]

Klinički značaj[uredi | uredi izvor]

Mutacije u genu SCN1A uzrokuju nasljedne febrilne napade i GEFS+, tip 2.^[24]^[25]^[26]^[27]

Interakcije[uredi | uredi izvor]

Pokazalo se da Na_v1.1 ima reakcije sa sintropinom alfa 1.^[28]

Također pogledajte[uredi | uredi izvor]

Natrijski kanal

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000144285 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000064329 - Ensembl, maj 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.
^ ^a ^b "Entrez Gene: SCN1A sodium channel, voltage-gated, type I, alpha subunit".
^ 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. doi:10.1159/000133818. PMID 8062593.
^ Ito M, Nagafuji H, Okazawa H, Yamakawa K, Sugawara T, Mazaki-Miyazaki E, et al. (januar 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. S2CID 25555020.
^ Catterall WA, Goldin AL, Waxman SG (decembar 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. S2CID 7332624.
^ ^a ^b Meisler MH, O'Brien JE, Sharkey LM (juni 2010). "Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects". The Journal of Physiology. 588 (Pt 11): 1841–8. doi:10.1113/jphysiol.2010.188482. PMC 2901972. PMID 20351042.
^ ^a ^b ^c Ogiwara I, Miyamoto H, Morita N, Atapour N, Mazaki E, Inoue I, et al. (maj 2007). "Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation". The Journal of Neuroscience. 27 (22): 5903–14. doi:10.1523/JNEUROSCI.5270-06.2007. PMC 6672241. PMID 17537961.
^ Tate SK, Depondt C, Sisodiya SM, Cavalleri GL, Schorge S, Soranzo N, et al. (april 2005). "Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin". Proceedings of the National Academy of Sciences of the United States of America. 102 (15): 5507–12. Bibcode:2005PNAS..102.5507T. doi:10.1073/pnas.0407346102. PMC 556232. PMID 15805193.
^ ^a ^b ^c Long YS, Zhao QH, Su T, Cai YL, Zeng Y, Shi YW, et al. (novembar 2008). "Identification of the promoter region and the 5'-untranslated exons of the human voltage-gated sodium channel Nav1.1 gene (SCN1A) and enhancement of gene expression by the 5'-untranslated exons". Journal of Neuroscience Research. 86 (15): 3375–81. doi:10.1002/jnr.21790. PMID 18655196. S2CID 33673297.
^ Goldin AL, Snutch T, Lübbert H, Dowsett A, Marshall J, Auld V, et al. (oktobar 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. Bibcode:1986PNAS...83.7503G. doi:10.1073/pnas.83.19.7503. PMC 386747. PMID 2429308.
^ George AL, Komisarof J, Kallen RG, Barchi RL (februar 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. S2CID 37892568.
^ Gellens ME, George AL, Chen LQ, Chahine M, Horn R, Barchi RL, Kallen RG (januar 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. Bibcode:1992PNAS...89..554G. doi:10.1073/pnas.89.2.554. PMC 48277. PMID 1309946.
^ Escayg, A., MacDonald, B. T., Meisler, M. H., Baulac, S., Huberfeld, G., An-Gourfinkel, I., … Malafosse, A. (2000). Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2. Nature Genetics, 24(4), 343–345. https://doi.org/10.1038/74159
^ Lossin, C. (2009). A catalog of SCN1A variants. Brain and Development, 31(2), 114–130. https://doi.org/10.1016/j.braindev.2008.07.011
^ ^a ^b Fujiwara, T., Sugawara, T., Mazaki‐Miyazaki, E., Takahashi, Y., Fukushima, K., Watanabe, M., … Inoue, Y. (2003). Mutations of sodium channel α subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic–clonic seizures. Brain, 126(3), 531–546. https://doi.org/10.1093/brain/awg053
^ Ohmori, I., Kahlig, K. M., Rhodes, T. H., Wang, D. W., & George, A. L. (2006). Nonfunctional SCN1A Is Common in Severe Myoclonic Epilepsy of Infancy. Epilepsia, 47(10), 1636–1642. https://doi.org/10.1111/j.1528-1167.2006.00643.x
^ 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.
^ Bulman, D. E. (1997). Phenotype Variation and Newcomers in Ion Channel Disorders. Human Molecular Genetics, 6(10), 1679–1685. https://doi.org/10.1093/hmg/6.10.1679
^ 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.
^ Yu, F. H., Mantegazza, M., Westenbroek, R. E., Robbins, C. A., Kalume, F., Burton, K. A., … Catterall, W. A. (2006). Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nature Neuroscience, 9(9), 1142–1149. https://doi.org/10.1038/nn1754
^ Escayg A, MacDonald BT, Meisler MH, Baulac S, Huberfeld G, An-Gourfinkel I, et al. (april 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. S2CID 29543172.
^ Spampanato J, Escayg A, Meisler MH, Goldin AL (oktobar 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. doi:10.1523/jneurosci.21-19-07481.2001. PMC 6762922. PMID 11567038.
^ Nabbout R, Gennaro E, Dalla Bernardina B, Dulac O, Madia F, Bertini E, et al. (juni 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. S2CID 604240.
^ Lossin C. "SCN1A infobase". Pristupljeno 30. 10. 2009. compilation of genetic variations in the SCN1A gene that alter the expression or function of Nav1.1
^ Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC (januar 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. doi:10.1523/jneurosci.18-01-00128.1998. PMC 6793384. PMID 9412493.

