Sodium channel protein type 5 subunit alpha

Details

Name
Sodium channel protein type 5 subunit alpha
Synonyms
  • HH1
  • Sodium channel protein cardiac muscle subunit alpha
  • Sodium channel protein type V subunit alpha
  • Voltage-gated sodium channel subunit alpha Nav1.5
Gene Name
SCN5A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0036969|Sodium channel protein type 5 subunit alpha
MANFLLPRGTSSFRRFTRESLAAIEKRMAEKQARGSTTLQESREGLPEEEAPRPQLDLQA
SKKLPDLYGNPPQELIGEPLEDLDPFYSTQKTFIVLNKGKTIFRFSATNALYVLSPFHPI
RRAAVKILVHSLFNMLIMCTILTNCVFMAQHDPPPWTKYVEYTFTAIYTFESLVKILARG
FCLHAFTFLRDPWNWLDFSVIIMAYTTEFVDLGNVSALRTFRVLRALKTISVISGLKTIV
GALIQSVKKLADVMVLTVFCLSVFALIGLQLFMGNLRHKCVRNFTALNGTNGSVEADGLV
WESLDLYLSDPENYLLKNGTSDVLLCGNSSDAGTCPEGYRCLKAGENPDHGYTSFDSFAW
AFLALFRLMTQDCWERLYQQTLRSAGKIYMIFFMLVIFLGSFYLVNLILAVVAMAYEEQN
QATIAETEEKEKRFQEAMEMLKKEHEALTIRGVDTVSRSSLEMSPLAPVNSHERRSKRRK
RMSSGTEECGEDRLPKSDSEDGPRAMNHLSLTRGLSRTSMKPRSSRGSIFTFRRRDLGSE
ADFADDENSTAGESESHHTSLLVPWPLRRTSAQGQPSPGTSAPGHALHGKKNSTVDCNGV
VSLLGAGDPEATSPGSHLLRPVMLEHPPDTTTPSEEPGGPQMLTSQAPCVDGFEEPGARQ
RALSAVSVLTSALEELEESRHKCPPCWNRLAQRYLIWECCPLWMSIKQGVKLVVMDPFTD
LTITMCIVLNTLFMALEHYNMTSEFEEMLQVGNLVFTGIFTAEMTFKIIALDPYYYFQQG
WNIFDSIIVILSLMELGLSRMSNLSVLRSFRLLRVFKLAKSWPTLNTLIKIIGNSVGALG
NLTLVLAIIVFIFAVVGMQLFGKNYSELRDSDSGLLPRWHMMDFFHAFLIIFRILCGEWI
ETMWDCMEVSGQSLCLLVFLLVMVIGNLVVLNLFLALLLSSFSADNLTAPDEDREMNNLQ
LALARIQRGLRFVKRTTWDFCCGLLRQRPQKPAALAAQGQLPSCIATPYSPPPPETEKVP
PTRKETRFEEGEQPGQGTPGDPEPVCVPIAVAESDTDDQEEDEENSLGTEEESSKQQESQ
PVSGGPEAPPDSRTWSQVSATASSEAEASASQADWRQQWKAEPQAPGCGETPEDSCSEGS
TADMTNTAELLEQIPDLGQDVKDPEDCFTEGCVRRCPCCAVDTTQAPGKVWWRLRKTCYH
IVEHSWFETFIIFMILLSSGALAFEDIYLEERKTIKVLLEYADKMFTYVFVLEMLLKWVA
YGFKKYFTNAWCWLDFLIVDVSLVSLVANTLGFAEMGPIKSLRTLRALRPLRALSRFEGM
RVVVNALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFGRCINQTEGDLPLNYTIVNN
KSQCESLNLTGELYWTKVKVNFDNVGAGYLALLQVATFKGWMDIMYAAVDSRGYEEQPQW
EYNLYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKK
LGSKKPQKPIPRPLNKYQGFIFDIVTKQAFDVTIMFLICLNMVTMMVETDDQSPEKINIL
AKINLLFVAIFTGECIVKLAALRHYYFTNSWNIFDFVVVILSIVGTVLSDIIQKYFFSPT
LFRVIRLARIGRILRLIRGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYSIFGMANFA
YVKWEAGIDDMFNFQTFANSMLCLFQITTSAGWDGLLSPILNTGPPYCDPTLPNSNGSRG
DCGSPAVGILFFTTYIIISFLIVVNMYIAIILENFSVATEESTEPLSEDDFDMFYEIWEK
FDPEATQFIEYSVLSDFADALSEPLRIAKPNQISLINMDLPMVSGDRIHCMDILFAFTKR
VLGESGEMDALKIQMEEKFMAANPSKISYEPITTTLRRKHEEVSAMVIQRAFRRHLLQRS
LKHASFLFRQQAGSGLSEEDAPEREGLIAYVMSENFSRPLGPPSSSSISSTSFPPSYDSV
TRATSDNLQVRGSDYSHSEDLADFPPSPDRDRESIV
Number of residues
2016
Molecular Weight
226937.475
Theoretical pI
5.23
GO Classification
Functions
ankyrin binding / calmodulin binding / enzyme binding / fibroblast growth factor binding / ion channel binding / nitric-oxide synthase binding / protein domain specific binding / protein kinase binding / scaffold protein binding / ubiquitin protein ligase binding / voltage-gated sodium channel activity / voltage-gated sodium channel activity involved in AV node cell action potential / voltage-gated sodium channel activity involved in bundle of His cell action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / voltage-gated sodium channel activity involved in SA node cell action potential
Processes
AV node cell action potential / AV node cell to bundle of His cell communication / axon guidance / brainstem development / bundle of His cell action potential / cardiac muscle cell action potential involved in contraction / cardiac muscle contraction / cardiac ventricle development / cellular response to calcium ion / cerebellum development / membrane depolarization / membrane depolarization during action potential / membrane depolarization during AV node cell action potential / membrane depolarization during bundle of His cell action potential / membrane depolarization during cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / membrane depolarization during SA node cell action potential / neuronal action potential / odontogenesis of dentin-containing tooth / positive regulation of action potential / positive regulation of epithelial cell proliferation / positive regulation of sodium ion transport / regulation of atrial cardiac muscle cell membrane depolarization / regulation of atrial cardiac muscle cell membrane repolarization / regulation of cardiac muscle cell contraction / regulation of heart rate / regulation of heart rate by cardiac conduction / regulation of sodium ion transmembrane transport / regulation of ventricular cardiac muscle cell membrane depolarization / regulation of ventricular cardiac muscle cell membrane repolarization / response to denervation involved in regulation of muscle adaptation / SA node cell action potential / sodium ion transmembrane transport / sodium ion transport / telencephalon development / ventricular cardiac muscle cell action potential
