Gene Symbol: SCN5A
Description: sodium voltage-gated channel alpha subunit 5
Alias: CDCD2, CMD1E, CMPD2, HB1, HB2, HBBD, HH1, ICCD, IVF, LQT3, Nav1.5, PFHB1, SSS1, VF1, sodium channel protein type 5 subunit alpha, cardiac tetrodotoxin-insensitive voltage-dependent sodium channel alpha subunit, sodium channel protein cardiac muscle subunit alpha, sodium channel, voltage-gated, type V, alpha subunit, voltage-gated sodium channel subunit alpha Nav1.5
Species: human
Products:     SCN5A

Top Publications

  1. Brisson L, Gillet L, Calaghan S, Besson P, Le Guennec J, Roger S, et al. Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H(+) efflux in caveolae. Oncogene. 2011;30:2070-6 pubmed publisher
    ..Our study suggests that Na(V)1.5 and NHE1 are functionally coupled and enhance the invasiveness of cancer cells by increasing H(+) efflux. ..
  2. Johannessen M, Ramachandran S, Riemer L, Ramos Serrano A, Ruoho A, Jackson M. Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems. Am J Physiol Cell Physiol. 2009;296:C1049-57 pubmed publisher
    ..The modulation of Na(v)1.5 channels by sigma-receptors in the heart suggests an important pathway by which drugs can alter cardiac excitability and rhythmicity. ..
  3. Chagot B, Potet F, Balser J, Chazin W. Solution NMR structure of the C-terminal EF-hand domain of human cardiac sodium channel NaV1.5. J Biol Chem. 2009;284:6436-45 pubmed publisher
    ..These results suggest a molecular basis for the coupling of the intrinsic (EF-hand domain) and extrinsic (calmodulin) components of the calcium-sensing apparatus of NaV1.5. ..
  4. Westenskow P, Splawski I, Timothy K, Keating M, Sanguinetti M. Compound mutations: a common cause of severe long-QT syndrome. Circulation. 2004;109:1834-41 pubmed
    ..Genetic analyses of KVLQT1, HERG, KCNE1, KCNE2, and SCN5A detected compound mutations in 20 of 252 LQTS probands (7.9%)...
  5. Baroudi G, Napolitano C, Priori S, Del Bufalo A, Chahine M. Loss of function associated with novel mutations of the SCN5A gene in patients with Brugada syndrome. Can J Cardiol. 2004;20:425-30 pubmed
    ..Mutations in the SCN5A gene encoding the cardiac voltage-gated Na+ channel (hNav1.5) are associated with Brugada syndrome...
  6. Ueda K, Valdivia C, Medeiros Domingo A, Tester D, Vatta M, Farrugia G, et al. Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proc Natl Acad Sci U S A. 2008;105:9355-60 pubmed publisher
    ..plasma membrane Ca-ATPase subtype 4b (PMCA4b); SNTA1 also is known to associate with the cardiac sodium channel SCN5A. By using a GST-fusion protein of the C terminus of SCN5A, we showed that WT-SNTA1 interacted with SCN5A, nNOS, ..
  7. Yang P, Kanki H, Drolet B, Yang T, Wei J, Viswanathan P, et al. Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation. 2002;105:1943-8 pubmed
    ..The coding regions of the genes encoding the pore-forming channel proteins KvLQT1, HERG, and SCN5A were screened in (1) the same aLQTS cohort (n=92) and (2) controls, drawn from patients tolerating QT-prolonging ..
  8. Kapa S, Tester D, Salisbury B, Harris Kerr C, Pungliya M, Alders M, et al. Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009;120:1752-60 pubmed publisher
    ..Type, frequency, and location of mutations across KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3) were compared between 388 unrelated "definite" (clinical diagnostic score >or=4 and/or QTc >..
  9. Smith J, Lowe J, Kovvali S, Maller J, Salit J, Daly M, et al. Genome-wide association study of electrocardiographic conduction measures in an isolated founder population: Kosrae. Heart Rhythm. 2009;6:634-41 pubmed publisher
    ..SNPs were located in and downstream of the alpha-subunit of the cardiac voltage-gated sodium channel gene SCN5A, with a 4.8 ms (SE 1.0) or 0...

More Information

Publications108 found, 100 shown here

  1. Catterall W, Goldin A, Waxman S. International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev. 2005;57:397-409 pubmed
    ..This article presents the molecular relationships and physiological roles of these sodium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties. ..
  2. Ge J, Sun A, Paajanen V, Wang S, Su C, Yang Z, et al. Molecular and clinical characterization of a novel SCN5A mutation associated with atrioventricular block and dilated cardiomyopathy. Circ Arrhythm Electrophysiol. 2008;1:83-92 pubmed publisher
    Increased susceptibility to dilated cardiomyopathy has been observed in patients carrying mutations in the SCN5A gene, but the underlying mechanism remains unclear...
  3. Holm H, Gudbjartsson D, Arnar D, Thorleifsson G, Thorgeirsson G, Stefansdottir H, et al. Several common variants modulate heart rate, PR interval and QRS duration. Nat Genet. 2010;42:117-22 pubmed publisher
    ..00032, respectively), between TBX5 and advanced atrioventricular block (P = 0.0067), and between SCN10A and pacemaker implantation (P = 0.0029). We also replicated previously described associations with the QT interval. ..
