Gene Symbol: Scn2a
Description: sodium channel, voltage-gated, type II, alpha
Alias: 6430408L10, A230052E19Rik, Nav1.2, Scn2a1, sodium channel protein type 2 subunit alpha, sodium channel, voltage-gated, type II, alpha 1, sodium channel, voltage-gated, type II, alpha polypeptide 1, voltage-gated sodium channel Nav1.2 variant a, voltage-gated sodium channel Nav1.2 variant b
Species: mouse
Products:     Scn2a

Top Publications

  1. Kalume F, Yu F, Westenbroek R, Scheuer T, Catterall W. Reduced sodium current in Purkinje neurons from Nav1.1 mutant mice: implications for ataxia in severe myoclonic epilepsy in infancy. J Neurosci. 2007;27:11065-74 pubmed
    ..Loss of these channels in Purkinje neurons of mutant mice and SMEI patients may be sufficient to cause their ataxia and related functional deficits. ..
  2. Vega A, Henry D, Matthews G. Reduced expression of Na(v)1.6 sodium channels and compensation by Na(v)1.2 channels in mice heterozygous for a null mutation in Scn8a. Neurosci Lett. 2008;442:69-73 pubmed publisher
    ..The reduced amount of Na(v)1.6 protein in Scn8a(+/-) mice is apparently insufficient to saturate the nodal binding sites, allowing Na(v)1.2 channels to compete more successfully. ..
  3. Ogiwara I, Miyamoto H, Morita N, Atapour N, Mazaki E, Inoue I, et al. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci. 2007;27:5903-14 pubmed
    ..Our data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and, furthermore, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. ..
  4. Martin M, Tang B, Ta N, Escayg A. Characterization of 5' untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncoding sequences. Genomics. 2007;90:225-35 pubmed
    The human voltage-gated sodium channel gene cluster on chromosome 2q24 contains three paralogs, SCN1A, SCN2A, and SCN3A, which are expressed in the central nervous system...
  5. Yamagata T, Ogiwara I, Mazaki E, Yanagawa Y, Yamakawa K. Nav1.2 is expressed in caudal ganglionic eminence-derived disinhibitory interneurons: Mutually exclusive distributions of Nav1.1 and Nav1.2. Biochem Biophys Res Commun. 2017;491:1070-1076 pubmed publisher
    ..2 are the voltage-gated sodium channel pore-forming alpha I and II subunits, encoded by the genes SCN1A and SCN2A. Although mutations of both genes have similarly been described in patients with epilepsy, autism and/or ..
  6. Haufe V, Camacho J, Dumaine R, Günther B, Bollensdorff C, von Banchet G, et al. Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. J Physiol. 2005;564:683-96 pubmed
    ..Our data suggest that neuronal and skeletal muscle Na(+) channels contribute to the action potential of cardiomyocytes in the adult mammalian heart. ..
  7. Pilz A, Abbott C. Dinucleotide repeats in the mouse Hox-4.4 and Hox-4.5 genes on chromosome 2, and their analysis in the BXD and BXH recombinant inbred strains. Mamm Genome. 1993;4:129-30 pubmed
  8. Mishra V, Karumuri B, Gautier N, Liu R, Hutson T, Vanhoof Villalba S, et al. Scn2a deletion improves survival and brain-heart dynamics in the Kcna1-null mouse model of sudden unexpected death in epilepsy (SUDEP). Hum Mol Genet. 2017;26:2091-2103 pubmed publisher
    ..Here we evaluated heterozygous Scn2a gene deletion (Scn2a+/-) as a protective genetic modifier in the Kcna1 knockout mouse (Kcna1-/-) model of SUDEP, ..
  9. Hu X, Cheng X, Cai L, Tan G, Xu L, Feng X, et al. Conditional deletion of NRSF in forebrain neurons accelerates epileptogenesis in the kindling model. Cereb Cortex. 2011;21:2158-65 pubmed publisher
    ..Furthermore, the derepression of BDNF was associated by activation of PLC? and PI(3)K signaling pathways. These findings indicate that NRSF functions as an intrinsic repressor of limbic epileptogenesis. ..

