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    SCN2A sodium voltage-gated channel alpha subunit 2 [ Homo sapiens (human) ]

    Gene ID: 6326, updated on 10-Dec-2024

    Summary

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    Official Symbol
    SCN2Aprovided by HGNC
    Official Full Name
    sodium voltage-gated channel alpha subunit 2provided by HGNC
    Primary source
    HGNC:HGNC:10588
    See related
    Ensembl:ENSG00000136531 MIM:182390; AllianceGenome:HGNC:10588
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    EA9; HBA; NAC2; BFIC3; BFIS3; BFNIS; DEE11; HBSCI; EIEE11; HBSCII; Nav1.2; SCN2A1; SCN2A2; Na(v)1.2
    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. [provided by RefSeq, Nov 2016]
    Expression
    Biased expression in brain (RPKM 20.5) and kidney (RPKM 1.1) See more
    Orthologs
    mouse all
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    Genomic context

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    See SCN2A in Genome Data Viewer
    Location:
    2q24.3
    Exon count:
    31
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (165239414..165392304)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (165696714..165849575)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (166095924..166248814)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene NANOG hESC enhancer GRCh37_chr2:165769454-165769970 Neighboring gene RNA, 5S ribosomal pseudogene 111 Neighboring gene solute carrier family 38 member 11 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:165840567-165840754 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:165851409-165851909 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:165926349-165926850 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:165926851-165927350 Neighboring gene sodium voltage-gated channel alpha subunit 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12066 Neighboring gene Sharpr-MPRA regulatory region 13511 Neighboring gene MAPRE1 pseudogene 3 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:166279515-166280129 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:166283004-166283939 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:166317128-166318327 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:166385525-166386157 Neighboring gene cysteine and serine rich nuclear protein 3 Neighboring gene MPRA-validated peak3912 silencer Neighboring gene NANOG hESC enhancer GRCh37_chr2:166436961-166437478 Neighboring gene NANOG hESC enhancer GRCh37_chr2:166437479-166437996 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16726 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16727 Neighboring gene uncharacterized LOC124906085 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:166490986-166491565 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:166491566-166492144 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:166564017-166564558 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:166565101-166565640 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:166593391-166593948 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:166649507-166650413 Neighboring gene uncharacterized LOC124906086 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:166650414-166651319 Neighboring gene polypeptide N-acetylgalactosaminyltransferase 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Confirming an expanded spectrum of SCN2A mutations: a case series. Matalon D, et al. Epileptic Disord, 2014 Mar. PMID 24659627
    2. Clinical spectrum of SCN2A mutations. Shi X, et al. Brain Dev, 2012 Aug. PMID 22029951
    3. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Sanders SJ, et al. Nature, 2012 Apr 4. PMID 22495306, Free PMC Article
    4. Different degrees of loss of function between GEFS+ and SMEI Nav 1.1 missense mutants at the same residue induced by rescuable folding defects. Sugiura Y, et al. Epilepsia, 2012 Jun. PMID 22525008
    5. Acute encephalopathy with a novel point mutation in the SCN2A gene. Kobayashi K, et al. Epilepsy Res, 2012 Nov. PMID 22591750