  4. House C, Vaske C, Schwartz A, Obias V, Frank B, Luu T, et al. Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion. Cancer Res. 2010;70:6957-67 pubmed publisher
    ..Specifically, the SCN5A gene encoding the VGSC isotype Na(v)1.5 has been defined as a key driver of human cancer cell invasion...
  5. Mann S, Castro M, Ohanian M, Guo G, Zodgekar P, Sheu A, et al. R222Q SCN5A mutation is associated with reversible ventricular ectopy and dilated cardiomyopathy. J Am Coll Cardiol. 2012;60:1566-73 pubmed publisher
    The goal of this study was to characterize a variant in the SCN5A gene that encodes the alpha-subunit of the cardiac sodium channel, Nav1...
  6. Kim J, Ghosh S, Liu H, Tateyama M, Kass R, Pitt G. Calmodulin mediates Ca2+ sensitivity of sodium channels. J Biol Chem. 2004;279:45004-12 pubmed
    ..Together, these data offer new biochemical evidence for Ca2+/CaM modulation of Na+ channel function. ..
  7. Paulussen A, Gilissen R, Armstrong M, Doevendans P, Verhasselt P, Smeets H, et al. Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl). 2004;82:182-8 pubmed
    ..Five cLQTS genes ( KCNH2, KCNQ1, SCN5A, KCNE1, KCNE2) were thoroughly screened for genetic variations in 32 drug-induced aLQTS patients with confirmed ..
  8. Zhang Y, Wang T, Ma A, Zhou X, Gui J, Wan H, et al. 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;194:311-23 pubmed publisher
    ..Full clinical evaluation of pedigree members through three generations of a Chinese family combined with SCN5A sequencing from genomic DNA was compared with patch and voltage-clamp results from two independent expression ..
  9. Schulze Bahr E, Eckardt L, Breithardt G, Seidl K, Wichter T, Wolpert C, et al. Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: different incidences in familial and sporadic disease. Hum Mutat. 2003;21:651-2 pubmed
    ..Mutations in the cardiac sodium channel gene SCN5A are only known to cause BS...
  10. Tan B, Iturralde Torres P, Medeiros Domingo A, Nava S, Tester D, Valdivia C, et al. A novel C-terminal truncation SCN5A mutation from a patient with sick sinus syndrome, conduction disorder and ventricular tachycardia. Cardiovasc Res. 2007;76:409-17 pubmed
    Individual mutations in the SCN5A-encoding cardiac sodium channel alpha-subunit cause single cardiac arrhythmia disorders, but a few cause multiple distinct disorders...
  11. Takahata T, Yasui Furukori N, Sasaki S, Igarashi T, Okumura K, Munakata A, et al. Nucleotide changes in the translated region of SCN5A from Japanese patients with Brugada syndrome and control subjects. Life Sci. 2003;72:2391-9 pubmed
    The mutations of the SCN5A gene have been implicated to play a pathogenetic role in Brugada syndrome, which causes ventricular fibrillation...
  12. Splawski I, Timothy K, Tateyama M, Clancy C, Malhotra A, Beggs A, et al. Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. Science. 2002;297:1333-6 pubmed
    ..We identified a variant of the cardiac sodium channel gene SCN5A that is associated with arrhythmia in African Americans (P = 0...
  13. Keller D, Acharfi S, Delacretaz E, Benammar N, Rotter M, Pfammatter J, et al. A novel mutation in SCN5A, delQKP 1507-1509, causing long QT syndrome: role of Q1507 residue in sodium channel inactivation. J Mol Cell Cardiol. 2003;35:1513-21 pubmed
    Inherited long QT syndrome (LQTS) is caused by mutations in six genes including SCN5A, encoding the alpha-subunit of the human cardiac voltage-dependent sodium channel hNa(v)1.5...
  14. Sheets M, Hanck D. Outward stabilization of the S4 segments in domains III and IV enhances lidocaine block of sodium channels. J Physiol. 2007;582:317-34 pubmed
    ..We conclude that the positions of the S4s in domains III and IV are major determinants of the voltage dependence of lidocaine affinity. ..
  15. Onkal R, Mattis J, Fraser S, Diss J, Shao D, Okuse K, et al. Alternative splicing of Nav1.5: an electrophysiological comparison of 'neonatal' and 'adult' isoforms and critical involvement of a lysine residue. J Cell Physiol. 2008;216:716-26 pubmed publisher
    ..5 would (1) modify the channel kinetics and (2) prolong the resultant current, allowing greater intracellular Na(+) influx. Developmental and pathophysiological consequences of such differences are discussed. ..
  16. Wilde A, Brugada R. Phenotypical manifestations of mutations in the genes encoding subunits of the cardiac sodium channel. Circ Res. 2011;108:884-97 pubmed publisher
    Variations in the gene encoding for the major sodium channel (Na(v)1.5) in the heart, SCN5A, has been shown to cause a number of arrhythmia syndromes (with or without structural changes in the myocardium), including the long-QT syndrome (..
