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SCN5A sodium channel, voltage-gated, type V, alpha subunit [ Homo sapiens (human) ]

Gene ID: 6331, updated on 19-Dec-2014
Official Symbol
SCN5Aprovided by HGNC
Official Full Name
sodium channel, voltage-gated, type V, alpha subunitprovided by HGNC
Primary source
HGNC:HGNC:10593
See related
Ensembl:ENSG00000183873; HPRD:02543; MIM:600163; Vega:OTTHUMG00000156166
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
HB1; HB2; HH1; IVF; VF1; HBBD; ICCD; LQT3; SSS1; CDCD2; CMD1E; CMPD2; PFHB1; Nav1.5
Summary
The protein encoded by this gene is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. This protein is found primarily in cardiac muscle and is responsible for the initial upstroke of the action potential in an electrocardiogram. Defects in this gene are a cause of long QT syndrome type 3 (LQT3), an autosomal dominant cardiac disease. Alternative splicing results in several transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
See SCN5A in Epigenomics, MapViewer
Location:
3p21
Exon count:
32
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 3 NC_000003.12 (38548062..38649673, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (38589553..38691164, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene endo/exonuclease (5'-3'), endonuclease G-like Neighboring gene ribosomal protein L18a pseudogene 7 Neighboring gene sodium channel, voltage-gated, type X, alpha subunit Neighboring gene sodium channel, voltage-gated, type XI, alpha subunit

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Professional guidelines

Description
Professional guideline
ACMG 2013

The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in SCN5A that are pathogenic or expected to be pathogenic.

GuidelinePubMed

Associated conditions

Description Tests
Atrial fibrillation, familial, 10
MedGen: C3151464 OMIM: 614022 GeneReviews: Not available
Compare labs
Brugada syndrome 1
MedGen: CN029323 OMIM: 601144 GeneReviews: Brugada Syndrome
Compare labs
Dilated cardiomyopathy 1E Compare labs
Long QT syndrome 3
MedGen: C1859062 OMIM: 603830 GeneReviews: Romano-Ward Syndrome
Compare labs
Paroxysmal familial ventricular fibrillation
MedGen: C0340493 OMIM: 603829 GeneReviews: Not available
Compare labs
Progressive familial heart block type 1A
MedGen: C1879286 OMIM: 113900 GeneReviews: Not available
Compare labs
Sick sinus syndrome 1, autosomal recessive
MedGen: C1837845 OMIM: 608567 GeneReviews: Not available
Compare labs
Sudden infant death syndrome
MedGen: C0038644 OMIM: 272120 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death.
NHGRI GWA Catalog
Common variants at ten loci influence QT interval duration in the QTGEN Study.
NHGRI GWA Catalog
Common variants at ten loci modulate the QT interval duration in the QTSCD Study.
NHGRI GWA Catalog
Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.
NHGRI GWA Catalog
Genetic determinants of P wave duration and PR segment.
NHGRI GWA Catalog
Genome- and phenome-wide analyses of cardiac conduction identifies markers of arrhythmia risk.
NHGRI GWA Catalog
Genome-wide association studies of the PR interval in African Americans.
NHGRI GWA Catalog
Genome-wide association study of electrocardiographic conduction measures in an isolated founder population: Kosrae.
NHGRI GWA Catalog
Genome-wide association study of PR interval.
NHGRI GWA Catalog
Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.
NHGRI GWA Catalog
Several common variants modulate heart rate, PR interval and QRS duration.
NHGRI GWA Catalog
  • Adrenergic signaling in cardiomyocytes, organism-specific biosystem (from KEGG)
    Adrenergic signaling in cardiomyocytes, organism-specific biosystemCardiac myocytes express at least six subtypes of adrenergic receptor (AR) which include three subtypes of beta-AR (beta-1, beta-2, beta-3) and three subtypes of the alpha-1-AR (alpha-1A, alpha-1B, a...
  • Adrenergic signaling in cardiomyocytes, conserved biosystem (from KEGG)
    Adrenergic signaling in cardiomyocytes, conserved biosystemCardiac myocytes express at least six subtypes of adrenergic receptor (AR) which include three subtypes of beta-AR (beta-1, beta-2, beta-3) and three subtypes of the alpha-1-AR (alpha-1A, alpha-1B, a...
  • Axon guidance, organism-specific biosystem (from REACTOME)
    Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
  • Cardiac Progenitor Differentiation, organism-specific biosystem (from WikiPathways)
    Cardiac Progenitor Differentiation, organism-specific biosystemFactors involved in the induction of cardiac differentiation in vitro and in vivo. This model was based on the below two review articles.
  • Developmental Biology, organism-specific biosystem (from REACTOME)
    Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
  • Interaction between L1 and Ankyrins, organism-specific biosystem (from REACTOME)
    Interaction between L1 and Ankyrins, organism-specific biosystemAnkyrins are a family of adaptor proteins that couple membrane proteins such as voltage gated Na+ channels and the Na+/K+ anion exchanger to the spectrin actin cytoskeleton. Ankyrins are encoded by t...
  • L1CAM interactions, organism-specific biosystem (from REACTOME)
    L1CAM interactions, organism-specific biosystemThe L1 family of cell adhesion molecules (L1CAMs) are a subfamily of the immunoglobulin superfamily of transmembrane receptors, comprised of four structurally related proteins: L1, Close Homolog of L...
  • SIDS Susceptibility Pathways, organism-specific biosystem (from WikiPathways)
    SIDS Susceptibility Pathways, organism-specific biosystemIn this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an ov...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ankyrin binding IDA
Inferred from Direct Assay
more info
PubMed 
calmodulin binding IPI
Inferred from Physical Interaction
more info
PubMed 
enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
fibroblast growth factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
ion channel binding IPI
Inferred from Physical Interaction
more info
PubMed 
nitric-oxide synthase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
scaffold protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
voltage-gated sodium channel activity IDA
Inferred from Direct Assay
more info
PubMed 
voltage-gated sodium channel activity involved in cardiac muscle cell action potential IDA
Inferred from Direct Assay
more info
PubMed 
voltage-gated sodium channel activity involved in cardiac muscle cell action potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
Process Evidence Code Pubs
AV node cell to bundle of His cell communication IMP
Inferred from Mutant Phenotype
more info
PubMed 
SA node cell to atrial cardiac muscle cell communication IMP
Inferred from Mutant Phenotype
more info
PubMed 
brainstem development ISS
Inferred from Sequence or Structural Similarity
more info
 