    See all (150) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Pathogenic gating pore current conducted by autism-related mutations in the NaV1.2 brain sodium channel.
      Title: Pathogenic gating pore current conducted by autism-related mutations in the Na(V)1.2 brain sodium channel.
    2. Distinctive In Vitro Phenotypes in iPSC-Derived Neurons From Patients With Gain- and Loss-of-Function SCN2A Developmental and Epileptic Encephalopathy.
      Title: Distinctive In Vitro Phenotypes in iPSC-Derived Neurons From Patients With Gain- and Loss-of-Function SCN2A Developmental and Epileptic Encephalopathy.
    3. Exome sequencing of ATP1A3-negative cases of alternating hemiplegia of childhood reveals SCN2A as a novel causative gene.
      Title: Exome sequencing of ATP1A3-negative cases of alternating hemiplegia of childhood reveals SCN2A as a novel causative gene.
    4. Epilepsy-associated SCN2A (NaV1.2) variants exhibit diverse and complex functional properties.
      Title: Epilepsy-associated SCN2A (NaV1.2) variants exhibit diverse and complex functional properties.
    5. Missense mutations in the membrane domain of PRRT2 affect its interaction with Nav1.2 voltage-gated sodium channels.
      Title: Missense mutations in the membrane domain of PRRT2 affect its interaction with Nav1.2 voltage-gated sodium channels.
    6. Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons.
      Title: Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons.
    7. A Push-Pull Mechanism Between PRRT2 and beta4-subunit Differentially Regulates Membrane Exposure and Biophysical Properties of NaV1.2 Sodium Channels.
      Title: A Push-Pull Mechanism Between PRRT2 and β4-subunit Differentially Regulates Membrane Exposure and Biophysical Properties of NaV1.2 Sodium Channels.
    8. Association of sodium voltage-gated channel genes polymorphisms with epilepsy risk and prognosis in the Saudi population.
      Title: Association of sodium voltage-gated channel genes polymorphisms with epilepsy risk and prognosis in the Saudi population.
    9. Functional correlates of clinical phenotype and severity in recurrent SCN2A variants.
      Title: Functional correlates of clinical phenotype and severity in recurrent SCN2A variants.
    10. Role of SCN2A c.56G/A Gene Polymorphism in Egyptian Children with Genetic Epilepsy with Febrile Seizure Plus.
      Title: Role of SCN2A c.56G/A Gene Polymorphism in Egyptian Children with Genetic Epilepsy with Febrile Seizure Plus.
    Submit: New GeneRIF Correction See all GeneRIFs (111)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Developmental and epileptic encephalopathy, 11
    MedGen: C3150987 OMIM: 613721 GeneReviews: Not available
    		Compare labs
    Episodic ataxia, type 9
    MedGen: C5394520 OMIM: 618924 GeneReviews: Not available
    		Compare labs
    SCN2A-related generalized epilepsy with febrile seizures plus
    MedGen: CN120574 GeneReviews: Not available
    		Compare labs
    Seizures, benign familial infantile, 3
    MedGen: C1843140 OMIM: 607745 GeneReviews: Not available
    		Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-04-22)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-04-22)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    Common variants associated with general and MMR vaccine-related febrile seizures.
    EBI GWAS Catalog
    Genome-wide association study of chronic periodontitis in a general German population.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calmodulin binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables voltage-gated sodium channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables voltage-gated sodium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables voltage-gated sodium channel activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables voltage-gated sodium channel activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in cardiac muscle cell action potential involved in contraction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to hypoxia ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in dentate gyrus development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in determination of adult lifespan IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within intrinsic apoptotic signaling pathway in response to osmotic stress ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in memory ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in myelination ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in nerve development IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within nervous system development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    acts_upstream_of_or_within neuron apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in neuronal action potential IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in neuronal action potential ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in sodium ion transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within sodium ion transport ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in T-tubule IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in axon TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in intercalated disc IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in node of Ranvier ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in paranode region of axon IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in presynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of voltage-gated sodium channel complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of voltage-gated sodium channel complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    sodium channel protein type 2 subunit alpha
    Names
    sodium channel protein brain II subunit alpha
    sodium channel protein type II subunit alpha
    sodium channel protein, brain type 2 alpha subunit
    sodium channel, voltage-gated, type II, alpha 1 polypeptide
    sodium channel, voltage-gated, type II, alpha 2 polypeptide
    sodium channel, voltage-gated, type II, alpha subunit
    voltage-gated sodium channel subtype II
    voltage-gated sodium channel subunit alpha Nav1.2
    voltage-gated sodium channel type II alpha subunit

