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Aliases for SCN4A Gene

Aliases for SCN4A Gene

  • Sodium Channel, Voltage Gated, Type IV Alpha Subunit 2 3
  • Sodium Channel, Voltage-Gated, Type IV, Alpha Subunit 2 3
  • Sodium Channel Protein Skeletal Muscle Subunit Alpha 3 4
  • Voltage-Gated Sodium Channel Subunit Alpha Nav1.4 3 4
  • Sodium Channel Protein Type IV Subunit Alpha 3 4
  • HOKPP2 3 6
  • NAC1A 3 6
  • HYPP 3 6
  • SkM1 3 4
  • Skeletal Muscle Voltage-Dependent Sodium Channel Type IV Alpha Subunit 3
  • Sodium Channel Protein Type 4 Subunit Alpha 3
  • Na(V)1.4 3
  • Nav1.4 3
  • HYKPP 3

External Ids for SCN4A Gene

Previous HGNC Symbols for SCN4A Gene

  • HYKPP

Previous GeneCards Identifiers for SCN4A Gene

  • GC17M061653
  • GC17M064442
  • GC17M062356
  • GC17M062489
  • GC17M059369
  • GC17M062015
  • GC17M057383

Summaries for SCN4A Gene

Entrez Gene Summary for SCN4A Gene

  • 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]

GeneCards Summary for SCN4A Gene

SCN4A (Sodium Channel, Voltage Gated, Type IV Alpha Subunit) is a Protein Coding gene. Diseases associated with SCN4A include hypokalemic periodic paralysis, type 2 and paramyotonia congenita. Among its related pathways are L1CAM interactions and Activation of cAMP-Dependent PKA. GO annotations related to this gene include voltage-gated sodium channel activity. An important paralog of this gene is CACNA1D.

UniProtKB/Swiss-Prot for SCN4A Gene

  • This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle

Tocris Summary for SCN4A Gene

  • Voltage-gated sodium channels (NaV) are responsible for action potential initiation and propagation in excitable cells, including nerve, muscle, and neuroendocrine cell types. They are also expressed at low levels in non-excitable cells, where their physiological role is unclear. Structurally, Nav channels are composed of one pore-forming alpha-subunit, which may be associated with either one or more beta-subunits. alpha-subunits are composed for four homologous domains, each of which contains six transmembrane segments. The fourth transmembrane loop (S4) acts as the 'voltage sensor' and is activated by changes in membrane potential. S4 is also involved in channel gating.

Gene Wiki entry for SCN4A Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SCN4A Gene

Genomics for SCN4A Gene

Regulatory Elements for SCN4A Gene

Genomic Location for SCN4A Gene

Start:
63,938,554 bp from pter
End:
63,989,511 bp from pter
Size:
50,958 bases
Orientation:
Minus strand

Genomic View for SCN4A Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SCN4A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SCN4A Gene

Proteins for SCN4A Gene

  • Protein details for SCN4A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P35499-SCN4A_HUMAN
    Recommended name:
    Sodium channel protein type 4 subunit alpha
    Protein Accession:
    P35499
    Secondary Accessions:
    • Q15478
    • Q16447
    • Q7Z6B1

    Protein attributes for SCN4A Gene

    Size:
    1836 amino acids
    Molecular mass:
    208061 Da
    Quaternary structure:
    • Muscle sodium channels contain an alpha subunit and a smaller beta subunit. Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 and SNTB2 (By similarity).

neXtProt entry for SCN4A Gene

Proteomics data for SCN4A Gene at MOPED

Post-translational modifications for SCN4A Gene

  • Phosphorylation at Ser-1328 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.
  • Glycosylation at Asn214, Asn288, Asn291, Asn297, Asn303, Asn315, Asn321, Asn333, Asn362, Asn1191, and Asn1205
  • Modification sites at PhosphoSitePlus

Other Protein References for SCN4A Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for SCN4A Gene

Domains for SCN4A Gene

Gene Families for SCN4A Gene

HGNC:
  • SC :Sodium channels
  • SCN :Voltage-gated ion channels / Sodium channels
IUPHAR :

Graphical View of Domain Structure for InterPro Entry

P35499

UniProtKB/Swiss-Prot:

SCN4A_HUMAN :
  • P35499
Domain:
  • The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position
  • Contains 1 IQ domain.
Family:
  • Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.4/SCN4A subfamily.
genes like me logo Genes that share domains with SCN4A: view

Function for SCN4A Gene

Molecular function for SCN4A Gene

GENATLAS Biochemistry: sodium voltage-gated channel,type IV,alpha polypeptide (see also GH),adult muscle
UniProtKB/Swiss-Prot Function: This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle

