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

Gene ID: 6329, updated on 13-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
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Genomic context

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See SCN4A in Genome Data Viewer
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
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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
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
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Paramyotonia congenita of Von Eulenburg
MedGen: C0221055 OMIM: 168300 GeneReviews: Not available
Compare labs
Periodic hyperkalemic paralysis
MedGen: C0238357 OMIM: 170500 GeneReviews: Hyperkalemic Periodic Paralysis
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

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