Gene Symbol: SCN4B
Description: sodium voltage-gated channel beta subunit 4
Alias: ATFB17, LQT10, Navbeta4, sodium channel subunit beta-4, sodium channel, voltage-gated, type IV, beta subunit
Species: human
Products:     SCN4B

Top Publications

  1. Yu F, Westenbroek R, Silos Santiago I, McCormick K, Lawson D, Ge P, et al. Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2. J Neurosci. 2003;23:7577-85 pubmed
    ..This novel, disulfide-linked beta subunit is likely to affect both protein-protein interactions and physiological function of multiple sodium channel alpha subunits. ..
  2. Yang Q, Xiong H, Xu C, Huang Y, Tu X, Wu G, et al. Identification of rare variants in cardiac sodium channel β4-subunit gene SCN4B associated with ventricular tachycardia. Mol Genet Genomics. 2019;: pubmed publisher
    ..Ventricular tachycardia (VT) causes sudden cardiac death, however, the majority of risk genes for VT remain unknown. SCN4B encodes a β-subunit, Navβ4, for the voltage-gated cardiac sodium channel complex involved in ..
  3. Lewis A, Raman I. Resurgent current of voltage-gated Na(+) channels. J Physiol. 2014;592:4825-38 pubmed publisher
    ..of resurgent current depends on a factor in the Na(+) channel complex, probably a subunit such as NaVβ4 (Scn4b), which blocks open Na(+) channels at positive voltages, competing with the fast inactivation gate, and unblocks ..
  4. Lee Y, Shin D, Song K. Dominance effects of ion transport and ion transport regulator genes on the final weight and backfat thickness of Landrace pigs by dominance deviation analysis. Genes Genomics. 2018;40:1331-1338 pubmed publisher
    ..the backfat thickness were the regulation of ion transport with the STAC, GCK, TRPC6, UBASH3B, CAMK2D, CACNG4 and SCN4B genes...
  5. Miyazaki H, Oyama F, Inoue R, Aosaki T, Abe T, Kiyonari H, et al. Singular localization of sodium channel β4 subunit in unmyelinated fibres and its role in the striatum. Nat Commun. 2014;5:5525 pubmed publisher
    ..b>Scn4b-deficient mice show a resurgent Na(+) current reduction, decreased repetitive firing frequency in medium spiny ..
  6. Allegue C, Coll M, Mates J, Campuzano O, Iglesias A, Sobrino B, et al. Genetic Analysis of Arrhythmogenic Diseases in the Era of NGS: The Complexity of Clinical Decision-Making in Brugada Syndrome. PLoS ONE. 2015;10:e0133037 pubmed publisher
  7. Stein A, Goonewardena S, Jones T, Prusick P, Bazzi A, Belyavskaya J, et al. The PTIP-Associated Histone Methyltransferase Complex Prevents Stress-Induced Maladaptive Cardiac Remodeling. PLoS ONE. 2015;10:e0127839 pubmed publisher
    ..stress-induced gene expression profiles including blunted expression of ADRA1A, ADRA1B, JUN, ATP2A2, ATP1A2, SCN4B, and CACNA1G...
  8. Bon E, Driffort V, Gradek F, Martinez Caceres C, Anchelin M, Pelegrin P, et al. SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer. Nat Commun. 2016;7:13648 pubmed publisher
    ..Here we show that the SCN4B gene, encoding for the ?4 protein, initially characterized as an auxiliary subunit of voltage-gated sodium ..
  9. Gregers E, Ahlberg G, Christensen T, Jabbari J, Larsen K, Herfelt C, et al. Deep sequencing of atrial fibrillation patients with mitral valve regurgitation shows no evidence of mosaicism but reveals novel rare germline variants. Heart Rhythm. 2017;14:1531-1538 pubmed publisher
    ..We identified rare variants in genes never directly associated with AF: KCNE4, SCN4B, NEURL1, and CAND2. Interestingly, 7 patients (16%) had variants in genes involved in cellular potassium handling...