  17. Makielski J, Ye B, Valdivia C, Pagel M, Pu J, Tester D, et al. A ubiquitous splice variant and a common polymorphism affect heterologous expression of recombinant human SCN5A heart sodium channels. Circ Res. 2003;93:821-8 pubmed
    Amino acid sequence variations in SCN5A are known to affect function of wild-type channels and also those with coexisting mutations; therefore, it is important to know the exact sequence and function of channels most commonly present in ..
  18. Tester D, Will M, Haglund C, Ackerman M. Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005;2:507-17 pubmed
    ..A cardiac channel gene screen for LQTS-causing mutations in KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6) was performed for 541 consecutive, unrelated patients (358 females, average ..
  19. Smits J, Eckardt L, Probst V, Bezzina C, Schott J, Remme C, et al. Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. J Am Coll Cardiol. 2002;40:350-6 pubmed
    ..with (carriers) and those without (non-carriers) a mutation in the gene encoding the cardiac sodium channel (SCN5A) using clinical parameters...
  20. Olson T, Michels V, Ballew J, Reyna S, Karst M, Herron K, et al. Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA. 2005;293:447-54 pubmed
    ..Correlation of identified mutations with cardiac phenotype. Refined locus mapping revealed SCN5A, encoding the cardiac sodium channel, as a candidate gene...
  21. Petitprez S, Jespersen T, Pruvot E, Keller D, Corbaz C, Schlapfer J, et al. Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome. Cardiovasc Res. 2008;78:494-504 pubmed publisher
    ..BrS is caused, in part, by mutations in the SCN5A gene, which encodes the sodium channel alpha-subunit Na(v)1.5...
  22. Remme C, Wilde A, Bezzina C. Cardiac sodium channel overlap syndromes: different faces of SCN5A mutations. Trends Cardiovasc Med. 2008;18:78-87 pubmed publisher
    Cardiac sodium channel dysfunction caused by mutations in the SCN5A gene is associated with a number of relatively uncommon arrhythmia syndromes, including long-QT syndrome type 3 (LQT3), Brugada syndrome, conduction disease, sinus node ..
  23. Camacho J, Hensellek S, Rougier J, Blechschmidt S, Abriel H, Benndorf K, et al. Modulation of Nav1.5 channel function by an alternatively spliced sequence in the DII/DIII linker region. J Biol Chem. 2006;281:9498-506 pubmed
    ..Moreover, the present study identified novel short sequence motifs within this amphiphilic region that specifically affect the voltage dependence of steady-state activation and inactivation and current amplitude of human Na(v)1.5. ..
  24. Kapplinger J, Tester D, Alders M, Benito B, Berthet M, Brugada J, et al. An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2010;7:33-46 pubmed publisher
    Brugada syndrome (BrS) is a common heritable channelopathy. Mutations in the SCN5A-encoded sodium channel (BrS1) culminate in the most common genotype...
  25. Meregalli P, Tan H, Probst V, Koopmann T, Tanck M, Bhuiyan Z, et al. Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. Heart Rhythm. 2009;6:341-8 pubmed publisher
    Patients carrying loss-of-function SCN5A mutations linked to Brugada syndrome (BrS) or progressive cardiac conduction disease (PCCD) are at risk of sudden cardiac death at a young age...
  26. Ruan Y, Denegri M, Liu N, Bachetti T, Seregni M, Morotti S, et al. Trafficking defects and gating abnormalities of a novel SCN5A mutation question gene-specific therapy in long QT syndrome type 3. Circ Res. 2010;106:1374-83 pubmed publisher gene-specific treatments in long-QT syndrome type 3, which is caused by mutations in the sodium channel gene (SCN5A). Response to treatment is influenced by biophysical properties of mutations...
  27. Wang C, Chung B, Yan H, Lee S, Pitt G. Crystal structure of the ternary complex of a NaV C-terminal domain, a fibroblast growth factor homologous factor, and calmodulin. Structure. 2012;20:1167-76 pubmed publisher
    ..Furthermore, we identify a critical interaction that contributes to the specificity of individual Na(V) CTD isoforms for distinctive FHFs. ..
  28. Chen T, Inoue M, Sheets M. Reduced voltage dependence of inactivation in the SCN5A sodium channel mutation delF1617. Am J Physiol Heart Circ Physiol. 2005;288:H2666-76 pubmed domain IV of the human heart Na(+) channel (hH1a) has been tentatively associated with long QT syndrome type 3 (LQT3)...
  29. Ellinor P, Nam E, Shea M, Milan D, Ruskin J, Macrae C. Cardiac sodium channel mutation in atrial fibrillation. Heart Rhythm. 2008;5:99-105 pubmed
    Mutations in the sodium channel SCN5A have been implicated in many cardiac disorders, including the long QT syndrome, Brugada syndrome, conduction system disease, and dilated cardiomyopathy with atrial arrhythmias...