Components
caveola / cell surface / endoplasmic reticulum / integral component of membrane / intercalated disc / intracellular / lateral plasma membrane / plasma membrane / sarcolemma / T-tubule / voltage-gated sodium channel complex / Z disc
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Pfam Domain Function
Transmembrane Regions
127-150 159-178 192-210 217-236 253-276 390-415 712-736 748-771 780-799 806-825 842-862 914-939 1201-1224 1238-1263 1270-1291 1296-1317 1337-1359 1444-1470 1524-1547 1559-1582 1589-1612 1623-1644 1660-1682 1748-1772
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0009999|Sodium channel protein type 5 subunit alpha (SCN5A)
ATGGCAAACTTCCTATTACCTCGGGGCACCAGCAGCTTCCGCAGGTTCACACGGGAGTCC
CTGGCAGCCATCGAGAAGCGCATGGCAGAGAAGCAAGCCCGCGGCTCAACCACCTTGCAG
GAGAGCCGAGAGGGGCTGCCCGAGGAGGAGGCTCCCCGGCCCCAGCTGGACCTGCAGGCC
TCCAAAAAGCTGCCAGATCTCTATGGCAATCCACCCCAAGAGCTCATCGGAGAGCCCCTG
GAGGACCTGGACCCCTTCTATAGCACCCAAAAGACTTTCATCGTACTGAATAAAGGCAAG
ACCATCTTCCGGTTCAGTGCCACCAACGCCTTGTATGTCCTCAGTCCCTTCCACCCCATC
CGGAGAGCGGCTGTGAAGATTCTGGTTCACTCGCTCTTCAACATGCTCATCATGTGCACC
ATCCTCACCAACTGCGTGTTCATGGCCCAGCACGACCCTCCACCCTGGACCAAGTATGTC
GAGTACACCTTCACCGCCATTTACACCTTTGAGTCTCTGGTCAAGATTCTGGCTCGAGGC
TTCTGCCTGCACGCGTTCACTTTCCTTCGGGACCCATGGAACTGGCTGGACTTTAGTGTG
ATTATCATGGCATACACAACTGAATTTGTGGACCTGGGCAATGTCTCAGCCTTACGCACC
TTCCGAGTCCTCCGGGCCCTGAAAACTATATCAGTCATTTCAGGGCTGAAGACCATCGTG
GGGGCCCTGATCCAGTCTGTGAAGAAGCTGGCTGATGTGATGGTCCTCACAGTCTTCTGC
CTCAGCGTCTTTGCCCTCATCGGCCTGCAGCTCTTCATGGGCAACCTAAGGCACAAGTGC
GTGCGCAACTTCACAGCGCTCAACGGCACCAACGGCTCCGTGGAGGCCGACGGCTTGGTC
TGGGAATCCCTGGACCTTTACCTCAGTGATCCAGAAAATTACCTGCTCAAGAACGGCACC
TCTGATGTGTTACTGTGTGGGAACAGCTCTGACGCTGGGACATGTCCGGAGGGCTACCGG
TGCCTAAAGGCAGGCGAGAACCCCGACCACGGCTACACCAGCTTCGATTCCTTTGCCTGG
GCCTTTCTTGCACTCTTCCGCCTGATGACGCAGGACTGCTGGGAGCGCCTCTATCAGCAG
ACCCTCAGGTCCGCAGGGAAGATCTACATGATCTTCTTCATGCTTGTCATCTTCCTGGGG
TCCTTCTACCTGGTGAACCTGATCCTGGCCGTGGTCGCAATGGCCTATGAGGAGCAAAAC
CAAGCCACCATCGCTGAGACCGAGGAGAAGGAAAAGCGCTTCCAGGAGGCCATGGAAATG
CTCAAGAAAGAACACGAGGCCCTCACCATCAGGGGTGTGGATACCGTGTCCCGTAGCTCC
TTGGAGATGTCCCCTTTGGCCCCAGTAAACAGCCATGAGAGAAGAAGCAAGAGGAGAAAA
CGGATGTCTTCAGGAACTGAGGAGTGTGGGGAGGACAGGCTCCCCAAGTCTGACTCAGAA
GATGGTCCCAGAGCAATGAATCATCTCAGCCTCACCCGTGGCCTCAGCAGGACTTCTATG
AAGCCACGTTCCAGCCGCGGGAGCATTTTCACCTTTCGCAGGCGAGACCTGGGTTCTGAA
GCAGATTTTGCAGATGATGAAAACAGCACAGCGGGGGAGAGCGAGAGCCACCACACATCA
CTGCTGGTGCCCTGGCCCCTGCGCCGGACCAGTGCCCAGGGACAGCCCAGTCCCGGAACC
TCGGCTCCTGGCCACGCCCTCCATGGCAAAAAGAACAGCACTGTGGACTGCAATGGGGTG
GTCTCATTACTGGGGGCAGGCGACCCAGAGGCCACATCCCCAGGAAGCCACCTCCTCCGC
CCTGTGATGCTAGAGCACCCGCCAGACACGACCACGCCATCGGAGGAGCCAGGCGGGCCC
CAGATGCTGACCTCCCAGGCTCCGTGTGTAGATGGCTTCGAGGAGCCAGGAGCACGGCAG
CGGGCCCTCAGCGCAGTCAGCGTCCTCACCAGCGCACTGGAAGAGTTAGAGGAGTCTCGC
CACAAGTGTCCACCATGCTGGAACCGTCTCGCCCAGCGCTACCTGATCTGGGAGTGCTGC
CCGCTGTGGATGTCCATCAAGCAGGGAGTGAAGTTGGTGGTCATGGACCCGTTTACTGAC
CTCACCATCACTATGTGCATCGTACTCAACACACTCTTCATGGCGCTGGAGCACTACAAC
ATGACAAGTGAATTCGAGGAGATGCTGCAGGTCGGAAACCTGGTCTTCACAGGGATTTTC
ACAGCAGAGATGACCTTCAAGATCATTGCCCTCGACCCCTACTACTACTTCCAACAGGGC
TGGAACATCTTCGACAGCATCATCGTCATCCTTAGCCTCATGGAGCTGGGCCTGTCCCGC
ATGAGCAACTTGTCGGTGCTGCGCTCCTTCCGCCTGCTGCGGGTCTTCAAGCTGGCCAAA
TCATGGCCCACCCTGAACACACTCATCAAGATCATCGGGAACTCAGTGGGGGCACTGGGG
AACCTGACACTGGTGCTAGCCATCATCGTGTTCATCTTTGCTGTGGTGGGCATGCAGCTC
TTTGGCAAGAACTACTCGGAGCTGAGGGACAGCGACTCAGGCCTGCTGCCTCGCTGGCAC
ATGATGGACTTCTTTCATGCCTTCCTCATCATCTTCCGCATCCTCTGTGGAGAGTGGATC
GAGACCATGTGGGACTGCATGGAGGTGTCGGGGCAGTCATTATGCCTGCTGGTCTTCTTG
CTTGTTATGGTCATTGGCAACCTTGTGGTCCTGAATCTCTTCCTGGCCTTGCTGCTCAGC
TCCTTCAGTGCAGACAACCTCACAGCCCCTGATGAGGACAGAGAGATGAACAACCTCCAG
CTGGCCCTGGCCCGCATCCAGAGGGGCCTGCGCTTTGTCAAGCGGACCACCTGGGATTTC
TGCTGTGGTCTCCTGCGGCAGCGGCCTCAGAAGCCCGCAGCCCTTGCCGCCCAGGGCCAG
CTGCCCAGCTGCATTGCCACCCCCTACTCCCCGCCACCCCCAGAGACGGAGAAGGTGCCT
CCCACCCGCAAGGAAACACGGTTTGAGGAAGGCGAGCAACCAGGCCAGGGCACCCCCGGG
GATCCAGAGCCCGTGTGTGTGCCCATCGCTGTGGCCGAGTCAGACACAGATGACCAAGAA
GAAGATGAGGAGAACAGCCTGGGCACGGAGGAGGAGTCCAGCAAGCAGGAATCCCAGCCT
GTGTCCGGTGGCCCAGAGGCCCCTCCGGATTCCAGGACCTGGAGCCAGGTGTCAGCGACT
GCCTCCTCTGAGGCCGAGGCCAGTGCATCTCAGGCCGACTGGCGGCAGCAGTGGAAAGCG
GAACCCCAGGCCCCAGGGTGCGGTGAGACCCCAGAGGACAGTTGCTCCGAGGGCAGCACA
GCAGACATGACCAACACCGCTGAGCTCCTGGAGCAGATCCCTGACCTCGGCCAGGATGTC
AAGGACCCAGAGGACTGCTTCACTGAAGGCTGTGTCCGGCGCTGTCCCTGCTGTGCGGTG
GACACCACACAGGCCCCAGGGAAGGTCTGGTGGCGGTTGCGCAAGACCTGCTACCACATC
GTGGAGCACAGCTGGTTCGAGACATTCATCATCTTCATGATCCTACTCAGCAGTGGAGCG
CTGGCCTTCGAGGACATCTACCTAGAGGAGCGGAAGACCATCAAGGTTCTGCTTGAGTAT
GCCGACAAGATGTTCACATATGTCTTCGTGCTGGAGATGCTGCTCAAGTGGGTGGCCTAC
GGCTTCAAGAAGTACTTCACCAATGCCTGGTGCTGGCTCGACTTCCTCATCGTAGACGTC