bundle of His cell to Purkinje myocyte communication IMP
Inferred from Mutant Phenotype
more info
PubMed 
cardiac muscle cell action potential involved in contraction IMP
Inferred from Mutant Phenotype
more info
PubMed 
cardiac muscle contraction IMP
Inferred from Mutant Phenotype
more info
PubMed 
cardiac ventricle development ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to calcium ion IDA
Inferred from Direct Assay
more info
PubMed 
cerebellum development ISS
Inferred from Sequence or Structural Similarity
more info
 
membrane depolarization IDA
Inferred from Direct Assay
more info
PubMed 
membrane depolarization during SA node cell action potential ISS
Inferred from Sequence or Structural Similarity
more info
 
membrane depolarization during action potential IDA
Inferred from Direct Assay
more info
PubMed 
membrane depolarization during cardiac muscle cell action potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
neuronal action potential IBA
Inferred from Biological aspect of Ancestor
more info
 
odontogenesis of dentin-containing tooth ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of action potential ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of epithelial cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of sodium ion transport IDA
Inferred from Direct Assay
more info
PubMed 
regulation of atrial cardiac muscle cell membrane depolarization IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of atrial cardiac muscle cell membrane repolarization IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of cardiac muscle cell contraction IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of heart rate IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of heart rate by cardiac conduction IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of sodium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
regulation of ventricular cardiac muscle cell membrane depolarization IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of ventricular cardiac muscle cell membrane repolarization IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to denervation involved in regulation of muscle adaptation ISS
Inferred from Sequence or Structural Similarity
more info
 
sodium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
sodium ion transmembrane transport IMP
Inferred from Mutant Phenotype
more info
PubMed 
sodium ion transport IDA
Inferred from Direct Assay
more info
PubMed 
telencephalon development ISS
Inferred from Sequence or Structural Similarity
more info
 
ventricular cardiac muscle cell action potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
T-tubule IDA
Inferred from Direct Assay
more info
PubMed 
caveola IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with caveola TAS
Traceable Author Statement
more info
PubMed 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
integral component of membrane IDA
Inferred from Direct Assay
more info
PubMed 
intercalated disc IDA
Inferred from Direct Assay
more info
PubMed 
intercalated disc ISS
Inferred from Sequence or Structural Similarity
more info
 