Gene Ontology (GO) - Molecular Function for SCN4A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005216 ion channel activity --
GO:0005248 voltage-gated sodium channel activity IBA --
GO:0005515 protein binding --
genes like me logo Genes that share ontologies with SCN4A: view

Phenotypes for SCN4A Gene

genes like me logo Genes that share phenotypes with SCN4A: view

Animal Model Products

miRNA for SCN4A Gene

miRTarBase miRNAs that target SCN4A

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for SCN4A

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targeting and HOMER Transcription for SCN4A Gene

Localization for SCN4A Gene

Subcellular locations from UniProtKB/Swiss-Prot for SCN4A Gene

Membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SCN4A Gene COMPARTMENTS Subcellular localization image for SCN4A gene
Compartment Confidence
plasma membrane 4
extracellular 2
nucleus 1

Gene Ontology (GO) - Cellular Components for SCN4A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001518 voltage-gated sodium channel complex IEA --
GO:0005886 plasma membrane IBA --
GO:0005887 integral component of plasma membrane TAS 1659948
GO:0016020 membrane --
genes like me logo Genes that share ontologies with SCN4A: view

Pathways for SCN4A Gene

genes like me logo Genes that share pathways with SCN4A: view

Gene Ontology (GO) - Biological Process for SCN4A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport --
GO:0006814 sodium ion transport TAS 10218481
GO:0006936 muscle contraction TAS 1338909
GO:0019228 neuronal action potential IBA --
GO:0034765 regulation of ion transmembrane transport IEA --
genes like me logo Genes that share ontologies with SCN4A: view

Compounds for SCN4A Gene

(5) Tocris Compounds for SCN4A Gene

Compound Action Cas Number
Flecainide acetate Cardiac Na+ channel blocker. Antiarrhythmic [54143-56-5]
QX 314 bromide Na+ channel blocker [24003-58-5]
QX 314 chloride Na+ channel blocker [5369-03-9]
Tetrodotoxin Na+ channel blocker [4368-28-9]
Tetrodotoxin citrate Na+ channel blocker; citrate salt of tetrodotoxin (Cat. No. 1078) [18660-81-6]

(1) HMDB Compounds for SCN4A Gene

Compound Synonyms Cas Number PubMed IDs
Sodium
  • Sodium
7440-23-5

(4) Drugbank Compounds for SCN4A Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Diclofenac
  • Diclofenac Acid
15307-86-5 target inhibitor
Flecainide
  • Flecainida [INN-Spanish]
54143-55-4 target inhibitor
Propofol
  • 2,6-Diisopropylphenol
2078-54-8 target inhibitor
Zonisamide
  • Zonisamida [Spanish]
68291-97-4 target inhibitor

(9) IUPHAR Ligand for SCN4A Gene

Ligand Type Action Affinity Pubmed IDs
tetrodotoxin Pore Blocker Antagonist 7.6
AFT-II Gating inhibitor Antagonist 7.5
ATX-II Gating inhibitor Antagonist 7.3
Bc-III Gating inhibitor Antagonist 6.1
mu-conotoxin GIIIA Pore Blocker Antagonist 5.9
mexilitine Pore Blocker Antagonist 3.4
veratridine Activator None
saxitoxin Channel blocker None
batrachotoxin Activator None

(13) Novoseek inferred chemical compound relationships for SCN4A Gene

Compound -log(P) Hits PubMed IDs
sodium 81.5 89
acetazolamide 71.9 1
potassium 58.8 7
chloride 44.2 3
valine 42.3 4

(2) PharmGKB related drug/compound annotations for SCN4A Gene

Drug/compound Annotation
flecainide CA
mexiletine CA
genes like me logo Genes that share compounds with SCN4A: view

Transcripts for SCN4A Gene

mRNA/cDNA for SCN4A Gene

Unigene Clusters for SCN4A Gene

Sodium channel, voltage-gated, type IV, alpha subunit:
Representative Sequences:

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for SCN4A

Primer Products

  • OriGene qSTAR qPCR primer pairs in human,mouse,rat for SCN4A

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for SCN4A Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13 ^ 14a · 14b ^ 15a · 15b ^ 16 ^ 17a · 17b ^ 18a · 18b ^ 19a · 19b ^
SP1: - -
SP2:
SP3: - - - - -
SP4:
SP5:

ExUns: 20 ^ 21 ^ 22 ^ 23 ^ 24
SP1:
SP2:
SP3:
SP4:
SP5:

Relevant External Links for SCN4A Gene

GeneLoc Exon Structure for
SCN4A
ECgene alternative splicing isoforms for
SCN4A

Expression for SCN4A Gene

mRNA expression in normal human tissues for SCN4A Gene

mRNA differential expression in normal tissues according to GTEx for SCN4A Gene

This gene is overexpressed in Muscle - Skeletal (32.1), Adipose - Visceral (Omentum) (5.6), and Adipose - Subcutaneous (4.0).