TCTCTGGTCAGCCTGGTGGCCAACACCCTGGGCTTTGCCGAGATGGGCCCCATCAAGTCA
CTGCGGACGCTGCGTGCACTCCGTCCTCTGAGAGCTCTGTCACGATTTGAGGGCATGAGG
GTGGTGGTCAATGCCCTGGTGGGCGCCATCCCGTCCATCATGAACGTCCTCCTCGTCTGC
CTCATCTTCTGGCTCATCTTCAGCATCATGGGCGTGAACCTCTTTGCGGGGAAGTTTGGG
AGGTGCATCAACCAGACAGAGGGAGACTTGCCTTTGAACTACACCATCGTGAACAACAAG
AGCCAGTGTGAGTCCTTGAACTTGACCGGAGAATTGTACTGGACCAAGGTGAAAGTCAAC
TTTGACAACGTGGGGGCCGGGTACCTGGCCCTTCTGCAGGTGGCAACATTTAAAGGCTGG
ATGGACATTATGTATGCAGCTGTGGACTCCAGGGGGTATGAAGAGCAGCCTCAGTGGGAA
TACAACCTCTACATGTACATCTATTTTGTCATTTTCATCATCTTTGGGTCTTTCTTCACC
CTGAACCTCTTTATTGGTGTCATCATTGACAACTTCAACCAACAGAAGAAAAAGTTAGGG
GGCCAGGACATCTTCATGACAGAGGAGCAGAAGAAGTACTACAATGCCATGAAGAAGCTG
GGCTCCAAGAAGCCCCAGAAGCCCATCCCACGGCCCCTGAACAAGTACCAGGGCTTCATA
TTCGACATTGTGACCAAGCAGGCCTTTGACGTCACCATCATGTTTCTGATCTGCTTGAAT
ATGGTGACCATGATGGTGGAGACAGATGACCAAAGTCCTGAGAAAATCAACATCTTGGCC
AAGATCAACCTGCTCTTTGTGGCCATCTTCACAGGCGAGTGTATTGTCAAGCTGGCTGCC
CTGCGCCACTACTACTTCACCAACAGCTGGAATATCTTCGACTTCGTGGTTGTCATCCTC
TCCATCGTGGGCACTGTGCTCTCGGACATCATCCAGAAGTACTTCTTCTCCCCGACGCTC
TTCCGAGTCATCCGCCTGGCCCGAATAGGCCGCATCCTCAGACTGATCCGAGGGGCCAAG
GGGATCCGCACGCTGCTCTTTGCCCTCATGATGTCCCTGCCTGCCCTCTTCAACATCGGG
CTGCTGCTCTTCCTCGTCATGTTCATCTACTCCATCTTTGGCATGGCCAACTTCGCTTAT
GTCAAGTGGGAGGCTGGCATCGACGACATGTTCAACTTCCAGACCTTCGCCAACAGCATG
CTGTGCCTCTTCCAGATCACCACGTCGGCCGGCTGGGATGGCCTCCTCAGCCCCATCCTC
AACACTGGGCCGCCCTACTGCGACCCCACTCTGCCCAACAGCAATGGCTCTCGGGGGGAC
TGCGGGAGCCCAGCCGTGGGCATCCTCTTCTTCACCACCTACATCATCATCTCCTTCCTC
ATCGTGGTCAACATGTACATTGCCATCATCCTGGAGAACTTCAGCGTGGCCACGGAGGAG
AGCACCGAGCCCCTGAGTGAGGACGACTTCGATATGTTCTATGAGATCTGGGAGAAATTT
GACCCAGAGGCCACTCAGTTTATTGAGTATTCGGTCCTGTCTGACTTTGCCGATGCCCTG
TCTGAGCCACTCCGTATCGCCAAGCCCAACCAGATAAGCCTCATCAACATGGACCTGCCC
ATGGTGAGTGGGGACCGCATCCATTGCATGGACATTCTCTTTGCCTTCACCAAAAGGGTC
CTGGGGGAGTCTGGGGAGATGGACGCCCTGAAGATCCAGATGGAGGAGAAGTTCATGGCA
GCCAACCCATCCAAGATCTCCTACGAGCCCATCACCACCACACTCCGGCGCAAGCACGAA
GAGGTGTCGGCCATGGTTATCCAGAGAGCCTTCCGCAGGCACCTGCTGCAACGCTCTTTG
AAGCATGCCTCCTTCCTCTTCCGTCAGCAGGCGGGCAGCGGCCTCTCCGAAGAGGATGCC
CCTGAGCGAGAGGGCCTCATCGCCTACGTGATGAGTGAGAACTTCTCCCGACCCCTTGGC
CCACCCTCCAGCTCCTCCATCTCCTCCACTTCCTTCCCACCCTCCTATGACAGTGTCACT
AGAGCCACCAGCGATAACCTCCAGGTGCGGGGGTCTGACTACAGCCACAGTGAAGATCTC
GCCGACTTCCCCCCTTCTCCGGACAGGGACCGTGAGTCCATCGTGTGA
Chromosome Location
3
Locus
3p21
External Identifiers
ResourceLink
UniProtKB IDQ14524
UniProtKB Entry NameSCN5A_HUMAN
GenBank Protein ID184039
GenBank Gene IDM77235
GenAtlas IDSCN5A
HGNC IDHGNC:10593
General References
  1. Gellens ME, George AL Jr, Chen LQ, Chahine M, Horn R, Barchi RL, Kallen RG: Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):554-8. [PubMed:1309946]
  2. Ou Y, Gibbons SJ, Miller SM, Strege PR, Rich A, Distad MA, Ackerman MJ, Rae JL, Szurszewski JH, Farrugia G: SCN5A is expressed in human jejunal circular smooth muscle cells. Neurogastroenterol Motil. 2002 Oct;14(5):477-86. [PubMed:12358675]
  3. Makielski JC, Ye B, Valdivia CR, Pagel MD, Pu J, Tester DJ, Ackerman MJ: A ubiquitous splice variant and a common polymorphism affect heterologous expression of recombinant human SCN5A heart sodium channels. Circ Res. 2003 Oct 31;93(9):821-8. Epub 2003 Sep 18. [PubMed:14500339]
  4. Ye B, Valdivia CR, Ackerman MJ, Makielski JC: A common human SCN5A polymorphism modifies expression of an arrhythmia causing mutation. Physiol Genomics. 2003 Feb 6;12(3):187-93. [PubMed:12454206]
  5. Ou SW, Kameyama A, Hao LY, Horiuchi M, Minobe E, Wang WY, Makita N, Kameyama M: Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCN5A. Eur J Neurosci. 2005 Aug;22(4):793-801. [PubMed:16115203]
  6. Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Chen R, Chen Z, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang J, Wang J, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA: The DNA sequence, annotation and analysis of human chromosome 3. Nature. 2006 Apr 27;440(7088):1194-8. [PubMed:16641997]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  8. van Bemmelen MX, Rougier JS, Gavillet B, Apotheloz F, Daidie D, Tateyama M, Rivolta I, Thomas MA, Kass RS, Staub O, Abriel H: Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2 mediated ubiquitination. Circ Res. 2004 Aug 6;95(3):284-91. Epub 2004 Jun 24. [PubMed:15217910]
  9. Rougier JS, van Bemmelen MX, Bruce MC, Jespersen T, Gavillet B, Apotheloz F, Cordonier S, Staub O, Rotin D, Abriel H: Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins. Am J Physiol Cell Physiol. 2005 Mar;288(3):C692-701. Epub 2004 Nov 17. [PubMed:15548568]
  10. Dichgans M, Freilinger T, Eckstein G, Babini E, Lorenz-Depiereux B, Biskup S, Ferrari MD, Herzog J, van den Maagdenberg AM, Pusch M, Strom TM: Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet. 2005 Jul 30-Aug 5;366(9483):371-7. [PubMed:16054936]