lateral plasma membrane TAS
Traceable Author Statement
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
sarcolemma IDA
Inferred from Direct Assay
more info
PubMed 
voltage-gated sodium channel complex IC
Inferred by Curator
more info
PubMed 
voltage-gated sodium channel complex IDA
Inferred from Direct Assay
more info
PubMed 
Preferred Names
sodium channel protein type 5 subunit alpha
Names
sodium channel protein type 5 subunit alpha
voltage-gated sodium channel subunit alpha Nav1.5
sodium channel protein cardiac muscle subunit alpha
cardiac tetrodotoxin-insensitive voltage-dependent sodium channel alpha subunit

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_008934.1 

    Range
    5000..106611
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_289

mRNA and Protein(s)

  1. NM_000335.4NP_000326.2  sodium channel protein type 5 subunit alpha isoform b

    See proteins identical to NP_000326.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses a different acceptor splice site at one of the coding exons, 3 nt downstream of that used by transcript variant 1. This results in an isoform (b) shorter by just a single aa, compared to isoform a.
    Source sequence(s)
    AB158469, AF482988, AP006241, AY148488, BC051374, BU845010
    Consensus CDS
    CCDS46797.1
    UniProtKB/Swiss-Prot
    Q14524
    UniProtKB/TrEMBL
    Q86V90
    Related
    ENSP00000398266, OTTHUMP00000209282, ENST00000423572, OTTHUMT00000343225
    Conserved Domains (4) summary
    cd13433
    Location:14701522
    Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
    pfam00520
    Location:12401468
    Ion_trans; Ion transport protein
    pfam06512
    Location:9531214
    Na_trans_assoc; Sodium ion transport-associated
    pfam11933
    Location:485668
    DUF3451; Domain of unknown function (DUF3451)
  2. NM_001099404.1NP_001092874.1  sodium channel protein type 5 subunit alpha isoform c

    See proteins identical to NP_001092874.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), also known as hB1, uses an alternate, duplicated coding exon compared to transcript variant 1, resulting in an isoform (c) of the same size, but differing in a few internal aa compared to isoform a.
    Source sequence(s)
    AB158469, AB208866, AF482988, AY038064, BU845010, EF629346
    Consensus CDS
    CCDS46799.1
    UniProtKB/TrEMBL
    H9KVD2
    UniProtKB/Swiss-Prot
    Q14524
    Related
    ENSP00000410257, OTTHUMP00000209281, ENST00000413689, OTTHUMT00000343224
    Conserved Domains (4) summary
    cd13433
    Location:14711523
    Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
    pfam00520
    Location:12411469
    Ion_trans; Ion transport protein
    pfam06512
    Location:9531215
    Na_trans_assoc; Sodium ion transport-associated
    pfam11933
    Location:485668
    DUF3451; Domain of unknown function (DUF3451)
  3. NM_001099405.1NP_001092875.1  sodium channel protein type 5 subunit alpha isoform d

    See proteins identical to NP_001092875.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4), also known as hB2, uses an alternate, duplicated coding exon, and is missing another in-frame, downstream coding exon compared to transcript variant 1, resulting in a shorter isoform (d) missing an internal segment and differing in a few aa, compared to isoform a.
    Source sequence(s)
    AB158469, AB208866, AF482988, AY038064, BU845010, EF629347
    Consensus CDS
    CCDS46798.1
    UniProtKB/TrEMBL
    E9PG18
    UniProtKB/Swiss-Prot
    Q14524
    Related
    ENSP00000416634, ENST00000425664
    Conserved Domains (4) summary
    cd13433
    Location:14531505
    Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
    pfam00520
    Location:12411451
    Ion_trans; Ion transport protein
    pfam06512
    Location:9531215
    Na_trans_assoc; Sodium ion transport-associated
    pfam11933
    Location:485668
    DUF3451; Domain of unknown function (DUF3451)
  4. NM_001160160.1NP_001153632.1  sodium channel protein type 5 subunit alpha isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses an alternate, duplicated exon in the 5' coding region, uses an alternate in-frame splice site in the central coding region, and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The resulting isoform (e) differs at a few internal aa near the N-terminus and lacks a 1-aa and a 32-aa segment, compared to isoform a.
    Source sequence(s)
    AB158469, AF482988, AY038064, BC051374, BC144621
    Consensus CDS
    CCDS54570.1
    UniProtKB/TrEMBL
    E9PHB6
    UniProtKB/Swiss-Prot
    Q14524
    UniProtKB/TrEMBL
    Q86V90
    Related
    ENSP00000399524, OTTHUMP00000209279, ENST00000455624, OTTHUMT00000343215
    Conserved Domains (4) summary
    cd13433
    Location:14701522
    Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
    pfam00520
    Location:12401468
    Ion_trans; Ion transport protein
    pfam06512
    Location:9531214
    Na_trans_assoc; Sodium ion transport-associated
    pfam11933
    Location:485668
    DUF3451; Domain of unknown function (DUF3451)
  5. NM_001160161.1NP_001153633.1  sodium channel protein type 5 subunit alpha isoform f