  30. Marangoni S, Di Resta C, Rocchetti M, Barile L, Rizzetto R, Summa A, et al. A Brugada syndrome mutation (p.S216L) and its modulation by p.H558R polymorphism: standard and dynamic characterization. Cardiovasc Res. 2011;91:606-16 pubmed publisher
    The Na(+) channel mutation (p.S216L), previously associated with type 3 long-QT syndrome (LQT3) phenotype, and a common polymorphism (p.H558R) were detected in a patient with an intermittent Brugada syndrome (BS) ECG pattern...
  31. Wu L, Yong S, Fan C, Ni Y, Yoo S, Zhang T, et al. Identification of a new co-factor, MOG1, required for the full function of cardiac sodium channel Nav 1.5. J Biol Chem. 2008;283:6968-78 pubmed publisher
    ..This study further demonstrates the functional diversity of Nav1.5-binding proteins, which serve important functions for Nav1.5 under different cellular conditions. ..
  32. Pfeufer A, Sanna S, Arking D, Müller M, Gateva V, Fuchsberger C, et al. Common variants at ten loci modulate the QT interval duration in the QTSCD Study. Nat Genet. 2009;41:407-14 pubmed publisher
    ..Four loci map near the monogenic long-QT syndrome genes KCNQ1, KCNH2, SCN5A and KCNJ2...
  33. Fraser S, Diss J, Chioni A, Mycielska M, Pan H, Yamaci R, et al. Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clin Cancer Res. 2005;11:5381-9 pubmed
    ..Up-regulation of neonatal Na(v)1.5 occurs as an integral part of the metastatic process in human breast cancer and could serve both as a novel marker of the metastatic phenotype and a therapeutic target. ..
  34. Shin D, Kim E, Park S, Jang W, Bae Y, Han J, et al. A novel mutation in the SCN5A gene is associated with Brugada syndrome. Life Sci. 2007;80:716-24 pubmed
    ..inherited cardiac disorder associated with a high risk of sudden cardiac death and is caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha-subunit (Na(v)1.5)...
  35. Casini S, Tan H, Bhuiyan Z, Bezzina C, Barnett P, Cerbai E, et al. Characterization of a novel SCN5A mutation associated with Brugada syndrome reveals involvement of DIIIS4-S5 linker in slow inactivation. Cardiovasc Res. 2007;76:418-29 pubmed
    Mutations in SCN5A, the gene encoding the alpha-subunit of the cardiac sodium channel (Na(v)1.5), have been associated with various inherited arrhythmia syndromes, including Brugada syndrome (BrS)...
  36. Sarhan M, Van Petegem F, Ahern C. A double tyrosine motif in the cardiac sodium channel domain III-IV linker couples calcium-dependent calmodulin binding to inactivation gating. J Biol Chem. 2009;284:33265-74 pubmed publisher
    ..The results demonstrate that calcium-dependent calmodulin binding to the sodium channel inactivation gate double tyrosine motif is required for calcium regulation of the cardiac sodium channel. ..
  37. Hu D, Barajas Martinez H, Nesterenko V, Pfeiffer R, Guerchicoff A, Cordeiro J, et al. Dual variation in SCN5A and CACNB2b underlies the development of cardiac conduction disease without Brugada syndrome. Pacing Clin Electrophysiol. 2010;33:274-85 pubmed publisher
    Inherited loss of function mutations in SCN5A have been linked to overlapping syndromes including cardiac conduction disease and Brugada syndrome (BrS)...
  38. Chevalier P, Bellocq C, Millat G, Piqueras E, Potet F, Schott J, et al. Torsades de pointes complicating atrioventricular block: evidence for a genetic predisposition. Heart Rhythm. 2007;4:170-4 pubmed
    ..Genetic studies screening for HERG, KCNQ1 KCNE1, KCNE2, and SCN5A mutations were performed...
  39. Surber R, Hensellek S, Prochnau D, Werner G, Benndorf K, Figulla H, et al. Combination of cardiac conduction disease and long QT syndrome caused by mutation T1620K in the cardiac sodium channel. Cardiovasc Res. 2008;77:740-8 pubmed
    ..mechanism underlying the concomitant occurrence of cardiac conduction disease and long QT syndrome (LQT3), two SCN5A channelopathies that are explained by loss-of-function and gain-of-function, respectively, in the cardiac Na+ ..
  40. Rook M, Evers M, Vos M, Bierhuizen M. Biology of cardiac sodium channel Nav1.5 expression. Cardiovasc Res. 2012;93:12-23 pubmed publisher
    ..Mutations in the gene-encoding Na(v)1.5, SCN5A, have been associated with a variety of arrhythmic disorders, including long QT, Brugada, and sick sinus syndromes ..
  41. Núñez L, Barana A, Amorós I, de la Fuente M, Dolz Gaiton P, Gomez R, et al. p.D1690N Nav1.5 rescues p.G1748D mutation gating defects in a compound heterozygous Brugada syndrome patient. Heart Rhythm. 2013;10:264-72 pubmed publisher
    We identified 2 compound heterozygous mutations (p.D1690N and p.G1748D) in the SCN5A gene encoding cardiac Na(+) channels (Nav1.5) in a proband diagnosed with Brugada syndrome type 1. Furthermore, in the allele encoding the p...