  11. Valdivia CR, Ueda K, Ackerman MJ, Makielski JC: GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5A. Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1446-52. doi: 10.1152/ajpheart.00513.2009. Epub 2009 Aug 7. [PubMed:19666841]
  12. Wang J, Ou SW, Wang YJ, Kameyama M, Kameyama A, Zong ZH: Analysis of four novel variants of Nav1.5/SCN5A cloned from the brain. Neurosci Res. 2009 Aug;64(4):339-47. doi: 10.1016/j.neures.2009.04.003. Epub 2009 Apr 17. [PubMed:19376164]
  13. Zimmer T, Surber R: SCN5A channelopathies--an update on mutations and mechanisms. Prog Biophys Mol Biol. 2008 Oct-Nov;98(2-3):120-36. doi: 10.1016/j.pbiomolbio.2008.10.005. Epub 2008 Nov 5. [PubMed:19027780]
  14. Schroeter A, Walzik S, Blechschmidt S, Haufe V, Benndorf K, Zimmer T: Structure and function of splice variants of the cardiac voltage-gated sodium channel Na(v)1.5. J Mol Cell Cardiol. 2010 Jul;49(1):16-24. doi: 10.1016/j.yjmcc.2010.04.004. Epub 2010 Apr 14. [PubMed:20398673]
  15. Wang C, Hennessey JA, Kirkton RD, Wang C, Graham V, Puranam RS, Rosenberg PB, Bursac N, Pitt GS: Fibroblast growth factor homologous factor 13 regulates Na+ channels and conduction velocity in murine hearts. Circ Res. 2011 Sep 16;109(7):775-82. doi: 10.1161/CIRCRESAHA.111.247957. Epub 2011 Aug 4. [PubMed:21817159]
  16. Beltran-Alvarez P, Pagans S, Brugada R: The cardiac sodium channel is post-translationally modified by arginine methylation. J Proteome Res. 2011 Aug 5;10(8):3712-9. doi: 10.1021/pr200339n. Epub 2011 Jul 18. [PubMed:21726068]
  17. Marionneau C, Lichti CF, Lindenbaum P, Charpentier F, Nerbonne JM, Townsend RR, Merot J: Mass spectrometry-based identification of native cardiac Nav1.5 channel alpha subunit phosphorylation sites. J Proteome Res. 2012 Dec 7;11(12):5994-6007. doi: 10.1021/pr300702c. Epub 2012 Nov 9. [PubMed:23092124]
  18. Xiao Y, Blumenthal K, Cummins TR: Gating-pore currents demonstrate selective and specific modulation of individual sodium channel voltage-sensors by biological toxins. Mol Pharmacol. 2014 Aug;86(2):159-67. doi: 10.1124/mol.114.092338. Epub 2014 Jun 4. [PubMed:24898004]
  19. Chagot B, Potet F, Balser JR, Chazin WJ: Solution NMR structure of the C-terminal EF-hand domain of human cardiac sodium channel NaV1.5. J Biol Chem. 2009 Mar 6;284(10):6436-45. doi: 10.1074/jbc.M807747200. Epub 2008 Dec 11. [PubMed:19074138]
  20. Chagot B, Chazin WJ: Solution NMR structure of Apo-calmodulin in complex with the IQ motif of human cardiac sodium channel NaV1.5. J Mol Biol. 2011 Feb 11;406(1):106-19. doi: 10.1016/j.jmb.2010.11.046. Epub 2010 Dec 15. [PubMed:21167176]
  21. Wang C, Chung BC, Yan H, Lee SY, Pitt GS: Crystal structure of the ternary complex of a NaV C-terminal domain, a fibroblast growth factor homologous factor, and calmodulin. Structure. 2012 Jul 3;20(7):1167-76. doi: 10.1016/j.str.2012.05.001. Epub 2012 Jun 14. [PubMed:22705208]
  22. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT: SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995 Mar 10;80(5):805-11. [PubMed:7889574]
  23. Wang Q, Shen J, Li Z, Timothy K, Vincent GM, Priori SG, Schwartz PJ, Keating MT: Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia. Hum Mol Genet. 1995 Sep;4(9):1603-7. [PubMed:8541846]
  24. Bennett PB, Yazawa K, Makita N, George AL Jr: Molecular mechanism for an inherited cardiac arrhythmia. Nature. 1995 Aug 24;376(6542):683-5. [PubMed:7651517]
  25. An RH, Wang XL, Kerem B, Benhorin J, Medina A, Goldmit M, Kass RS: Novel LQT-3 mutation affects Na+ channel activity through interactions between alpha- and beta1-subunits. Circ Res. 1998 Jul 27;83(2):141-6. [PubMed:9686753]
  26. Makita N, Shirai N, Nagashima M, Matsuoka R, Yamada Y, Tohse N, Kitabatake A: A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome. FEBS Lett. 1998 Feb 13;423(1):5-9. [PubMed:9506831]
  27. Benhorin J, Goldmit M, MacCluer JW, Blangero J, Goffen R, Leibovitch A, Rahat A, Wang Q, Medina A, Towbin J, Kerem B: Identification of a new SCN5A mutation, D1840G, associated with the long QT syndrome. Mutations in brief no. 153. Online. Hum Mutat. 1998;12(1):72. [PubMed:10627139]
  28. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, Moya A, Borggrefe M, Breithardt G, Ortiz-Lopez R, Wang Z, Antzelevitch C, O'Brien RE, Schulze-Bahr E, Keating MT, Towbin JA, Wang Q: Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature. 1998 Mar 19;392(6673):293-6. [PubMed:9521325]
  29. Wattanasirichaigoon D, Vesely MR, Duggal P, Levine JC, Blume ED, Wolff GS, Edwards SB, Beggs AH: Sodium channel abnormalities are infrequent in patients with long QT syndrome: identification of two novel SCN5A mutations. Am J Med Genet. 1999 Oct 29;86(5):470-6. [PubMed:10508990]