Dopunska literatura[uredi | uredi izvor]

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 (januar 2002). "The role of sodium channels in cell adhesion". Frontiers in Bioscience. 7 (1–3): 12–23. doi:10.2741/isom. PMID 11779698.
Kanai K, Hirose S, Oguni H, Fukuma G, Shirasaka Y, Miyajima T, et al. (juli 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. 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 (juni 2005). "SCN1A mutations and epilepsy". Human Mutation. 25 (6): 535–42. doi:10.1002/humu.20178. PMID 15880351. S2CID 19148287.
Catterall WA, Goldin AL, Waxman SG (decembar 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. S2CID 7332624.
Lu CM, Han J, Rado TA, Brown GB (maj 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. S2CID 29330026.
Goldin AL, Snutch T, Lübbert H, Dowsett A, Marshall J, Auld V, et al. (oktobar 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. Bibcode:1986PNAS...83.7503G. doi:10.1073/pnas.83.19.7503. PMC 386747. 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. doi:10.1159/000133818. PMID 8062593.
Peiffer A, Thompson J, Charlier C, Otterud B, Varvil T, Pappas C, et al. (oktobar 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. 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. doi:10.1086/319516. PMC 1275639. 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. doi:10.1086/319524. PMC 1275640. PMID 11254445.
Whitaker WR, Faull RL, Waldvogel HJ, Plumpton CJ, Emson PC, Clare JJ (mart 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 (juni 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, et al. (august 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. S2CID 45138036.
Abou-Khalil B, Ge Q, Desai R, Ryther R, Bazyk A, Bailey R, et al. (decembar 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. S2CID 26448714.
Ito M, Nagafuji H, Okazawa H, Yamakawa K, Sugawara T, Mazaki-Miyazaki E, et al. (januar 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. S2CID 25555020.

Vanjski linkovi[uredi | uredi izvor]

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

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000144285 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000064329 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: SCN1A sodium channel, voltage-gated, type I, alpha subunit".

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[pmid1315496-14] George AL, Komisarof J, Kallen RG, Barchi RL (februar 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. S2CID 37892568.

[pmid1309946-15] Gellens ME, George AL, Chen LQ, Chahine M, Horn R, Barchi RL, Kallen RG (januar 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. Bibcode:1992PNAS...89..554G. doi:10.1073/pnas.89.2.554. PMC 48277. PMID 1309946.

[16] Escayg, A., MacDonald, B. T., Meisler, M. H., Baulac, S., Huberfeld, G., An-Gourfinkel, I., … Malafosse, A. (2000). Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2. Nature Genetics, 24(4), 343–345. https://doi.org/10.1038/74159

[17] Lossin, C. (2009). A catalog of SCN1A variants. Brain and Development, 31(2), 114–130. https://doi.org/10.1016/j.braindev.2008.07.011

[:3-18] Fujiwara, T., Sugawara, T., Mazaki‐Miyazaki, E., Takahashi, Y., Fukushima, K., Watanabe, M., … Inoue, Y. (2003). Mutations of sodium channel α subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic–clonic seizures. Brain, 126(3), 531–546. https://doi.org/10.1093/brain/awg053

[19] Ohmori, I., Kahlig, K. M., Rhodes, T. H., Wang, D. W., & George, A. L. (2006). Nonfunctional SCN1A Is Common in Severe Myoclonic Epilepsy of Infancy. Epilepsia, 47(10), 1636–1642. https://doi.org/10.1111/j.1528-1167.2006.00643.x

[20] 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.

[21] Bulman, D. E. (1997). Phenotype Variation and Newcomers in Ion Channel Disorders. Human Molecular Genetics, 6(10), 1679–1685. https://doi.org/10.1093/hmg/6.10.1679

[22] 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.

[23] Yu, F. H., Mantegazza, M., Westenbroek, R. E., Robbins, C. A., Kalume, F., Burton, K. A., … Catterall, W. A. (2006). Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nature Neuroscience, 9(9), 1142–1149. https://doi.org/10.1038/nn1754

[pmid10742094-24] Escayg A, MacDonald BT, Meisler MH, Baulac S, Huberfeld G, An-Gourfinkel I, et al. (april 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. S2CID 29543172.

[pmid11567038-25] Spampanato J, Escayg A, Meisler MH, Goldin AL (oktobar 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. doi:10.1523/jneurosci.21-19-07481.2001. PMC 6762922. PMID 11567038.

[pmid12821740-26] Nabbout R, Gennaro E, Dalla Bernardina B, Dulac O, Madia F, Bertini E, et al. (juni 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. S2CID 604240.

[urlwww.scn1a.info_–_SCN1A_infobase-27] Lossin C. "SCN1A infobase". Pristupljeno 30. 10. 2009. compilation of genetic variations in the SCN1A gene that alter the expression or function of Nav1.1

[pmid9412493-28] Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC (januar 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. doi:10.1523/jneurosci.18-01-00128.1998. PMC 6793384. PMID 9412493.

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