  42. Makita N, Sasaki K, Groenewegen W, Yokota T, Yokoshiki H, Murakami T, et al. Congenital atrial standstill associated with coinheritance of a novel SCN5A mutation and connexin 40 polymorphisms. Heart Rhythm. 2005;2:1128-34 pubmed
    Congenital atrial standstill has been linked to SCN5A. Incomplete penetrance observed in atrial standstill has been attributed in part to the digenic inheritance of polymorphisms in the atrial-specific gap junction connexin 40 (Cx40) in ..
  43. Napolitano C, Priori S, Schwartz P, Bloise R, Ronchetti E, Nastoli J, et al. Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005;294:2975-80 pubmed
    ..We investigated whether the detection of a set of frequently mutated codons in the KCNQ1, KCNH2, and SCN5A genes may translate in a novel strategy for rapid efficient genetic testing of 430 consecutive patients referred ..
  44. Shah V, Wingo T, Weiss K, Williams C, Balser J, Chazin W. Calcium-dependent regulation of the voltage-gated sodium channel hH1: intrinsic and extrinsic sensors use a common molecular switch. Proc Natl Acad Sci U S A. 2006;103:3592-7 pubmed
    The function of the human cardiac voltage-gated sodium channel Na(V)1.5 (hH1) is regulated in part by binding of calcium to an EF hand in the C-terminal cytoplasmic domain...
  45. Wolf C, Berul C. Inherited conduction system abnormalities--one group of diseases, many genes. J Cardiovasc Electrophysiol. 2006;17:446-55 pubmed
    ..Human genetic studies have identified mutations in the sodium channel SCN5A gene causing tachyarrhythmia disorders, as well as progressive cardiac conduction system diseases, or overlapping ..
  46. Otagiri T, Kijima K, Osawa M, Ishii K, Makita N, Matoba R, et al. Cardiac ion channel gene mutations in sudden infant death syndrome. Pediatr Res. 2008;64:482-7 pubmed publisher
    ..genes causing long QT syndrome in 42 Japanese SIDS victims and found five mutations, KCNQ1-K598R, KCNH2-T895M, SCN5A-F532C, SCN5A-G1084S, and SCN5A-F1705S, in four cases; one case had both KCNH2-T895M and SCN5A-G1084S...
  47. Bankston J, Sampson K, Kateriya S, Glaaser I, Malito D, Chung W, et al. A novel LQT-3 mutation disrupts an inactivation gate complex with distinct rate-dependent phenotypic consequences. Channels (Austin). 2007;1:273-80 pubmed
    Inherited mutations of SCN5A, the gene that encodes Na(V)1.5, the alpha subunit of the principle voltage-gated Na(+) channel in the heart, cause congenital Long QT Syndrome variant 3 (LQT-3) by perturbation of channel inactivation...
  48. Lizotte E, Junttila M, Dube M, Hong K, Benito B, De Zutter M, et al. Genetic modulation of brugada syndrome by a common polymorphism. J Cardiovasc Electrophysiol. 2009;20:1137-41 pubmed publisher
    Brugada syndrome predisposes some subjects to ventricular tachyarrhythmias and sudden cardiac death. Mutations in SCN5A gene have been associated with approximately 25% of Brugada syndrome patients...
  49. Leoni A, Gavillet B, Rougier J, Marionneau C, Probst V, Le Scouarnec S, et al. Variable Na(v)1.5 protein expression from the wild-type allele correlates with the penetrance of cardiac conduction disease in the Scn5a(+/-) mouse model. PLoS ONE. 2010;5:e9298 pubmed publisher
    Loss-of-function mutations in SCN5A, the gene encoding Na(v)1.5 Na+ channel, are associated with inherited cardiac conduction defects and Brugada syndrome, which both exhibit variable phenotypic penetrance of conduction defects...
  50. Gao R, Shen Y, Cai J, Lei M, Wang Z. Expression of voltage-gated sodium channel alpha subunit in human ovarian cancer. Oncol Rep. 2010;23:1293-9 pubmed
    ..Our findings suggested that abnormal expression of Nav1.5 could be an integral component of the metastatic process in human ovarian cancer and might serve as a therapeutic target in ovarian cancer treatment. ..
  51. Olesen M, Yuan L, Liang B, Holst A, Nielsen N, Nielsen J, et al. High prevalence of long QT syndrome-associated SCN5A variants in patients with early-onset lone atrial fibrillation. Circ Cardiovasc Genet. 2012;5:450-9 pubmed publisher
    ..We hypothesized that early-onset lone AF was associated with genetic variation in SCN5A. The coding sequence of SCN5A was sequenced in 192 patients with early-onset lone AF...
  52. Ishikawa T, Takahashi N, Ohno S, Sakurada H, Nakamura K, On Y, et al. Novel SCN3B mutation associated with brugada syndrome affects intracellular trafficking and function of Nav1.5. Circ J. 2013;77:959-67 pubmed
    ..The major causes of BrS are mutations in SCN5A for a large subunit of the sodium channel, Nav1...
  53. Tarradas A, Selga E, Beltran Alvarez P, Pérez Serra A, Riuró H, Picó F, et al. A novel missense mutation, I890T, in the pore region of cardiac sodium channel causes Brugada syndrome. PLoS ONE. 2013;8:e53220 pubmed publisher
    ..BrS) is a life-threatening, inherited arrhythmogenic syndrome associated with autosomal dominant mutations in SCN5A, the gene encoding the cardiac Na(+) channel alpha subunit (Na(v)1.5)...