More Information


  1. Albrieux M, Platel J, Dupuis A, Villaz M, Moody W. Early expression of sodium channel transcripts and sodium current by cajal-retzius cells in the preplate of the embryonic mouse neocortex. J Neurosci. 2004;24:1719-25 pubmed
    ..These results raise the possibility that populations of pioneer neurons of the PP, including Cajal-Retzius cells, gain neuronal physiological properties early in development via expression of the Na(v)1.3 (SCN3) Na channel isoform. ..
  2. Fotia A, Ekberg J, Adams D, Cook D, Poronnik P, Kumar S. Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2. J Biol Chem. 2004;279:28930-5 pubmed
    ..Interestingly, Nedd4 suppressed the activity of Na(v)1.2 and Na(v)1.7 but was a poor inhibitor of Na(v)1.8. Our results provide evidence that Nedd4 and Nedd4-2 are likely to be key regulators of specific neuronal Na(v) channels in vivo. ..
  3. Kim H, DiBernardo A, Sloane J, Rasband M, Solomon D, Kosaras B, et al. WAVE1 is required for oligodendrocyte morphogenesis and normal CNS myelination. J Neurosci. 2006;26:5849-59 pubmed
    ..Together, these data demonstrate a role for WAVE1 in oligodendrocyte morphogenesis and myelination. ..
  4. Malo D, Schurr E, Dorfman J, Canfield V, Levenson R, Gros P. Three brain sodium channel alpha-subunit genes are clustered on the proximal segment of mouse chromosome 2. Genomics. 1991;10:666-72 pubmed
    ..Physical mapping by pulsed-field gel electrophoresis has established that Scn2a and Scn3a (genes encoding type II and type III sodium channel alpha-subunit isoforms) are physically linked and ..
  5. Perrot R, Lonchampt P, Peterson A, Eyer J. Axonal neurofilaments control multiple fiber properties but do not influence structure or spacing of nodes of Ranvier. J Neurosci. 2007;27:9573-84 pubmed
    ..Thus, many fiber characteristics are controlled through mechanisms operating independently of absolute axon caliber and the neurofilament cytoskeleton. ..
  6. Zha H, Remmers E, Du Y, Goldmuntz E, Mathern P, Zhang H, et al. A single linkage group comprising 11 polymorphic DNA markers on rat chromosome 3. Mamm Genome. 1994;5:538-41 pubmed covering approximately 112 cM with the following order: Ptgs1 (prostaglandin G/H synthase I)-D3Arb178-Scn2a (sodium channel, type II, alpha-polypeptide)-D3Arb1-Cat (catalase)-Bdnf (brain-derived neurotropic factor)-..
  7. Crabbe J, Belknap J, Buck K, Metten P. Use of recombinant inbred strains for studying genetic determinants of responses to alcohol. Alcohol Alcohol Suppl. 1994;2:67-71 pubmed
    ..A cluster of genes (Scn1, Scn2, Scn3) code for voltage-sensitive sodium channel proteins. These genes are plausible candidates for affecting withdrawal HIC. ..
  8. Liao Y, Anttonen A, Liukkonen E, Gaily E, Maljevic S, Schubert S, et al. SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain. Neurology. 2010;75:1454-8 pubmed publisher
    Inherited and de novo mutations in sodium channel genes underlie a variety of channelopathies. Mutations in SCN2A, encoding the brain sodium channel Na(V)1...
  9. Gao N, Lu M, Echeverri F, Laita B, Kalabat D, Williams M, et al. Voltage-gated sodium channels in taste bud cells. BMC Neurosci. 2009;10:20 pubmed publisher
    ..The molecular identity of the voltage-gated sodium channels that sense depolarizing signals and subsequently initiate action potentials coding taste information to gustatory nerve fibers is unknown...
