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    SCN4A sodium voltage-gated channel alpha subunit 4 [ Homo sapiens (human) ]

    Gene ID: 6329, updated on 20-Apr-2024

    Summary

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    Official Symbol
    SCN4Aprovided by HGNC
    Official Full Name
    sodium voltage-gated channel alpha subunit 4provided by HGNC
    Primary source
    HGNC:HGNC:10591
    See related
    Ensembl:ENSG00000007314 MIM:603967; AllianceGenome:HGNC:10591
    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
    HYPP; SkM1; CMS16; HYKPP; NAC1A; HOKPP2; Nav1.4; CMYP22A; Na(V)1.4
    Summary
    Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. It is expressed in skeletal muscle, and mutations in this gene have been linked to several myotonia and periodic paralysis disorders. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in fat (RPKM 9.2), thyroid (RPKM 1.5) and 3 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    17q23.3
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (63938554..63972918, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (64809317..64843693, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (62015914..62050278, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC112268204 Neighboring gene IGHD type 1A-2 recombination region Neighboring gene growth hormone locus control region Neighboring gene growth hormone 1 Neighboring gene CD79b molecule Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:62036321-62037320 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:62037321-62038319 Neighboring gene uncharacterized LOC105371858 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:62044651-62044849 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:62045661-62046161 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:62064225-62064778 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:62064779-62065330 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8836 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:62075897-62076874 Neighboring gene PRR29 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:62083286-62083980 Neighboring gene proline rich 29 Neighboring gene intercellular adhesion molecule 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12571 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:62097827-62098327

    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. Hyperkalemic periodic paralysis associated with a novel missense variant located in the inner pore of Nav1.4. Segawa K, et al. Brain Dev, 2023 Apr. PMID 36628799
    2. Periodic paralysis due to cumulative effects of rare variants in SCN4A with small functional alterations. Shibano M, et al. Muscle Nerve, 2022 Dec. PMID 36116128
    3. Clinical comparison and functional study of the L703P: a recurrent mutation in human SCN4A that causes sodium channel myotonia. Ke Q, et al. Neuromuscul Disord, 2022 Oct. PMID 36050252
    4. Differences in local anaesthetic and antiepileptic binding in the inactivated state of human sodium channel Nav1.4. Buyan A, et al. Biophys J, 2021 Dec 21. PMID 34774501, Free PMC Article
    5. p.Asn1180Ile mutation of SCN4A gene in an Italian family with myopathy and myotonic syndrome. Rigamonti A, et al. Neurol Sci, 2021 Dec. PMID 34378097

    See all (158) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. [Prenatal diagnosis of a case with Congenital myasthenic syndrome due to compound heterozygous variants of SCN4A gene].
      Title: [Prenatal diagnosis of a case with Congenital myasthenic syndrome due to compound heterozygous variants of SCN4A gene].
    2. [Two cases of potassium-aggravated myotonia induced by SCN4A gene variation].
      Title: [Two cases of potassium-aggravated myotonia induced by SCN4A gene variation].
    3. Hyperkalemic periodic paralysis associated with a novel missense variant located in the inner pore of Nav1.4.
      Title: Hyperkalemic periodic paralysis associated with a novel missense variant located in the inner pore of Nav1.4.
    4. Coexistence of SCN4A and CLCN1 mutations in a family with atypical myotonic features: A clinical and functional study.
      Title: Coexistence of SCN4A and CLCN1 mutations in a family with atypical myotonic features: A clinical and functional study.
    5. Periodic paralysis due to cumulative effects of rare variants in SCN4A with small functional alterations.
      Title: Periodic paralysis due to cumulative effects of rare variants in SCN4A with small functional alterations.
    6. Clinical comparison and functional study of the L703P: a recurrent mutation in human SCN4A that causes sodium channel myotonia.
      Title: Clinical comparison and functional study of the L703P: a recurrent mutation in human SCN4A that causes sodium channel myotonia.
    7. Sequence CLCN1 and SCN4A genes in patients with nondystrophic myotonia in Chinese people.
      Title: Sequence CLCN1 and SCN4A genes in patients with nondystrophic myotonia in Chinese people.
    8. Differences in local anaesthetic and antiepileptic binding in the inactivated state of human sodium channel Nav1.4.
      Title: Differences in local anaesthetic and antiepileptic binding in the inactivated state of human sodium channel Nav1.4.
    9. Mutations associated with hypokalemic periodic paralysis: from hotspot regions to complete analysis of CACNA1S and SCN4A genes.
      Title: Mutations associated with hypokalemic periodic paralysis: from hotspot regions to complete analysis of CACNA1S and SCN4A genes.
    10. Clinical and genetic spectrum of a Chinese cohort with SCN4A gene mutations.
      Title: Clinical and genetic spectrum of a Chinese cohort with SCN4A gene mutations.
    Submit: New GeneRIF Correction See all GeneRIFs (117)