  54. McNair W, Ku L, Taylor M, Fain P, Dao D, Wolfel E, et al. SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation. 2004;110:2163-7 pubmed
    ..Previous linkage analysis mapped the disease phenotype to a 30-cM region on chromosome 3p22-p25 (CMD1E)...
  55. Tan B, Valdivia C, Song C, Makielski J. Partial expression defect for the SCN5A missense mutation G1406R depends on splice variant background Q1077 and rescue by mexiletine. Am J Physiol Heart Circ Physiol. 2006;291:H1822-8 pubmed
    Mutations in the cardiac Na(+) channel gene SCN5A cause loss of function and underlie arrhythmia syndromes. SCN5A in humans has two splice variants, one lacking a glutamine at position 1077 (Q1077del) and one containing Q1077...
  56. Cordeiro J, Barajas Martinez H, Hong K, Burashnikov E, Pfeiffer R, Orsino A, et al. Compound heterozygous mutations P336L and I1660V in the human cardiac sodium channel associated with the Brugada syndrome. Circulation. 2006;114:2026-33 pubmed
    Loss-of-function mutations in SCN5A have been associated with the Brugada syndrome. We report the first Brugada syndrome family with compound heterozygous mutations in SCN5A...
  57. Wang D, Desai R, Crotti L, Arnestad M, Insolia R, Pedrazzini M, et al. Cardiac sodium channel dysfunction in sudden infant death syndrome. Circulation. 2007;115:368-76 pubmed
    Mutations in genes responsible for the congenital long-QT syndrome, especially SCN5A, have been identified in some cases of sudden infant death syndrome...
  58. London B, Michalec M, Mehdi H, Zhu X, Kerchner L, Sanyal S, et al. Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Circulation. 2007;116:2260-8 pubmed
    ..Mutations in the cardiac Na+ channel SCN5A on chromosome 3p21 cause approximately 20% of the cases of Brugada syndrome; most mutations decrease inward Na+ ..
  59. Hsueh C, Chen W, Lin J, Tsai C, Liu Y, Juang J, et al. Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations. J Biomed Sci. 2009;16:23 pubmed publisher
    ..The molecular and cellular mechanisms that lead to Brugada syndrome are not yet completely understood. However, SCN5A is the most well known responsible gene that causes Brugada syndrome...
  60. Casini S, Tan H, Demirayak I, Remme C, Amin A, Scicluna B, et al. Tubulin polymerization modifies cardiac sodium channel expression and gating. Cardiovasc Res. 2010;85:691-700 pubmed publisher
    ..Human embryonic kidney (HEK293) cells, transfected with SCN5A cDNA alone (Na(v)1.5) or together with SCN1B cDNA (Na(v)1...
  61. Albert C, Macrae C, Chasman D, VanDenburgh M, Buring J, Manson J, et al. Common variants in cardiac ion channel genes are associated with sudden cardiac death. Circ Arrhythm Electrophysiol. 2010;3:222-9 pubmed publisher
    ..SNPs associated with QT interval duration, and 5 nonsynonymous SNPs) in 5 cardiac ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2, and sudden and/or arrhythmic death in a combined nested case-control analysis among 516 cases ..
  62. Nair K, Pekhletski R, Harris L, Care M, Morel C, Farid T, et al. Escape capture bigeminy: phenotypic marker of cardiac sodium channel voltage sensor mutation R222Q. Heart Rhythm. 2012;9:1681-1688.e1 pubmed publisher
    ..Genetic analysis of 3 family members revealed the same mutation (R222Q) in the cardiac sodium channel gene, SCN5A (nucleotide change was 665 G?A that led to missense amino acid substitution Arg 222 Gln, located in the S4 voltage ..
  63. Clatot J, Ziyadeh Isleem A, Maugenre S, Denjoy I, Liu H, Dilanian G, et al. Dominant-negative effect of SCN5A N-terminal mutations through the interaction of Na(v)1.5 ?-subunits. Cardiovasc Res. 2012;96:53-63 pubmed publisher
    ..b>SCN5A, encoding the cardiac sodium channel Na(v)1.5, is the main gene involved in BrS...
  64. Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, et al. Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization. Circ Arrhythm Electrophysiol. 2011;4:874-81 pubmed publisher
    ..We identified nonsynonymous variants in SCN5A (resulting in A226D, L846R, and R367H) in 3 unrelated patients...
  65. Groenewegen W, Firouzi M, Bezzina C, Vliex S, van Langen I, Sandkuijl L, et al. A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill. Circ Res. 2003;92:14-22 pubmed
    ..Candidate gene screening revealed a novel mutation in the cardiac sodium channel gene SCN5A (D1275N) in all three affected living relatives and in five unaffected relatives, and the deceased relative was an ..
  66. Zimmer T, Surber R. SCN5A channelopathies--an update on mutations and mechanisms. Prog Biophys Mol Biol. 2008;98:120-36 pubmed publisher
    ..Na(v)1.5, encoded by the SCN5A gene, is the predominant isoform in the heart...