More Information


  1. Kim K, Liu J, Sells Galvin R, Dage J, Egeland J, Smith R, et al. Transcriptomic Analysis of Induced Pluripotent Stem Cells Derived from Patients with Bipolar Disorder from an Old Order Amish Pedigree. PLoS ONE. 2015;10:e0142693 pubmed publisher
    ..5 fold) and SCN4B, the voltage gated type IV sodium channel beta subunit (-14.6 fold)...
  2. Ransdell J, Dranoff E, Lau B, Lo W, Donermeyer D, Allen P, et al. Loss of Navβ4-Mediated Regulation of Sodium Currents in Adult Purkinje Neurons Disrupts Firing and Impairs Motor Coordination and Balance. Cell Rep. 2017;19:532-544 pubmed publisher
    ..To test these hypotheses, we examined the effects of the targeted deletion of Scn4b (Navβ4) on INaR and on repetitive firing in cerebellar Purkinje neurons...
  3. Takahara K, Yamamoto T, Uchida K, Zhu H, Shibata A, Inai T, et al. Effects of 4,9-anhydrotetrodotoxin on voltage-gated Na+ channels of mouse vas deferens myocytes and recombinant NaV1.6 channels. Naunyn Schmiedebergs Arch Pharmacol. 2018;391:489-499 pubmed publisher
    ..PCR showed that the expression of Scn1b was significantly higher than that of other β-subunit genes (Scn2b - Scn4b)...
  4. Olesen M, Jespersen T, Nielsen J, Liang B, Møller D, Hedley P, et al. Mutations in sodium channel ?-subunit SCN3B are associated with early-onset lone atrial fibrillation. Cardiovasc Res. 2011;89:786-93 pubmed publisher
    ..We tested the hypothesis that lone AF in young patients is associated with genetic mutations in SCN3B and SCN4B, the genes encoding the two ?-subunits of the cardiac sodium channel...
  5. Winkel B, Yuan L, Olesen M, Sadjadieh G, Wang Y, Risgaard B, et al. The role of the sodium current complex in a nonreferred nationwide cohort of sudden infant death syndrome. Heart Rhythm. 2015;12:1241-9 pubmed publisher
    ..5 channel complex: SCN5A, SCN1B, SCN2B, SCN3B, SCN4B, GPD1L, SNTA1, and CAV3. Patch-clamp analyses were performed on variants not previously characterized...
  6. Ji X, Saha S, Gao G, Lasek A, Homanics G, Guildford M, et al. The Sodium Channel ?4 Auxiliary Subunit Selectively Controls Long-Term Depression in Core Nucleus Accumbens Medium Spiny Neurons. Front Cell Neurosci. 2017;11:17 pubmed publisher
    ..Of particular interest is the ?4 subunit, encoded by the Scn4b gene, that is highly expressed in dorsal and ventral (i.e...
  7. Delgado P, García Zueco J, Rubio Felix D, Giralt M. [Idiopathic thrombocytopenic purpura: present knowledge and future expectations]. Sangre (Barc). 1992;37:449-56 pubmed
  8. Shimizu H, Tosaki A, Ohsawa N, Ishizuka Katsura Y, Shoji S, Miyazaki H, et al. Parallel homodimer structures of the extracellular domains of the voltage-gated sodium channel ?4 subunit explain its role in cell-cell adhesion. J Biol Chem. 2017;292:13428-13440 pubmed publisher
    ..These observations provide the structural basis for the parallel dimer formation of ?4 in VGSCs and reveal its mechanism in cell-cell adhesion. ..
  9. Bouza A, Isom L. Voltage-Gated Sodium Channel β Subunits and Their Related Diseases. Handb Exp Pharmacol. 2018;246:423-450 pubmed publisher
    ..Mutations in the β subunit genes (SCN1B-SCN4B) have been linked to a variety of diseases...
  10. Medeiros Domingo A, Kaku T, Tester D, Iturralde Torres P, Itty A, Ye B, et al. SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome. Circulation. 2007;116:134-42 pubmed
    ..and complete mutational analysis of the 4 Na(vbeta)-subunits revealed a L179F (C535T) missense mutation in SCN4B that cosegregated properly throughout a 3-generation pedigree and was absent in 800 reference alleles...