  10. Beckers M, Ernst E, Belcher S, Howe J, Levenson R, Gros P. A new sodium channel alpha-subunit gene (Scn9a) from Schwann cells maps to the Scn1a, Scn2a, Scn3a cluster of mouse chromosome 2. Genomics. 1996;36:202-5 pubmed
  11. Ballas N, Grunseich C, Lu D, Speh J, Mandel G. REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell. 2005;121:645-657 pubmed publisher
    ..Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli. ..
  12. Bergren S, Chen S, Galecki A, Kearney J. Genetic modifiers affecting severity of epilepsy caused by mutation of sodium channel Scn2a. Mamm Genome. 2005;16:683-90 pubmed
    ..Modifier genes affecting clinical severity in the Scn 2 a(Q 54) mouse model may contribute to the variable expressivity seen in epilepsy patients with sodium channel mutations. ..
  13. Notwell J, Heavner W, Darbandi S, Katzman S, McKenna W, Ortiz Londono C, et al. TBR1 regulates autism risk genes in the developing neocortex. Genome Res. 2016;26:1013-22 pubmed publisher
    ..Our findings highlight a TBR1-regulated network of ASD genes in the developing neocortex that are relatively intolerant to LoF mutations, indicating that these genes may play critical roles in normal cortical development. ..
  14. Figueroa X, Chen C, Campbell K, Damon D, Day K, Ramos S, et al. Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone?. Am J Physiol Heart Circ Physiol. 2007;293:H1371-83 pubmed
    ..2 channels. The resultant Ca(2+) influx activates endothelial nitric oxide synthase and Ca(2+)-activated K(+) channels, triggering vasodilation. ..
  15. Litt M, Luty J, Kwak M, Allen L, Magenis R, Mandel G. Localization of a human brain sodium channel gene (SCN2A) to chromosome 2. Genomics. 1989;5:204-8 pubmed
    ..used to localize on human chromosomes a gene coding for the alpha-subunit of the brain type II sodium channel (SCN2A)...
  16. Stevens M, Timmermans S, Bottelbergs A, Hendriks J, Brône B, Baes M, et al. Block of a subset of sodium channels exacerbates experimental autoimmune encephalomyelitis. J Neuroimmunol. 2013;261:21-8 pubmed publisher
    ..2 and Nav1.6 expression levels were elevated in brain but not in spinal cord of Midi-treated mice, implicating that Navs play a complex role in the pathogenesis of EAE. ..
  17. Planells Cases R, Caprini M, Zhang J, Rockenstein E, Rivera R, Murre C, et al. Neuronal death and perinatal lethality in voltage-gated sodium channel alpha(II)-deficient mice. Biophys J. 2000;78:2878-91 pubmed
    ..Death appears to arise from severe hypoxia consequent to the brainstem deficiency of NaChalpha(II). NaChalpha(II) expression is, therefore, redundant for embryonic development but essential for postnatal survival. ..
  18. Hossain W, Antic S, Yang Y, Rasband M, Morest D. Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea. J Neurosci. 2005;25:6857-68 pubmed
  19. Martínez Hernández J, Ballesteros Merino C, Fernandez Alacid L, Nicolau J, Aguado C, Lujan R. Polarised localisation of the voltage-gated sodium channel Na(v)1.2 in cerebellar granule cells. Cerebellum. 2013;12:16-26 pubmed publisher
    ..The present findings show a polarised distribution of Na(v)1.2 along the neuronal surface of granule cells and suggest its primary involvement in the transmission of information from granule cells to Purkinje cells. ..
  20. Nakamura T, Yabe D, Kanazawa N, Tashiro K, Sasayama S, Honjo T. Molecular cloning, characterization, and chromosomal localization of FKBP23, a novel FK506-binding protein with Ca2+-binding ability. Genomics. 1998;54:89-98 pubmed
    ..FKBP23 mRNA is expressed most strongly in heart, lung, and testis, beginning at day 8.5 of embryonic development. The FKBP23 gene was mapped to mouse chromosome 2. ..