  67. Benson D, Wang D, Dyment M, Knilans T, Fish F, Strieper M, et al. Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest. 2003;112:1019-28 pubmed
    ..with disorders of cardiac rhythm and conduction, we screened the alpha subunit of the cardiac sodium channel (SCN5A) as a candidate gene in ten pediatric patients from seven families who were diagnosed with congenital SSS during ..
  68. Ou S, Kameyama A, Hao L, Horiuchi M, Minobe E, Wang W, et al. Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCN5A. Eur J Neurosci. 2005;22:793-801 pubmed
    ..Sequence analysis has indicated that hNbR1 is highly homologous with human cardiac Nav1.5/SCN5A with > 99% amino acid identity...
  69. Makiyama T, Akao M, Tsuji K, Doi T, Ohno S, Takenaka K, et al. High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations. J Am Coll Cardiol. 2005;46:2100-6 pubmed
    We carried out a complete screening of the SCN5A gene in 38 Japanese patients with Brugada syndrome to investigate the genotype-phenotype relationship...
  70. Plant L, Bowers P, Liu Q, Morgan T, Zhang T, State M, et al. A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y. J Clin Invest. 2006;116:430-5 pubmed
    ..While 2 cases have been associated with mutations in type Valpha, cardiac voltage-gated sodium channels (SCN5A), the "Back to Sleep" campaign has decreased SIDS prevalence, consistent with a role for environmental ..
  71. Gavillet B, Rougier J, Domenighetti A, Behar R, Boixel C, Ruchat P, et al. Cardiac sodium channel Nav1.5 is regulated by a multiprotein complex composed of syntrophins and dystrophin. Circ Res. 2006;99:407-14 pubmed
    ..5. In the absence of dystrophin, decreased sodium current may explain the alterations in cardiac conduction observed in patients with dystrophinopathies. ..
  72. Poelzing S, Forleo C, Samodell M, Dudash L, Sorrentino S, Anaclerio M, et al. SCN5A polymorphism restores trafficking of a Brugada syndrome mutation on a separate gene. Circulation. 2006;114:368-76 pubmed
    ..Previously, the R282H-SCN5A mutation in the sodium channel gene was identified in patients with Brugada syndrome...
  73. Darbar D, Kannankeril P, Donahue B, Kucera G, Stubblefield T, Haines J, et al. Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. Circulation. 2008;117:1927-35 pubmed publisher
    ..Here, we tested the hypothesis that vulnerability to AF is associated with variation in SCN5A, the gene encoding the cardiac sodium channel...
  74. Potet F, Chagot B, Anghelescu M, Viswanathan P, Stepanovic S, Kupershmidt S, et al. Functional Interactions between Distinct Sodium Channel Cytoplasmic Domains through the Action of Calmodulin. J Biol Chem. 2009;284:8846-54 pubmed publisher
    ..These findings have bearing upon Na(+) channel function in genetically altered channels and under pathophysiologic conditions where [Ca(2+)](i) impacts cardiac conduction. ..
  75. Probst V, Wilde A, Barc J, Sacher F, Babuty D, Mabo P, et al. SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome. Circ Cardiovasc Genet. 2009;2:552-7 pubmed publisher
    Mutations in SCN5A are identified in approximately 20% to 30% of probands affected by Brugada syndrome (BrS). However, in familial studies, the relationship between SCN5A mutations and BrS remains poorly understood...
  76. Chagot B, Chazin W. Solution NMR structure of Apo-calmodulin in complex with the IQ motif of human cardiac sodium channel NaV1.5. J Mol Biol. 2011;406:106-19 pubmed publisher
    ..The structure also provides insight into the biochemical basis for disease-associated mutations that map to the IQ motif in Na(V)1.5. ..
  77. Ackerman M, Splawski I, Makielski J, Tester D, Will M, Timothy K, et al. Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing. Heart Rhythm. 2004;1:600-7 pubmed
    ..Pathogenic mutations in the cardiac sodium channel gene, SCN5A, cause approximately 15 to 20% of Brugada syndrome (BrS1), 5 to 10% of long QT syndrome (LQT3), and 2 to 5% of ..
  78. Smits J, Koopmann T, Wilders R, Veldkamp M, Opthof T, Bhuiyan Z, et al. A mutation in the human cardiac sodium channel (E161K) contributes to sick sinus syndrome, conduction disease and Brugada syndrome in two families. J Mol Cell Cardiol. 2005;38:969-81 pubmed
    Mutations in the gene encoding the human cardiac sodium channel (SCN5A) have been associated with three distinct cardiac arrhythmia disorders: the long QT syndrome, the Brugada syndrome and cardiac conduction disease...
  79. Bezzina C, Shimizu W, Yang P, Koopmann T, Tanck M, Miyamoto Y, et al. Common sodium channel promoter haplotype in asian subjects underlies variability in cardiac conduction. Circulation. 2006;113:338-44 pubmed
    ..Loss of function mutations in SCN5A, encoding the cardiac sodium channel, are one cause of the Brugada syndrome, associated with slow conduction and a ..