  11. Patel R, Barbosa C, Xiao Y, Cummins T. Human Nav1.6 Channels Generate Larger Resurgent Currents than Human Nav1.1 Channels, but the Navβ4 Peptide Does Not Protect Either Isoform from Use-Dependent Reduction. PLoS ONE. 2015;10:e0133485 pubmed publisher
    ..Overall, these two channels have distinct biophysical properties that may differentially contribute to regulating neuronal excitability. ..
  12. Peeters U, Scornik F, Riuró H, Pérez G, Komurcu Bayrak E, Van Malderen S, et al. Contribution of Cardiac Sodium Channel β-Subunit Variants to Brugada Syndrome. Circ J. 2015;79:2118-29 pubmed publisher
    ..TheSCN1B-SCN4B genes were screened, which encode the 5 sodium channel β-subunits, in a SCN5A negative BrS population (n=74)...
  13. Farris S, Arasappan D, Hunicke Smith S, Harris R, Mayfield R. Transcriptome organization for chronic alcohol abuse in human brain. Mol Psychiatry. 2015;20:1438-47 pubmed publisher
    ..For example, expression of a human-specific isoform of the voltage-gated sodium channel subunit SCN4B was significantly correlated to lifetime alcohol consumption...
  14. Gilchrist J, Das S, Van Petegem F, Bosmans F. Crystallographic insights into sodium-channel modulation by the ?4 subunit. Proc Natl Acad Sci U S A. 2013;110:E5016-24 pubmed publisher
  15. Li R, Wang Q, Xu Y, Zhang M, Qu X, Liu X, et al. Mutations of the SCN4B-encoded sodium channel ?4 subunit in familial atrial fibrillation. Int J Mol Med. 2013;32:144-50 pubmed publisher
    ..and SCN3B) have been associated with AF, which suggests that mutations in the sodium channel ?4 subunit gene, SCN4B, are also involved in the pathogenesis of AF...
  16. Tan B, Pundi K, Van Norstrand D, Valdivia C, Tester D, Medeiros Domingo A, et al. Sudden infant death syndrome-associated mutations in the sodium channel beta subunits. Heart Rhythm. 2010;7:771-8 pubmed publisher
    ..5 cardiac sodium channel. Recently, Na(V) beta subunits have been implicated in various cardiac arrhythmias. Thus, the 4 genes encoding Na(V) beta subunits represent plausible candidate genes for SIDS...
  17. Webb J, Wu F, Cannon S. Slow inactivation of the NaV1.4 sodium channel in mammalian cells is impeded by co-expression of the beta1 subunit. Pflugers Arch. 2009;457:1253-63 pubmed publisher
    ..Furthermore, the beta1 effect on slow inactivation was shown to be independent of the negative coupling between fast and slow inactivation. ..
  18. Lo W, Donermeyer D, Allen P. A voltage-gated sodium channel is essential for the positive selection of CD4(+) T cells. Nat Immunol. 2012;13:880-7 pubmed publisher
    ..Thus, active VGSCs in thymocytes provide a mechanism by which a weak positive selection signal can induce the sustained Ca(2+) signals required for CD4(+) T cell development. ..
  19. Theile J, Jarecki B, Piekarz A, Cummins T. Nav1.7 mutations associated with paroxysmal extreme pain disorder, but not erythromelalgia, enhance Navbeta4 peptide-mediated resurgent sodium currents. J Physiol. 2011;589:597-608 pubmed publisher
    ..This knowledge provides us with a better understanding of the mechanism of I(NaR) generation and may lead to the development of specialized treatment for pain disorders associated with I(NaR). ..
  20. Watanabe H, Darbar D, Kaiser D, Jiramongkolchai K, Chopra S, Donahue B, et al. Mutations in sodium channel ?1- and ?2-subunits associated with atrial fibrillation. Circ Arrhythm Electrophysiol. 2009;2:268-75 pubmed publisher
    ..We tested the hypothesis that mutations in the 4 sodium channel beta-subunit genes SCN1B-SCN4B contribute to AF susceptibility...