    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
    Congenital myasthenic syndrome 16
    MedGen: C3280112 OMIM: 614198 GeneReviews: Congenital Myasthenic Syndromes Overview
    		Compare labs
    Congenital myopathy 22A, classic
    MedGen: C5830453 OMIM: 620351 GeneReviews: Not available
    		not available
    Congenital myopathy 22B, severe fetal
    MedGen: C5830501 OMIM: 620369 GeneReviews: Not available
    		not available
    Hyperkalemic periodic paralysis
    MedGen: C0238357 OMIM: 170500 GeneReviews: Hyperkalemic Periodic Paralysis
    		Compare labs
    Hypokalemic periodic paralysis, type 1
    MedGen: C3714580 OMIM: 170400 GeneReviews: Hypokalemic Periodic Paralysis
    		Compare labs
    Hypokalemic periodic paralysis, type 2
    MedGen: C2750061 OMIM: 613345 GeneReviews: Hypokalemic Periodic Paralysis
    		Compare labs
    Paramyotonia congenita of Von Eulenburg
    MedGen: C0221055 OMIM: 168300 GeneReviews: Not available
    		Compare labs
    Potassium-aggravated myotonia
    MedGen: C2931826 OMIM: 608390 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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 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 
    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 muscle contraction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of skeletal muscle contraction by action potential IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in sodium ion transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sodium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sodium ion transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of voltage-gated sodium channel complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of voltage-gated sodium channel complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    sodium channel protein type 4 subunit alpha
    Names
    CTC-264K15.6
    skeletal muscle sodium channel alpha subunit
    skeletal muscle voltage-dependent sodium channel type IV alpha subunit
    sodium channel protein skeletal muscle subunit alpha
    sodium channel protein type IV subunit alpha
    sodium channel, voltage-gated, type IV, alpha subunit
    voltage-gated sodium channel subunit alpha Nav1.4

    NCBI Reference Sequences (RefSeq)

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    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_011699.1 RefSeqGene

      Range
      5001..39365
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000334.4 → NP_000325.4  sodium channel protein type 4 subunit alpha

      See identical proteins and their annotated locations for NP_000325.4

      Status: REVIEWED

      Source sequence(s)
      AC127029, AY212253, M81758
      Consensus CDS
      CCDS45761.1
      UniProtKB/Swiss-Prot
      P35499, Q15478, Q16447, Q7Z6B1
      Related
      ENSP00000396320.1, ENST00000435607.3
      Conserved Domains (4) summary
      cd13433
      Location:1296 → 1348
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1048 → 1304
      Ion_trans; Ion transport protein
      pfam06512
      Location:816 → 1026
      Na_trans_assoc; Sodium ion transport-associated
      pfam16905
      Location:1620 → 1675
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      63938554..63972918 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      64809317..64843693 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P35499.4 GenPept UniProtKB/Swiss-Prot:P35499

    Gene LinkOut

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

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