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008143.1 RefSeqGene

      Range
      5013..157903
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001040142.2 → NP_001035232.1  sodium channel protein type 2 subunit alpha isoform 1

      See identical proteins and their annotated locations for NP_001035232.1

      Status: REVIEWED

      Source sequence(s)
      AC011303, BP199510, BP311214, BU729783, DA232976, M94055
      Consensus CDS
      CCDS33314.1
      UniProtKB/Swiss-Prot
      A6NC14, A6NIQ5, Q14472, Q53T77, Q99250, Q9BZC9, Q9BZD0
      UniProtKB/TrEMBL
      A0A1B0GWA6
      Related
      ENSP00000364586.2, ENST00000375437.7
      Conserved Domains (5) summary
      cd13433
      Location:1474 → 1526
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1207 → 1482
      Ion_trans; Ion transport protein
      pfam06512
      Location:997 → 1203
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:514 → 709
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel
      pfam16905
      Location:1798 → 1845
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated

    2. NM_001040143.2 → NP_001035233.1  sodium channel protein type 2 subunit alpha isoform 2

      See identical proteins and their annotated locations for NP_001035233.1

      Status: REVIEWED

      Source sequence(s)
      AC011303, AC013438
      Consensus CDS
      CCDS33313.1
      UniProtKB/TrEMBL
      A0A1B0GWA6
      Related
      ENSP00000490107.1, ENST00000636071.2
      Conserved Domains (5) summary
      cd13433
      Location:1474 → 1526
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1207 → 1482
      Ion_trans; Ion transport protein
      pfam06512
      Location:997 → 1203
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:514 → 709
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel
      pfam16905
      Location:1798 → 1845
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated

    3. NM_001371246.1 → NP_001358175.1  sodium channel protein type 2 subunit alpha isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC011303, AC013438
      Consensus CDS
      CCDS33313.1
      UniProtKB/TrEMBL
      A0A1B0GWA6
      Related
      ENSP00000486885.1, ENST00000631182.3
      Conserved Domains (5) summary
      cd13433
      Location:1474 → 1526
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1207 → 1482
      Ion_trans; Ion transport protein
      pfam06512
      Location:997 → 1203
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:514 → 709
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel
      pfam16905
      Location:1798 → 1845
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated

    4. NM_001371247.1 → NP_001358176.1  sodium channel protein type 2 subunit alpha isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC011303, AC013438
      Consensus CDS
      CCDS33314.1
      UniProtKB/Swiss-Prot
      A6NC14, A6NIQ5, Q14472, Q53T77, Q99250, Q9BZC9, Q9BZD0
      UniProtKB/TrEMBL
      A0A1B0GWA6
      Related
      ENSP00000490866.1, ENST00000637266.2
      Conserved Domains (5) summary
      cd13433
      Location:1474 → 1526
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1207 → 1482
      Ion_trans; Ion transport protein
      pfam06512
      Location:997 → 1203
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:514 → 709
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel
      pfam16905
      Location:1798 → 1845
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated

    5. NM_021007.3 → NP_066287.2  sodium channel protein type 2 subunit alpha isoform 1

      See identical proteins and their annotated locations for NP_066287.2

      Status: REVIEWED

      Source sequence(s)
      AC011303
      Consensus CDS
      CCDS33314.1
      UniProtKB/Swiss-Prot
      A6NC14, A6NIQ5, Q14472, Q53T77, Q99250, Q9BZC9, Q9BZD0
      UniProtKB/TrEMBL
      A0A1B0GWA6
      Related
      ENSP00000283256.6, ENST00000283256.10
      Conserved Domains (5) summary
      cd13433
      Location:1474 → 1526
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1207 → 1482
      Ion_trans; Ion transport protein
      pfam06512
      Location:997 → 1203
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:514 → 709
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel
      pfam16905
      Location:1798 → 1845
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      165239414..165392304
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      165696714..165849575
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q99250.3 GenPept UniProtKB/Swiss-Prot:Q99250

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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