  30. Rook MB, Bezzina Alshinawi C, Groenewegen WA, van Gelder IC, van Ginneken AC, Jongsma HJ, Mannens MM, Wilde AA: Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome. Cardiovasc Res. 1999 Dec;44(3):507-17. [PubMed:10690282]
  31. Wei J, Wang DW, Alings M, Fish F, Wathen M, Roden DM, George AL Jr: Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel. Circulation. 1999 Jun 22;99(24):3165-71. [PubMed:10377081]
  32. Dumaine R, Towbin JA, Brugada P, Vatta M, Nesterenko DV, Nesterenko VV, Brugada J, Brugada R, Antzelevitch C: Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. Circ Res. 1999 Oct 29;85(9):803-9. [PubMed:10532948]
  33. Bezzina C, Veldkamp MW, van Den Berg MP, Postma AV, Rook MB, Viersma JW, van Langen IM, Tan-Sindhunata G, Bink-Boelkens MT, van Der Hout AH, Mannens MM, Wilde AA: A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res. 1999 Dec 3-17;85(12):1206-13. [PubMed:10590249]
  34. Schott JJ, Alshinawi C, Kyndt F, Probst V, Hoorntje TM, Hulsbeek M, Wilde AA, Escande D, Mannens MM, Le Marec H: Cardiac conduction defects associate with mutations in SCN5A. Nat Genet. 1999 Sep;23(1):20-1. [PubMed:10471492]
  35. Makita N, Shirai N, Wang DW, Sasaki K, George AL Jr, Kanno M, Kitabatake A: Cardiac Na(+) channel dysfunction in Brugada syndrome is aggravated by beta(1)-subunit. Circulation. 2000 Jan 4-11;101(1):54-60. [PubMed:10618304]
  36. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT: Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 Sep 5;102(10):1178-85. [PubMed:10973849]
  37. Akai J, Makita N, Sakurada H, Shirai N, Ueda K, Kitabatake A, Nakazawa K, Kimura A, Hiraoka M: A novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome. FEBS Lett. 2000 Aug 11;479(1-2):29-34. [PubMed:10940383]
  38. Schwartz PJ, Priori SG, Dumaine R, Napolitano C, Antzelevitch C, Stramba-Badiale M, Richard TA, Berti MR, Bloise R: A molecular link between the sudden infant death syndrome and the long-QT syndrome. N Engl J Med. 2000 Jul 27;343(4):262-7. [PubMed:10911008]
  39. Abriel H, Cabo C, Wehrens XH, Rivolta I, Motoike HK, Memmi M, Napolitano C, Priori SG, Kass RS: Novel arrhythmogenic mechanism revealed by a long-QT syndrome mutation in the cardiac Na(+) channel. Circ Res. 2001 Apr 13;88(7):740-5. [PubMed:11304498]
  40. Rivolta I, Abriel H, Tateyama M, Liu H, Memmi M, Vardas P, Napolitano C, Priori SG, Kass RS: Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes. J Biol Chem. 2001 Aug 17;276(33):30623-30. Epub 2001 Jun 15. [PubMed:11410597]
  41. Kyndt F, Probst V, Potet F, Demolombe S, Chevallier JC, Baro I, Moisan JP, Boisseau P, Schott JJ, Escande D, Le Marec H: Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family. Circulation. 2001 Dec 18;104(25):3081-6. [PubMed:11748104]
  42. Ackerman MJ, Siu BL, Sturner WQ, Tester DJ, Valdivia CR, Makielski JC, Towbin JA: Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA. 2001 Nov 14;286(18):2264-9. [PubMed:11710892]
  43. Tan HL, Bink-Boelkens MT, Bezzina CR, Viswanathan PC, Beaufort-Krol GC, van Tintelen PJ, van den Berg MP, Wilde AA, Balser JR: A sodium-channel mutation causes isolated cardiac conduction disease. Nature. 2001 Feb 22;409(6823):1043-7. [PubMed:11234013]
  44. Smits JP, Eckardt L, Probst V, Bezzina CR, Schott JJ, Remme CA, Haverkamp W, Breithardt G, Escande D, Schulze-Bahr E, LeMarec H, Wilde AA: Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. J Am Coll Cardiol. 2002 Jul 17;40(2):350-6. [PubMed:12106943]
  45. Wang DW, Viswanathan PC, Balser JR, George AL Jr, Benson DW: Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. Circulation. 2002 Jan 22;105(3):341-6. [PubMed:11804990]
  46. Clancy CE, Rudy Y: Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism. Circulation. 2002 Mar 12;105(10):1208-13. [PubMed:11889015]
  47. Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, Bloise R, Giustetto C, De Nardis R, Grillo M, Ronchetti E, Faggiano G, Nastoli J: Natural history of Brugada syndrome: insights for risk stratification and management. Circulation. 2002 Mar 19;105(11):1342-7. [PubMed:11901046]
  48. Yang P, Kanki H, Drolet B, Yang T, Wei J, Viswanathan PC, Hohnloser SH, Shimizu W, Schwartz PJ, Stanton M, Murray KT, Norris K, George AL Jr, Roden DM: Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation. 2002 Apr 23;105(16):1943-8. [PubMed:11997281]
  49. Vatta M, Dumaine R, Varghese G, Richard TA, Shimizu W, Aihara N, Nademanee K, Brugada R, Brugada J, Veerakul G, Li H, Bowles NE, Brugada P, Antzelevitch C, Towbin JA: Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. Hum Mol Genet. 2002 Feb 1;11(3):337-45. [PubMed:11823453]