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) uses an alternate, duplicated exon in the 5' coding region and lacks an alternate in-frame exon in the central coding region, compared to variant 1. The resulting isoform (f) differs at a few internal aa near the N-terminus and lacks a 54-aa segment, compared to isoform a.
    Source sequence(s)
    AB158470, AF482988, AY038064, BC051374, BC140813
    Consensus CDS
    CCDS54569.1
    UniProtKB/TrEMBL
    K4DIA1
    UniProtKB/Swiss-Prot
    Q14524
    UniProtKB/TrEMBL
    Q86V90
    Related
    ENSP00000388797, ENST00000451551
    Conserved Domains (4) summary
    cd13433
    Location:14171469
    Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
    pfam00520
    Location:11871415
    Ion_trans; Ion transport protein
    pfam06512
    Location:9531161
    Na_trans_assoc; Sodium ion transport-associated
    pfam11933
    Location:485668
    DUF3451; Domain of unknown function (DUF3451)
  6. NM_198056.2NP_932173.1  sodium channel protein type 5 subunit alpha isoform a

    See proteins identical to NP_932173.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AB158469, AF482988, AP006241, BU845010, M77235
    Consensus CDS
    CCDS46796.1
    UniProtKB/Swiss-Prot
    Q14524
    Related
    ENSP00000328968, OTTHUMP00000226268, ENST00000333535, OTTHUMT00000377958
    Conserved Domains (4) summary
    cd13433
    Location:14711523
    Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
    pfam00520
    Location:12411469
    Ion_trans; Ion transport protein
    pfam06512
    Location:9531215
    Na_trans_assoc; Sodium ion transport-associated
    pfam11933
    Location:485668
    DUF3451; Domain of unknown function (DUF3451)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000003.12 

    Range
    38548062..38649673
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006713283.1XP_006713346.1  

    See proteins identical to XP_006713346.1

    UniProtKB/Swiss-Prot
    Q14524
    Conserved Domains (4) summary
    cd13433
    Location:14711523
    Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
    pfam00520
    Location:12411469
    Ion_trans; Ion transport protein
    pfam06512
    Location:9531215
    Na_trans_assoc; Sodium ion transport-associated
    pfam11933
    Location:485668
    DUF3451; Domain of unknown function (DUF3451)
  2. XM_006713282.1XP_006713345.1  

    See proteins identical to XP_006713345.1

    UniProtKB/Swiss-Prot
    Q14524
    Conserved Domains (4) summary
    cd13433
    Location:14711523
    Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
    pfam00520
    Location:12411469
    Ion_trans; Ion transport protein
    pfam06512
    Location:9531215
    Na_trans_assoc; Sodium ion transport-associated
    pfam11933
    Location:485668
    DUF3451; Domain of unknown function (DUF3451)
  3. XM_006713284.1XP_006713347.1  

    Conserved Domains (4) summary
    cd13433
    Location:14711523
    Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
    pfam00520
    Location:12411469
    Ion_trans; Ion transport protein
    pfam06512
    Location:9531215
    Na_trans_assoc; Sodium ion transport-associated
    pfam11933
    Location:485668
    DUF3451; Domain of unknown function (DUF3451)

Alternate CHM1_1.1

Genomic

  1. NC_018914.2 

    Range
    38541190..38642759
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

  1. AC_000135.1 

    Range
    38631798..38733467
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)