  21. Gazina E, Leaw B, Richards K, Wimmer V, Kim T, Aumann T, et al. 'Neonatal' Nav1.2 reduces neuronal excitability and affects seizure susceptibility and behaviour. Hum Mol Genet. 2015;24:1457-68 pubmed publisher
    ..However, inhibitory postsynaptic currents in NaV1.2(adult) neurons were larger and the expression level of Scn2a mRNA was 24% lower compared with the WT. The enhanced seizure susceptibility of the NaV1...
  22. Li T, Tian C, Scalmani P, Frassoni C, Mantegazza M, Wang Y, et al. Action potential initiation in neocortical inhibitory interneurons. PLoS Biol. 2014;12:e1001944 pubmed publisher
    ..Together, our results reveal the molecular identity of axonal Na+ channels in interneurons and their contribution to AP generation and regulation of network activity. ..
  23. Hawkins N, Martin M, Frankel W, Kearney J, Escayg A. Neuronal voltage-gated ion channels are genetic modifiers of generalized epilepsy with febrile seizures plus. Neurobiol Dis. 2011;41:655-60 pubmed publisher
    Mutations in the neuronal voltage-gated sodium channel genes SCN1A and SCN2A are associated with inherited epilepsies, including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (severe myoclonic epilepsy of ..
  24. Vega A, Avila G, Matthews G. Interaction between the transcriptional corepressor Sin3B and voltage-gated sodium channels modulates functional channel expression. Sci Rep. 2013;3:2809 pubmed publisher
  25. Rush A, Dib Hajj S, Waxman S. Electrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in mouse spinal sensory neurones. J Physiol. 2005;564:803-15 pubmed
    ..6 and the Na(+)/Ca(2+) exchanger are colocalized, while selective expression of Na(v)1.2 may support action potential electrogenesis, at least at lower frequencies, while producing a smaller persistent current. ..
  26. Thomas E, Hawkins R, Richards K, Xu R, Gazina E, Petrou S. Heat opens axon initial segment sodium channels: a febrile seizure mechanism?. Ann Neurol. 2009;66:219-26 pubmed publisher
    ..The direct effect of heat on ion channels localized to the site of action potential initiation potentially causes a profound increase in neuronal excitability. This is likely to contribute to febrile seizure genesis. ..
  27. Zhang M, Green B, Catlin P, Fiedler B, Azam L, Chadwick A, et al. Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels. J Biol Chem. 2007;282:30699-706 pubmed
    ..2 and that further engineering of micro-conopeptides belonging to the KIIIA group may provide subtype-selective pharmacological compounds for mammalian neuronal sodium channels and potential therapeutics for the treatment of pain. ..
  28. Tsunozaki M, Lennertz R, Vilceanu D, Katta S, Stucky C, Bautista D. A 'toothache tree' alkylamide inhibits A? mechanonociceptors to alleviate mechanical pain. J Physiol. 2013;591:3325-40 pubmed publisher
    ..These results suggest that sanshool targets voltage-gated sodium channels on A? mechanosensory nociceptors to dampen excitability and thus induce 'fast pain' analgesia. ..
  29. Sashihara S, Yanagihara N, Kobayashi H, Izumi F, Tsuji S, Murai Y, et al. Overproduction of voltage-dependent Na+ channels in the developing brain of genetically seizure-susceptible E1 mice. Neuroscience. 1992;48:285-91 pubmed
    ..05 +/- 0.03 nM; E1, 1.03 +/- 0.01 nM). Lastly, veratridine-evoked 22Na+ influx, sensitive to tetrodotoxin, was increased approximately 45% in the cortical synaptosomes in six-week-old E1 mice.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  30. Kile K, Tian N, Durand D. Scn2a sodium channel mutation results in hyperexcitability in the hippocampus in vitro. Epilepsia. 2008;49:488-99 pubmed
    ..of the hippocampus in Q54 mice that display spontaneous seizures because of a gain-of-function mutation of the Scn2a sodium channel gene...