  50. Chen S, Chung MK, Martin D, Rozich R, Tchou PJ, Wang Q: SNP S1103Y in the cardiac sodium channel gene SCN5A is associated with cardiac arrhythmias and sudden death in a white family. J Med Genet. 2002 Dec;39(12):913-5. [PubMed:12471205]
  51. Vatta M, Dumaine R, Antzelevitch C, Brugada R, Li H, Bowles NE, Nademanee K, Brugada J, Brugada P, Towbin JA: Novel mutations in domain I of SCN5A cause Brugada syndrome. Mol Genet Metab. 2002 Apr;75(4):317-24. [PubMed:12051963]
  52. Rivolta I, Clancy CE, Tateyama M, Liu H, Priori SG, Kass RS: A novel SCN5A mutation associated with long QT-3: altered inactivation kinetics and channel dysfunction. Physiol Genomics. 2002 Sep 3;10(3):191-7. [PubMed:12209021]
  53. Splawski I, Timothy KW, Tateyama M, Clancy CE, Malhotra A, Beggs AH, Cappuccio FP, Sagnella GA, Kass RS, Keating MT: Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. Science. 2002 Aug 23;297(5585):1333-6. [PubMed:12193783]
  54. Groenewegen WA, Firouzi M, Bezzina CR, Vliex S, van Langen IM, Sandkuijl L, Smits JP, Hulsbeek M, Rook MB, Jongsma HJ, Wilde AA: A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill. Circ Res. 2003 Jan 10;92(1):14-22. [PubMed:12522116]
  55. Bezzina CR, Rook MB, Groenewegen WA, Herfst LJ, van der Wal AC, Lam J, Jongsma HJ, Wilde AA, Mannens MM: Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system. Circ Res. 2003 Feb 7;92(2):159-68. [PubMed:12574143]
  56. Wehrens XH, Rossenbacker T, Jongbloed RJ, Gewillig M, Heidbuchel H, Doevendans PA, Vos MA, Wellens HJ, Kass RS: A novel mutation L619F in the cardiac Na+ channel SCN5A associated with long-QT syndrome (LQT3): a role for the I-II linker in inactivation gating. Hum Mutat. 2003 May;21(5):552. [PubMed:12673799]
  57. Viswanathan PC, Benson DW, Balser JR: A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation. J Clin Invest. 2003 Feb;111(3):341-6. [PubMed:12569159]
  58. Benson DW, Wang DW, Dyment M, Knilans TK, Fish FA, Strieper MJ, Rhodes TH, George AL Jr: Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest. 2003 Oct;112(7):1019-28. [PubMed:14523039]
  59. Valdivia CR, Tester DJ, Rok BA, Porter CB, Munger TM, Jahangir A, Makielski JC, Ackerman MJ: A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs. Cardiovasc Res. 2004 Apr 1;62(1):53-62. [PubMed:15023552]
  60. McNair WP, Ku L, Taylor MR, Fain PR, Dao D, Wolfel E, Mestroni L: SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation. 2004 Oct 12;110(15):2163-7. Epub 2004 Oct 4. [PubMed:15466643]
  61. Shin DJ, Jang Y, Park HY, Lee JE, Yang K, Kim E, Bae Y, Kim J, Kim J, Kim SS, Lee MH, Chahine M, Yoon SK: Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with Brugada syndrome. J Hum Genet. 2004;49(10):573-8. Epub 2004 Aug 26. [PubMed:15338453]
  62. Mohler PJ, Rivolta I, Napolitano C, LeMaillet G, Lambert S, Priori SG, Bennett V: Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17533-8. Epub 2004 Dec 3. [PubMed:15579534]
  63. Amin AS, Verkerk AO, Bhuiyan ZA, Wilde AA, Tan HL: Novel Brugada syndrome-causing mutation in ion-conducting pore of cardiac Na+ channel does not affect ion selectivity properties. Acta Physiol Scand. 2005 Dec;185(4):291-301. [PubMed:16266370]
  64. Yokoi H, Makita N, Sasaki K, Takagi Y, Okumura Y, Nishino T, Makiyama T, Kitabatake A, Horie M, Watanabe I, Tsutsui H: Double SCN5A mutation underlying asymptomatic Brugada syndrome. Heart Rhythm. 2005 Mar;2(3):285-92. [PubMed:15851320]
  65. Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S: Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005 Dec 21;294(23):2975-80. [PubMed:16414944]
  66. Tester DJ, Will ML, Haglund CM, Ackerman MJ: Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005 May;2(5):507-17. [PubMed:15840476]
  67. Makiyama T, Akao M, Tsuji K, Doi T, Ohno S, Takenaka K, Kobori A, Ninomiya T, Yoshida H, Takano M, Makita N, Yanagisawa F, Higashi Y, Takeyama Y, Kita T, Horie M: High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations. J Am Coll Cardiol. 2005 Dec 6;46(11):2100-6. Epub 2005 Nov 4. [PubMed:16325048]
  68. Keller DI, Huang H, Zhao J, Frank R, Suarez V, Delacretaz E, Brink M, Osswald S, Schwick N, Chahine M: A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation. Cardiovasc Res. 2006 Jun 1;70(3):521-9. Epub 2006 Mar 3. [PubMed:16616735]
  69. Cordeiro JM, Barajas-Martinez H, Hong K, Burashnikov E, Pfeiffer R, Orsino AM, Wu YS, Hu D, Brugada J, Brugada P, Antzelevitch C, Dumaine R, Brugada R: Compound heterozygous mutations P336L and I1660V in the human cardiac sodium channel associated with the Brugada syndrome. Circulation. 2006 Nov 7;114(19):2026-33. Epub 2006 Oct 30. [PubMed:17075016]
