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Aliases for SCN4A Gene

Aliases for SCN4A Gene

  • Sodium Voltage-Gated Channel Alpha Subunit 4 2 3 5
  • 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
  • SkM1 3 4
  • Skeletal Muscle Voltage-Dependent Sodium Channel Type IV Alpha Subunit 3
  • Sodium Channel, Voltage Gated, Type IV Alpha Subunit 2
  • Skeletal Muscle Sodium Channel Alpha Subunit 3
  • Sodium Channel Protein Type 4 Subunit Alpha 3
  • CTC-264K15.6 3
  • Na(V)1.4 3
  • HOKPP2 3
  • Nav1.4 3
  • CMS16 3
  • NAC1A 3
  • HYKPP 3
  • HYPP 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 Voltage-Gated Channel Alpha Subunit 4) is a Protein Coding gene. Diseases associated with SCN4A include Paramyotonia Congenita Of Von Eulenburg and Myotonia, Potassium-Aggravated. Among its related pathways are Cardiac conduction and L1CAM interactions. Gene Ontology (GO) annotations related to this gene include ion channel activity and voltage-gated sodium channel activity. An important paralog of this gene is SCN2A.

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.

Gene Wiki entry for SCN4A Gene

Additional gene information for SCN4A Gene

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

Genomics for SCN4A Gene

GeneHancer (GH) Regulatory Elements for SCN4A Gene

Promoters and enhancers for SCN4A Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH17I063990 Enhancer 1.2 Ensembl ENCODE dbSUPER 550.8 -0.4 -396 1 HDGF RB1 ZSCAN4 SIN3A YBX1 ZBTB7B ZNF48 RAD21 GLIS2 ZNF366 ENSG00000263489 SCN4A CD79B GH1 CSHL1 PRR29
GH17I063987 Enhancer 0.9 FANTOM5 Ensembl ENCODE dbSUPER 558.8 +1.3 1331 2 ZNF512B SCN4A ENSG00000263489 CD79B CSHL1 GH1 PIR61137
GH17I063991 Enhancer 0.8 ENCODE dbSUPER 550.8 +0.1 129 0 ZNF687 RFX1 SUZ12 ZSCAN4 ZBTB7B ZFHX2 MTA3 ZNF512B KLF9 EGR2 ENSG00000263489 SCN4A CD79B GH1 CSHL1
GH17I063972 Promoter/Enhancer 0.7 EPDnew dbSUPER 550.4 +17.2 17180 0.1 PIR61137 SCN4A ENSG00000263489
GH17I064013 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 12.4 -29.9 -29877 12.9 HDGF PKNOX1 FOXA2 SMAD1 MLX ARNT ARID4B SIN3A YBX1 DMAP1 ICAM2 PRR29 DDX5 FTSJ3 SMARCD2 POLG2 CEP95 PLEKHM1P1 ENSG00000265982 DDX42
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around SCN4A on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SCN4A gene promoter:

Genomic Locations for SCN4A Gene

Genomic Locations for SCN4A Gene
chr17:63,938,554-63,990,150
(GRCh38/hg38)
Size:
51,597 bases
Orientation:
Minus strand
chr17:62,015,914-62,050,278
(GRCh37/hg19)

Genomic View for SCN4A Gene

Genes around SCN4A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SCN4A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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. Heterooligomer with SCN2B or SCN4B; disulfide-linked. Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 and SNTB2. Interacts with the conotoxin GVIIJ (PubMed:24497506).

neXtProt entry for SCN4A Gene

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.

Other Protein References for SCN4A Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SCN4A Gene

Domains & Families for SCN4A Gene

Gene Families for SCN4A Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • FDA approved drug targets
  • Predicted membrane proteins
  • Transporters
  • Voltage-gated ion channels

Graphical View of Domain Structure for InterPro Entry

P35499

UniProtKB/Swiss-Prot:

SCN4A_HUMAN :
  • 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.
  • Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.4/SCN4A subfamily.
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.
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 IEA --
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005248 voltage-gated sodium channel activity IBA,TAS --
GO:0005272 sodium channel activity IEA --
genes like me logo Genes that share ontologies with SCN4A: view
genes like me logo Genes that share phenotypes with SCN4A: view

Human Phenotype Ontology for SCN4A Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SCN4A Gene

MGI Knock Outs for SCN4A:

Clone Products

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Transcription Factor Targets and HOMER Transcription for SCN4A Gene

Localization for SCN4A Gene

Subcellular locations from UniProtKB/Swiss-Prot for SCN4A Gene

Cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SCN4A gene
Compartment Confidence
plasma membrane 5
cytoskeleton 2
nucleus 2
extracellular 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Microtubule organizing center (2)
  • Nucleoplasm (2)
See all subcellular structures

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 IEA --
GO:0005887 integral component of plasma membrane TAS 1659948
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with SCN4A: view

