Gene: SCN2A

Alternate names for this Gene: BFIC3|BFIS3|BFNIS|DEE11|EA9|EIEE11|HBA|HBSCI|HBSCII|NAC2|Na(v)1.2|Nav1.2|SCN2A1|SCN2A2

Gene Summary: Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. Voltage-gated sodium channels function in the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. Allelic variants of this gene are associated with seizure disorders and autism spectrum disorder. Alternative splicing results in multiple transcript variants.

Gene is located in Chromosome: 2

Location in Chromosome : 2q24.3

Description of this Gene: sodium voltage-gated channel alpha subunit 2

Type of Gene: protein-coding

rs2060199 in SCN2A gene and Age at menarche PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs17183814 in SCN2A gene and Bipolar Disorder PMID 31043756 2019 Genome-wide association study identifies 30 loci associated with bipolar disorder.

rs12477385 in SCN2A gene and Body mass index PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 30239722 2019 Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.

rs1553583712 in SCN2A gene and Dysmorphic features PMID 23033978 2012 Diagnostic exome sequencing in persons with severe intellectual disability.

PMID 23020937 2012 Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.

PMID 22495306 2012 De novo mutations revealed by whole-exome sequencing are strongly associated with autism.

PMID 26645390 2016 Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia.

PMID 24267886 2013 Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism.

PMID 23827426 2013 SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism.

PMID 23935176 2013 Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome.

PMID 20346423 2010 Array-CGH detection of a de novo 2.8 Mb deletion in 2q24.2-->q24.3 in a girl with autistic features and developmental delay.

PMID 23849776 2013 Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.

PMID 26993267 2016 Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis.

PMID 15249644 2004 Severe epilepsy, retardation, and dysmorphic features with a 2q deletion including SCN1A and SCN2A.

PMID 28256214 2017 Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures.

PMID 1658783 1991 Brain and heart sodium channel subtype mRNA expression in rat cerebral cortex.

PMID 20196795 2010 Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009.

PMID 18809926 2008 Disulfide locking a sodium channel voltage sensor reveals ion pair formation during activation.

PMID 22581936 2012 Clinical application of exome sequencing in undiagnosed genetic conditions.

PMID 22029951 2012 Clinical spectrum of SCN2A mutations.

PMID 20351042 2010 Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects.

PMID 20006674 2010 Differential expression of exon 5 splice variants of sodium channel alpha subunit mRNAs in the developing mouse brain.

PMID 28379373 2017 Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders.

PMID 26291284 2015 SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures.

PMID 23708187 2013 Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

PMID 19786696 2009 De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies.

PMID 18479388 2008 Impaired NaV1.2 function and reduced cell surface expression in benign familial neonatal-infantile seizures.

PMID 17467289 2007 A childhood epilepsy mutation reveals a role for developmentally regulated splicing of a sodium channel.

PMID 1325650 1992 Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain.

PMID 15048894 2004 Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy.

PMID 17386050 2007 SCN2A mutations and benign familial neonatal-infantile seizures: the phenotypic spectrum.

PMID 15101391 2004 Evolutionary convergence of alternative splicing in ion channels.

PMID 11245985 2001 Genomic structures of SCN2A and SCN3A - candidate genes for deafness at the DFNA16 locus.

PMID 25163687 2014 Genotype phenotype associations across the voltage-gated sodium channel family.

PMID 24579881 2014 Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscular hypotonia, and brain abnormalities.

PMID 1658739 1991 Developmentally regulated alternative RNA splicing of rat brain sodium channel mRNAs.

PMID 10198179 1999 Evolution and diversity of mammalian sodium channel genes.

rs121917751 in SCN2A gene and EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 11 PMID 29215089 2018 Genetic analysis of benign familial epilepsies in the first year of life in a Chinese cohort.

PMID 15048894 2004 Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy.

PMID 23360469 2013 Genetic testing in benign familial epilepsies of the first year of life: clinical and diagnostic significance.

PMID 19783390 2009 Missense mutation of the sodium channel gene SCN2A causes Dravet syndrome.

PMID 23033978 2012 Diagnostic exome sequencing in persons with severe intellectual disability.

PMID 23662938 2013 Targeted capture and sequencing for detection of mutations causing early onset epileptic encephalopathy.

PMID 25457084 2015 A case of recurrent encephalopathy with SCN2A missense mutation.

PMID 23988467 2013 Novel de novo SCN2A mutation in a child with migrating focal seizures of infancy.

PMID 23550958 2013 Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings.