  70. Millat G, Chevalier P, Restier-Miron L, Da Costa A, Bouvagnet P, Kugener B, Fayol L, Gonzalez Armengod C, Oddou B, Chanavat V, Froidefond E, Perraudin R, Rousson R, Rodriguez-Lafrasse C: Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome. Clin Genet. 2006 Sep;70(3):214-27. [PubMed:16922724]
  71. Liang P, Liu WL, Hu DY, Li CL, Tao WH, Li L: [Novel SCN5A gene mutations associated with Brugada syndrome: V95I, A1649V and delF1617]. Zhonghua Xin Xue Guan Bing Za Zhi. 2006 Jul;34(7):616-9. [PubMed:17081365]
  72. Bankston JR, Sampson KJ, Kateriya S, Glaaser IW, Malito DL, Chung WK, Kass RS: A novel LQT-3 mutation disrupts an inactivation gate complex with distinct rate-dependent phenotypic consequences. Channels (Austin). 2007 Jul-Aug;1(4):273-80. Epub 2007 Aug 31. [PubMed:18708744]
  73. Pfahnl AE, Viswanathan PC, Weiss R, Shang LL, Sanyal S, Shusterman V, Kornblit C, London B, Dudley SC Jr: A sodium channel pore mutation causing Brugada syndrome. Heart Rhythm. 2007 Jan;4(1):46-53. Epub 2006 Sep 28. [PubMed:17198989]
  74. Bankston JR, Yue M, Chung W, Spyres M, Pass RH, Silver E, Sampson KJ, Kass RS: A novel and lethal de novo LQT-3 mutation in a newborn with distinct molecular pharmacology and therapeutic response. PLoS One. 2007 Dec 5;2(12):e1258. [PubMed:18060054]
  75. Tian L, Zhu JF, Yang JG: [Gene (SCN5A) mutation analysis of a Chinese family with Brugada syndrome]. Zhonghua Xin Xue Guan Bing Za Zhi. 2007 Dec;35(12):1122-5. [PubMed:18341814]
  76. Zhang Y, Wang T, Ma A, Zhou X, Gui J, Wan H, Shi R, Huang C, Grace AA, Huang CL, Trump D, Zhang H, Zimmer T, Lei M: Correlations between clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in the cardiac Na+ channel. Acta Physiol (Oxf). 2008 Dec;194(4):311-23. doi: 10.1111/j.1748-1716.2008.01883.x. Epub 2008 Jul 24. [PubMed:18616619]
  77. Bebarova M, O'Hara T, Geelen JL, Jongbloed RJ, Timmermans C, Arens YH, Rodriguez LM, Rudy Y, Volders PG: Subepicardial phase 0 block and discontinuous transmural conduction underlie right precordial ST-segment elevation by a SCN5A loss-of-function mutation. Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H48-58. doi: 10.1152/ajpheart.91495.2007. Epub 2008 May 2. [PubMed:18456723]
  78. Petitprez S, Jespersen T, Pruvot E, Keller DI, Corbaz C, Schlapfer J, Abriel H, Kucera JP: Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome. Cardiovasc Res. 2008 Jun 1;78(3):494-504. doi: 10.1093/cvr/cvn023. Epub 2008 Feb 5. [PubMed:18252757]
  79. Barajas-Martinez HM, Hu D, Cordeiro JM, Wu Y, Kovacs RJ, Meltser H, Kui H, Elena B, Brugada R, Antzelevitch C, Dumaine R: Lidocaine-induced Brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel. Circ Res. 2008 Aug 15;103(4):396-404. doi: 10.1161/CIRCRESAHA.108.172619. Epub 2008 Jul 3. [PubMed:18599870]
  80. Darbar D, Kannankeril PJ, Donahue BS, Kucera G, Stubblefield T, Haines JL, George AL Jr, Roden DM: Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. Circulation. 2008 Apr 15;117(15):1927-35. doi: 10.1161/CIRCULATIONAHA.107.757955. Epub 2008 Mar 31. [PubMed:18378609]
  81. Ellinor PT, Nam EG, Shea MA, Milan DJ, Ruskin JN, MacRae CA: Cardiac sodium channel mutation in atrial fibrillation. Heart Rhythm. 2008 Jan;5(1):99-105. Epub 2007 Sep 19. [PubMed:18088563]
  82. Benito B, Brugada R, Perich RM, Lizotte E, Cinca J, Mont L, Berruezo A, Tolosana JM, Freixa X, Brugada P, Brugada J: A mutation in the sodium channel is responsible for the association of long QT syndrome and familial atrial fibrillation. Heart Rhythm. 2008 Oct;5(10):1434-40. doi: 10.1016/j.hrthm.2008.07.013. Epub 2008 Jul 19. [PubMed:18929331]
  83. Lin MT, Wu MH, Chang CC, Chiu SN, Theriault O, Huang H, Christe G, Ficker E, Chahine M: In utero onset of long QT syndrome with atrioventricular block and spontaneous or lidocaine-induced ventricular tachycardia: compound effects of hERG pore region mutation and SCN5A N-terminus variant. Heart Rhythm. 2008 Nov;5(11):1567-74. doi: 10.1016/j.hrthm.2008.08.010. Epub 2008 Aug 17. [PubMed:18848812]
  84. Makiyama T, Akao M, Shizuta S, Doi T, Nishiyama K, Oka Y, Ohno S, Nishio Y, Tsuji K, Itoh H, Kimura T, Kita T, Horie M: A novel SCN5A gain-of-function mutation M1875T associated with familial atrial fibrillation. J Am Coll Cardiol. 2008 Oct 14;52(16):1326-34. doi: 10.1016/j.jacc.2008.07.013. [PubMed:18929244]
  85. Makita N, Behr E, Shimizu W, Horie M, Sunami A, Crotti L, Schulze-Bahr E, Fukuhara S, Mochizuki N, Makiyama T, Itoh H, Christiansen M, McKeown P, Miyamoto K, Kamakura S, Tsutsui H, Schwartz PJ, George AL Jr, Roden DM: The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome. J Clin Invest. 2008 Jun;118(6):2219-29. doi: 10.1172/JCI34057. [PubMed:18451998]