SOURCE GeneReport for Unigene cluster for SCN4A Gene Hs.46038

genes like me logo Genes that share expressions with SCN4A: view

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein expression and mRNA Expression by UniProt/SwissProt for SCN4A Gene

Orthologs for SCN4A Gene

This gene was present in the common ancestor of animals.

Orthologs for SCN4A Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SCN4A 35
  • 97.32 (n)
  • 96.93 (a)
SCN4A 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SCN4A 35
  • 91.31 (n)
  • 93.66 (a)
SCN4A 36
  • 93 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SCN4A 35
  • 90.4 (n)
  • 94.7 (a)
SCN4A 36
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Scn4a 35
  • 88.54 (n)
  • 92.45 (a)
Scn4a 16
Scn4a 36
  • 92 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SCN4A 36
  • 78 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Scn4a 35
  • 88.91 (n)
  • 92.78 (a)
chicken
(Gallus gallus)
Aves SCN4A 35
  • 79.03 (n)
  • 81.76 (a)
SCN4A 36
  • 72 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SCN4A 36
  • 73 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100492371 35
  • 69.93 (n)
  • 78.22 (a)
zebrafish
(Danio rerio)
Actinopterygii scn4aa 35
  • 69.94 (n)
  • 74.37 (a)
scn4aa 36
  • 69 (a)
OneToMany
scn4ab 36
  • 68 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta NaCP37B 37
  • 55 (a)
NaCP60E 37
  • 62 (a)
para 37
  • 50 (a)
Species with no ortholog for SCN4A:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SCN4A Gene

ENSEMBL:
Gene Tree for SCN4A (if available)
TreeFam:
Gene Tree for SCN4A (if available)

Paralogs for SCN4A Gene

genes like me logo Genes that share paralogs with SCN4A: view

Variants for SCN4A Gene

Sequence variations from dbSNP and Humsavar for SCN4A Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type MAF
rs735621 -- 63,983,358(+) TTCCT(A/G)TGTTC intron-variant
rs758517 -- 63,967,207(+) gagtg(C/T)aatgg intron-variant
rs885633 -- 63,989,907(+) CAAAT(C/T)ACCCT upstream-variant-2KB
rs887283 -- 63,950,461(+) AGCCT(A/G)GGACT intron-variant
rs917557 -- 63,964,198(+) TGGAA(G/T)AATAC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SCN4A Gene

Variant ID Type Subtype PubMed ID
nsv517272 CNV Gain+Loss 19592680
nsv833511 CNV Loss 17160897
nsv908684 CNV Loss 21882294
nsv820272 CNV Loss 19587683
nsv470596 CNV Loss 18288195
esv999259 CNV Loss 20482838
nsv908685 CNV Loss 21882294

Relevant External Links for SCN4A Gene

HapMap Linkage Disequilibrium report
SCN4A
Human Gene Mutation Database (HGMD)
SCN4A
Locus Specific Mutation Databases (LSDB)
SCN4A

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SCN4A Gene

Disorders for SCN4A Gene

(5) OMIM Diseases for SCN4A Gene (603967)