  80. Keller D, Huang H, Zhao J, Frank R, Suarez V, Delacretaz E, et al. A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation. Cardiovasc Res. 2006;70:521-9 pubmed
    ..About 20% of patients have mutations in the only so far identified gene, SCN5A, which encodes the alpha-subunit of the human cardiac voltage-dependent sodium channel (hNa(v)1.5)...
  81. Arnestad M, Crotti L, Rognum T, Insolia R, Pedrazzini M, Ferrandi C, et al. Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation. 2007;115:361-7 pubmed
    ..Molecular screening of 7 genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CAV3) associated with LQTS was performed with denaturing high-performance liquid ..
  82. Makita N, Behr E, Shimizu W, Horie M, Sunami A, Crotti L, et al. The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome. J Clin Invest. 2008;118:2219-29 pubmed publisher
    ..3 long QT syndrome (LQT3) with Brugada syndrome (BrS) is observed in some carriers of mutations in the Na channel SCN5A. While this overlap is important for patient management, the clinical features, prevalence, and mechanisms ..
  83. Bebarova M, O Hara T, Geelen J, Jongbloed R, Timmermans C, Arens Y, et al. 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;295:H48-58 pubmed publisher
    ..with a Na(+) current (I(Na)) loss-of-function mutation from studies in a Dutch kindred with the COOH-terminal SCN5A variant p.Phe2004Leu...
  84. Newton Cheh C, Eijgelsheim M, Rice K, de Bakker P, Yin X, Estrada K, et al. Common variants at ten loci influence QT interval duration in the QTGEN Study. Nat Genet. 2009;41:399-406 pubmed publisher
    ..We observed associations at P < 5 x 10(-8) with variants in NOS1AP, KCNQ1, KCNE1, KCNH2 and SCN5A, known to be involved in myocardial repolarization and mendelian long-QT syndromes...
  85. Gui J, Wang T, Trump D, Zimmer T, Lei M. Mutation-specific effects of polymorphism H558R in SCN5A-related sick sinus syndrome. J Cardiovasc Electrophysiol. 2010;21:564-73 pubmed publisher
    Mutations in SCN5A, the gene encoding alpha subunit of cardiac type sodium channel, Na(v)1.5, lead to familial sick sinus syndrome (SSS)...
  86. Brisson L, Driffort V, Benoist L, Poet M, Counillon L, Antelmi E, et al. NaV1.5 Na? channels allosterically regulate the NHE-1 exchanger and promote the activity of breast cancer cell invadopodia. J Cell Sci. 2013;126:4835-42 pubmed publisher
    ..NaV1.5 (also known as SCN5A) Na(+) channels are overexpressed in breast cancer tumours and are associated with metastatic occurrence...
  87. Mohler P, Rivolta I, Napolitano C, LeMaillet G, Lambert S, Priori S, et al. 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;101:17533-8 pubmed
    ..Together with previous work in neurons, these results in cardiomyocytes suggest that ankyrin-G participates in a common pathway for localization of voltage-gated Na(v) channels at sites of function in multiple excitable cell types. ..
  88. Itoh H, Shimizu M, Mabuchi H, Imoto K. Clinical and electrophysiological characteristics of Brugada syndrome caused by a missense mutation in the S5-pore site of SCN5A. J Cardiovasc Electrophysiol. 2005;16:378-83 pubmed
    Brugada syndrome is an inherited cardiac disorder caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha-subunit, and potentially leads to ventricular fibrillation and sudden death...
  89. Burke A, Creighton W, Mont E, Li L, Hogan S, Kutys R, et al. Role of SCN5A Y1102 polymorphism in sudden cardiac death in blacks. Circulation. 2005;112:798-802 pubmed
    The Y1102 polymorphism of the cardiac sodium channel (SCN5A) gene has been found in 13% of black Americans. It has been linked to lethal arrhythmias in black families with ventricular tachycardia...
  90. Frustaci A, Priori S, Pieroni M, Chimenti C, Napolitano C, Rivolta I, et al. Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation. 2005;112:3680-7 pubmed
    ..coronary and ventricular angiography, biventricular endomyocardial biopsy, and DNA screening of the SCN5A gene. Biopsy samples were processed for histology, electron microscopy, and molecular screening for viral genomes...
  91. Mank Seymour A, Richmond J, Wood L, Reynolds J, Fan Y, Warnes G, et al. Association of torsades de pointes with novel and known single nucleotide polymorphisms in long QT syndrome genes. Am Heart J. 2006;152:1116-22 pubmed
    ..Six novel mutations--4 in ANK2, 1 in KCNQ1, and 1 in SCN5A--were found in the patients with TdP...
  92. Van Norstrand D, Tester D, Ackerman M. Overrepresentation of the proarrhythmic, sudden death predisposing sodium channel polymorphism S1103Y in a population-based cohort of African-American sudden infant death syndrome. Heart Rhythm. 2008;5:712-5 pubmed publisher
    The S1103Y-SCN5A polymorphism has been implicated as a proarrhythmic, sudden death predisposing risk factor in African Americans, including one postmortem investigation of African-American infants with sudden infant death syndrome (SIDS)...