  86. Shan L, Makita N, Xing Y, Watanabe S, Futatani T, Ye F, Saito K, Ibuki K, Watanabe K, Hirono K, Uese K, Ichida F, Miyawaki T, Origasa H, Bowles NE, Towbin JA: SCN5A variants in Japanese patients with left ventricular noncompaction and arrhythmia. Mol Genet Metab. 2008 Apr;93(4):468-74. [PubMed:18368697]
  87. Otagiri T, Kijima K, Osawa M, Ishii K, Makita N, Matoba R, Umetsu K, Hayasaka K: Cardiac ion channel gene mutations in sudden infant death syndrome. Pediatr Res. 2008 Nov;64(5):482-7. doi: 10.1203/PDR.0b013e3181841eca. [PubMed:18596570]
  88. Saito YA, Strege PR, Tester DJ, Locke GR 3rd, Talley NJ, Bernard CE, Rae JL, Makielski JC, Ackerman MJ, Farrugia G: Sodium channel mutation in irritable bowel syndrome: evidence for an ion channelopathy. Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G211-8. doi: 10.1152/ajpgi.90571.2008. Epub 2008 Dec 4. [PubMed:19056759]
  89. Huang H, Millat G, Rodriguez-Lafrasse C, Rousson R, Kugener B, Chevalier P, Chahine M: Biophysical characterization of a new SCN5A mutation S1333Y in a SIDS infant linked to long QT syndrome. FEBS Lett. 2009 Mar 4;583(5):890-6. doi: 10.1016/j.febslet.2009.02.007. Epub 2009 Feb 10. [PubMed:19302788]
  90. Meregalli PG, Tan HL, Probst V, Koopmann TT, Tanck MW, Bhuiyan ZA, Sacher F, Kyndt F, Schott JJ, Albuisson J, Mabo P, Bezzina CR, Le Marec H, Wilde AA: Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. Heart Rhythm. 2009 Mar;6(3):341-8. doi: 10.1016/j.hrthm.2008.11.009. Epub 2008 Nov 11. [PubMed:19251209]
  91. Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ: Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23. [PubMed:19716085]
  92. Hsueh CH, Chen WP, Lin JL, Tsai CT, Liu YB, Juang JM, Tsao HM, Su MJ, Lai LP: Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations. J Biomed Sci. 2009 Feb 20;16:23. doi: 10.1186/1423-0127-16-23. [PubMed:19272188]
  93. Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, Kamakura S, Kyndt F, Koopmann TT, Miyamoto Y, Pfeiffer R, Pollevick GD, Probst V, Zumhagen S, Vatta M, Towbin JA, Shimizu W, Schulze-Bahr E, Antzelevitch C, Salisbury BA, Guicheney P, Wilde AA, Brugada R, Schott JJ, Ackerman MJ: An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2010 Jan;7(1):33-46. doi: 10.1016/j.hrthm.2009.09.069. Epub 2009 Oct 8. [PubMed:20129283]
  94. Shinlapawittayatorn K, Du XX, Liu H, Ficker E, Kaufman ES, Deschenes I: A common SCN5A polymorphism modulates the biophysical defects of SCN5A mutations. Heart Rhythm. 2011 Mar;8(3):455-62. doi: 10.1016/j.hrthm.2010.11.034. Epub 2010 Nov 23. [PubMed:21109022]
  95. Selly JB, Boumahni B, Edmar A, Jamal Bey K, Randrianaivo H, Clerici G, Millat G, Caillet D: [Cardiac sinus node dysfunction due to a new mutation of the SCN5A gene]. Arch Pediatr. 2012 Aug;19(8):837-41. doi: 10.1016/j.arcped.2012.04.017. Epub 2012 Jul 12. [PubMed:22795782]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00192IndecainideapprovedyesinhibitorDetails
DB00252Phenytoinapproved, vet_approvedyesinhibitorDetails
DB00280DisopyramideapprovedyesinhibitorDetails
DB00281Lidocaineapproved, vet_approvedyesinhibitorDetails
DB00379Mexiletineapproved, investigationalyesinhibitorDetails
DB00473Hexylcaineapproved, withdrawnyesinhibitorDetails
DB00527Cinchocaineapproved, vet_approvedyesinhibitorDetails
DB00532Mephenytoinapproved, investigational, withdrawnyesinhibitorDetails
DB00564Carbamazepineapproved, investigationalyesinhibitorDetails
DB00661VerapamilapprovedunknownotherDetails
DB00680Moricizineapproved, investigational, withdrawnyesinhibitorDetails
DB00740Riluzoleapproved, investigationalyesinhibitorDetails
DB00750PrilocaineapprovedyesinhibitorDetails
DB00754EthotoinapprovedyesinhibitorDetails
DB00776OxcarbazepineapprovedyesinhibitorDetails
DB00868BenzonatateapprovedunknownantagonistDetails
DB00908Quinidineapproved, investigationalyesinhibitorDetails
DB01035ProcainamideapprovedunknowninhibitorDetails
DB01056TocainideapprovedyesinhibitorDetails
DB01182PropafenoneapprovedyesinhibitorDetails
DB01195Flecainideapproved, withdrawnyesinhibitorDetails
DB01228Encainideapproved, investigational, withdrawnyesinhibitorDetails
DB00907Cocaineapproved, illicityesinhibitorDetails
DB01320Fosphenytoinapproved, investigationalyesinhibitorDetails
DB01429AprindineexperimentalyesinhibitorDetails
DB00909Zonisamideapproved, investigationalyesinhibitorDetails
DB00243Ranolazineapproved, investigationalyesinhibitorDetails
DB01426Ajmalineapproved, experimentalyesinhibitorDetails
DB01346Quinidine barbiturateapprovedyesinhibitorDetails
DB06217Vernakalantapproved, investigationalyesblockerDetails
DB11633Isavuconazoleapproved, investigationalnoinhibitorDetails