PMID 24710820 2014 Infantile epileptic encephalopathy, transient choreoathetotic movements, and hypersomnia due to a De Novo missense mutation in the SCN2A gene.

PMID 20956790 2010 SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain.

PMID 24463883 2014 Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis.

PMID 22677033 2012 Compromised function in the Na(v)1.2 Dravet syndrome mutation R1312T.

PMID 25459969 2015 SCN2A mutation in a Chinese boy with infantile spasm - response to Modified Atkins Diet.

PMID 24659627 2014 Confirming an expanded spectrum of SCN2A mutations: a case series.

PMID 23708187 2013 Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

PMID 30144217 2018 Relationship of electrophysiological dysfunction and clinical severity in SCN2A-related epilepsies.

PMID 25818041 2015 Diagnostic yield of genetic testing in epileptic encephalopathy in childhood.

PMID 26993267 2016 Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis.

PMID 23935176 2013 Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome.

PMID 30415926 2019 Ketogenic diet as a successful early treatment modality for SCN2A mutation.

PMID 25772804 2015 De novo R853Q mutation of SCN2A gene and West syndrome.

PMID 26291284 2015 SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures.

PMID 28379373 2017 Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders.

PMID 27824329 2016 De novo genic mutations among a Chinese autism spectrum disorder cohort.

PMID 27781031 2016 Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies.

PMID 19786696 2009 De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies.

PMID 29186148 2017 A case-control collapsing analysis identifies epilepsy genes implicated in trio sequencing studies focused on de novo mutations.

PMID 26648591 2016 Unexplained early onset epileptic encephalopathy: Exome screening and phenotype expansion.

PMID 27867041 2017 Infantile Epileptic Encephalopathy Associated With SCN2A Mutation Responsive to Oral Mexiletine.

PMID 28554332 2017 Genomic diagnosis for children with intellectual disability and/or developmental delay.

rs796053124 in SCN2A gene and Epilepsy PMID 20956790 2010 SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain.

rs1553574522 in SCN2A gene and Epilepsy, Rolandic PMID 29358611 2018 Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy.

rs796053124 in SCN2A gene and Episodic Ataxia PMID 20956790 2010 SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain.

rs12477385 in SCN2A gene and Factor VII measurement PMID 30642921 2019 A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology.

rs3769955 in SCN2A gene and Febrile Convulsions PMID 25344690 2014 Furthermore, four loci were associated with febrile seizures in general, implicating the sodium channel genes SCN1A (rs6432860: P = 2.2 × 10(-16)) and SCN2A (rs3769955: P = 3.1 × 10(-10)), a TMEM16 family gene (ANO3; rs114444506: P = 3.7 × 10(-20)) and a region associated with magnesium levels (12q21.33; rs11105468: P = 3.4 × 10(-11)).

rs1446577 in SCN2A gene and Intelligence PMID 29844566 2018 Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.

rs1553583712 in SCN2A gene and Muscle hypotonia PMID 1325650 1992 Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain.

PMID 20351042 2010 Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects.

PMID 17386050 2007 SCN2A mutations and benign familial neonatal-infantile seizures: the phenotypic spectrum.

PMID 22495306 2012 De novo mutations revealed by whole-exome sequencing are strongly associated with autism.

PMID 1658783 1991 Brain and heart sodium channel subtype mRNA expression in rat cerebral cortex.

PMID 18809926 2008 Disulfide locking a sodium channel voltage sensor reveals ion pair formation during activation.

PMID 23849776 2013 Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.

PMID 18479388 2008 Impaired NaV1.2 function and reduced cell surface expression in benign familial neonatal-infantile seizures.

PMID 26645390 2016 Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia.

PMID 26993267 2016 Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis.

PMID 28379373 2017 Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders.

PMID 28256214 2017 Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures.

PMID 20346423 2010 Array-CGH detection of a de novo 2.8 Mb deletion in 2q24.2-->q24.3 in a girl with autistic features and developmental delay.

PMID 23827426 2013 SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism.

PMID 24267886 2013 Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism.

PMID 26291284 2015 SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures.

PMID 15249644 2004 Severe epilepsy, retardation, and dysmorphic features with a 2q deletion including SCN1A and SCN2A.

PMID 20006674 2010 Differential expression of exon 5 splice variants of sodium channel alpha subunit mRNAs in the developing mouse brain.

PMID 23708187 2013 Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

PMID 22029951 2012 Clinical spectrum of SCN2A mutations.

PMID 23935176 2013 Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome.