UniProtKB/Swiss-Prot

SCN4A_HUMAN
  • Paramyotonia congenita of von Eulenburg (PMC) [MIM:168300]: An autosomal dominant channelopathy characterized by myotonia, increased by exposure to cold, intermittent flaccid paresis, not necessarily dependent on cold or myotonia, lability of serum potassium, non-progressive nature and lack of atrophy or hypertrophy of muscles. In some patients, myotonia is not increased by cold exposure (paramyotonia without cold paralysis). Patients may have a combination phenotype of PMC and HYPP. {ECO:0000269 PubMed:10369308, ECO:0000269 PubMed:10727489, ECO:0000269 PubMed:1310898, ECO:0000269 PubMed:1316765, ECO:0000269 PubMed:1338909, ECO:0000269 PubMed:15790667, ECO:0000269 PubMed:16786525, ECO:0000269 PubMed:18166706, ECO:0000269 PubMed:19077043, ECO:0000269 PubMed:20076800, ECO:0000269 PubMed:8242056, ECO:0000269 PubMed:8308722, ECO:0000269 PubMed:8388676, ECO:0000269 PubMed:8580427}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Periodic paralysis hypokalemic 2 (HOKPP2) [MIM:613345]: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. {ECO:0000269 PubMed:10599760, ECO:0000269 PubMed:10851391, ECO:0000269 PubMed:10944223, ECO:0000269 PubMed:11558801, ECO:0000269 PubMed:11591859, ECO:0000269 PubMed:18162704, ECO:0000269 PubMed:19118277, ECO:0000269 PubMed:20522878, ECO:0000269 PubMed:21043388}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Periodic paralysis hyperkalemic (HYPP) [MIM:170500]: An autosomal dominant channelopathy characterized by episodic flaccid generalized muscle weakness associated with high levels of serum potassium. Concurrence of myotonia is found in HYPP patients. {ECO:0000269 PubMed:1659668, ECO:0000269 PubMed:1659948, ECO:0000269 PubMed:20076800, ECO:0000269 PubMed:7695243}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Periodic paralysis normokalemic (NKPP) [MIM:170500]: A disorder closely related to hyperkalemic periodic paralysis, but marked by a lack of alterations in potassium levels during attacks of muscle weakness. {ECO:0000269 PubMed:15596759, ECO:0000269 PubMed:18046642, ECO:0000269 PubMed:20522878}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Myotonia SCN4A-related (MYOSCN4A) [MIM:608390]: A phenotypically highly variable myotonia aggravated by potassium loading, and sometimes by cold. Myotonia is characterized by sustained muscle tensing that prevents muscles from relaxing normally. It causes muscle stiffness that can interfere with movement. In some people the stiffness is very mild, while in other cases it may be severe enough to interfere with walking, running, and other activities of daily life. Myotonia SCN4A-related includes myotonia permanens and myotonia fluctuans. In myotonia permanens, the myotonia is generalized and there is a hypertrophy of the muscle, particularly in the neck and the shoulder. Attacks of severe muscle stiffness of the thoracic muscles may be life threatening due to impaired ventilation. In myotonia fluctuans, the muscle stiffness may fluctuate from day to day, provoked by exercise. {ECO:0000269 PubMed:10218481, ECO:0000269 PubMed:16786525, ECO:0000269 PubMed:16832098, ECO:0000269 PubMed:17212350, ECO:0000269 PubMed:17998485, ECO:0000269 PubMed:18203179, ECO:0000269 PubMed:18337100, ECO:0000269 PubMed:19015483, ECO:0000269 PubMed:20076800, ECO:0000269 PubMed:8058156, ECO:0000269 PubMed:9392583}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Myasthenic syndrome, congenital, acetazolamide-responsive (CMSAR) [MIM:614198]: A congenital myasthenic syndrome associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth. The fatigable weakness involves lid-elevator, external ocular, facial, limb and truncal muscles and an decremental response of the compound muscle action potential on repetitive stimulation. {ECO:0000269 PubMed:12766226}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(3) University of Copenhagen DISEASES for SCN4A Gene

(13) Novoseek inferred disease relationships for SCN4A Gene

Disease -log(P) Hits PubMed IDs
paramyotonia congenita 98.1 26
hypokalemic periodic paralysis 95.9 11
hyperkalemic periodic paralysis 95.5 17
periodic paralysis 95.4 17
normokalemic periodic paralysis 94.5 7

Relevant External Links for SCN4A

GeneTests
SCN4A
GeneReviews
SCN4A
Genetic Association Database (GAD)
SCN4A
Human Genome Epidemiology (HuGE) Navigator
SCN4A
genes like me logo Genes that share disorders with SCN4A: view

Publications for SCN4A Gene

  1. Identification of a mutation in the gene causing hyperkalemic periodic paralysis. (PMID: 1659948) Ptacek L.J. … Leppert M.F. (Cell 1991) 2 3 4 23
  2. Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel. (PMID: 1338909) McClatchey A.I. … Brown R.H. Jr. (Nat. Genet. 1992) 3 4 23
  3. The genomic structure of the human skeletal muscle sodium channel gene. (PMID: 1339144) McClatchey A.I. … Gusella J.F. (Hum. Mol. Genet. 1992) 3 4 23
  4. Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita. (PMID: 1310898) McClatchey A.I. … Gusella J.F. (Cell 1992) 3 4 23
  5. Primary structure of the adult human skeletal muscle voltage- dependent sodium channel. (PMID: 1315496) George A.L. Jr. … Barchi R.L. (Ann. Neurol. 1992) 3 4 23

Products for SCN4A Gene

Sources for SCN4A Gene

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