PMID 25163687 2014 Genotype phenotype associations across the voltage-gated sodium channel family.

PMID 24579881 2014 Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscular hypotonia, and brain abnormalities.

PMID 23033978 2012 Diagnostic exome sequencing in persons with severe intellectual disability.

PMID 15101391 2004 Evolutionary convergence of alternative splicing in ion channels.

PMID 17467289 2007 A childhood epilepsy mutation reveals a role for developmentally regulated splicing of a sodium channel.

PMID 22581936 2012 Clinical application of exome sequencing in undiagnosed genetic conditions.

PMID 19786696 2009 De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies.

PMID 23020937 2012 Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.

PMID 11245985 2001 Genomic structures of SCN2A and SCN3A - candidate genes for deafness at the DFNA16 locus.

PMID 15048894 2004 Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy.

PMID 20196795 2010 Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009.

PMID 1658739 1991 Developmentally regulated alternative RNA splicing of rat brain sodium channel mRNAs.

PMID 10198179 1999 Evolution and diversity of mammalian sodium channel genes.

rs353116 in SCN2A gene and Parkinson Disease PMID 28892059 2017 A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.

rs121917748 in SCN2A gene and SEIZURES, BENIGN FAMILIAL INFANTILE, 3 PMID 29844171 2018 Dynamic action potential clamp predicts functional separation in mild familial and severe de novo forms of SCN2A epilepsy.

PMID 20371507 2010 Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy.

PMID 30144217 2018 Relationship of electrophysiological dysfunction and clinical severity in SCN2A-related epilepsies.

PMID 26291284 2015 SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures.

PMID 23360469 2013 Genetic testing in benign familial epilepsies of the first year of life: clinical and diagnostic significance.

PMID 25982755 2015 Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome.

PMID 22612257 2012 Targeted next generation sequencing as a diagnostic tool in epileptic disorders.

PMID 20298421 2010 EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias.

PMID 18479388 2008 Impaired NaV1.2 function and reduced cell surface expression in benign familial neonatal-infantile seizures.

PMID 15048894 2004 Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy.

PMID 23758435 2013 An SCN2A mutation in a family with infantile seizures from Madagascar reveals an increased subthreshold Na(+) current.

PMID 17021166 2006 Effects in neocortical neurons of mutations of the Na(v)1.2 Na+ channel causing benign familial neonatal-infantile seizures.

PMID 16417554 2006 A novel SCN2A mutation in family with benign familial infantile seizures.

PMID 12243921 2002 Sodium-channel defects in benign familial neonatal-infantile seizures.

PMID 11371648 2001 A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction.

PMID 17386050 2007 SCN2A mutations and benign familial neonatal-infantile seizures: the phenotypic spectrum.

PMID 18479388 2008 We examined three BFNIS mutations (R1319Q, L1330F, and L1563V) using whole-cell patch-clamp recording of heterologously expressed human Na(V)1.2.

PMID 18479388 2008 We examined three BFNIS mutations (R1319Q, L1330F, and L1563V) using whole-cell patch-clamp recording of heterologously expressed human Na(V)1.2.

PMID 29215089 2018 Genetic analysis of benign familial epilepsies in the first year of life in a Chinese cohort.

PMID 18479388 2008 We examined three BFNIS mutations (R1319Q, L1330F, and L1563V) using whole-cell patch-clamp recording of heterologously expressed human Na(V)1.2.

PMID 28379373 2017 Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders.

PMID 27824329 2016 De novo genic mutations among a Chinese autism spectrum disorder cohort.

PMID 27781031 2016 Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies.

PMID 19786696 2009 De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies.

PMID 23935176 2013 Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome.

PMID 29186148 2017 A case-control collapsing analysis identifies epilepsy genes implicated in trio sequencing studies focused on de novo mutations.

PMID 25772804 2015 De novo R853Q mutation of SCN2A gene and West syndrome.

PMID 27867041 2017 Infantile Epileptic Encephalopathy Associated With SCN2A Mutation Responsive to Oral Mexiletine.

PMID 26993267 2016 Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis.

PMID 26648591 2016 Unexplained early onset epileptic encephalopathy: Exome screening and phenotype expansion.

PMID 28554332 2017 Genomic diagnosis for children with intellectual disability and/or developmental delay.

rs796053124 in SCN2A gene and Vertigo PMID 20956790 2010 SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain.

rs12469667 in SCN2A gene and Waist-Hip Ratio PMID 30239722 2019 Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.

rs7581427 in SCN2A gene and mathematical ability PMID 30038396 2018 Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.