Pathways & Interactions for SCN4A Gene

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

Pathways by source for SCN4A Gene

Gene Ontology (GO) - Biological Process for SCN4A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport IEA --
GO:0006811 ion transport IEA --
GO:0006814 sodium ion transport TAS 10218481
GO:0006936 muscle contraction TAS 1338909
GO:0019228 neuronal action potential IBA --
genes like me logo Genes that share ontologies with SCN4A: view

No data available for SIGNOR curated interactions for SCN4A Gene

Drugs & Compounds for SCN4A Gene

(50) Drugs for SCN4A Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, IUPHAR, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Flecainide Approved, Withdrawn Pharma Pore Blocker, Target, inhibitor 43
Zonisamide Approved, Investigational Pharma Target, inhibitor, blocker Antiepileptic with anticonvulsant and mechanistic effect 69
Propofol Approved, Investigational, Vet_approved Pharma Target, inhibitor 1189
Mexiletine Approved, Investigational Pharma blocker 20
Fospropofol Approved, Illicit, Investigational Pharma 21

(8) Additional Compounds for SCN4A Gene - From: HMDB, Novoseek, and IUPHAR

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
sodium
  • Sodium
  • Sodium ion
7440-23-5
mexilitine
Antagonist, Pore Blocker
mu-conotoxin GIIIA
Antagonist, Pore Blocker
4'-Hydroxydiclofenac
  • (O-(2,6-Dichloro-4-hydroxyanilino)phenyl)acetic acid
  • 4'-Hydroxy diclofenac
  • 4'-OH DCF
  • {2-[(2,6-dichloro-4-hydroxyphenyl)amino]phenyl}acetic acid
64118-84-9
4-Hydroxypropofol

(3) Tocris Compounds for SCN4A Gene

Compound Action Cas Number
Amiloride hydrochloride Na+ channel blocker; also I2 imidazoline ligand 2016-88-8
Carbamazepine Inhibitor of neuronal voltage-gated Na+ channels; anticonvulsant 298-46-4
Vinpocetine Na+ channel blocker 42971-09-5

(18) ApexBio Compounds for SCN4A Gene

Compound Action Cas Number
Ambroxol HCl TTX-resistant Na+ currents inhibitor 23828-92-4
Amiloride HCl dihydrate 17440-83-4
Bupivacaine HCl Anaesthetic drug 18010-40-7
Carbamazepine 298-46-4
Dibucaine (Cinchocaine) HCl 1961-12-1
Flecainide acetate Antiarrhythmic drug 54143-56-5
GS967 inhibitor of cardiac late sodium current 1262618-39-2
Ibutilide Fumarate Class III antiarrhythmic agent 122647-32-9
Ouabain 630-60-4
Phenytoin 57-41-0
Phenytoin sodium Sodium channel stabilizer 630-93-3
Procainamide HCl 614-39-1
Procaine HCl 1951-05-8
Propafenone HCl 34183-22-7
Proparacaine HCl 5875-06-9
Riluzole Sodium channel protein inhibitor 1744-22-5
Triamterene 396-01-0
β-Pompilidotoxin Slows Na+ channel inactivation 216064-36-7
genes like me logo Genes that share compounds with SCN4A: view

Drug Products

Transcripts for SCN4A Gene

mRNA/cDNA for SCN4A Gene

(1) REFSEQ mRNAs :
(2) Additional mRNA sequences :
(207) Selected AceView cDNA sequences:
(3) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for SCN4A Gene

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

Clone 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 from GTEx, Illumina, BioGPS, and CGAP SAGE for SCN4A Gene

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

This gene is overexpressed in Muscle - Skeletal (x32.1), Adipose - Visceral (Omentum) (x5.6), and Adipose - Subcutaneous (x4.0).

NURSA nuclear receptor signaling pathways regulating expression of SCN4A Gene:

SCN4A

SOURCE GeneReport for Unigene cluster for SCN4A Gene:

Hs.46038

Evidence on tissue expression from TISSUES for SCN4A Gene

  • Muscle(4.8)
  • Kidney(2.1)
  • Nervous system(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SCN4A Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • cheek
  • chin
  • cranial nerve
  • ear
  • epiglottis
  • eye
  • eyelid
  • face
  • head
  • jaw
  • larynx
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • outer ear
  • pharynx
  • skull
  • tongue
  • tooth
  • vocal cord
Thorax:
  • bronchus
  • chest wall
  • diaphragm
  • esophagus
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • sternum
  • trachea
Abdomen:
  • kidney
  • pancreas
  • stomach
Pelvis:
  • pelvis
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • finger
  • foot
  • forearm
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • blood
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with SCN4A: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners 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 33 34
  • 97.32 (n)
cow
(Bos Taurus)
Mammalia SCN4A 33 34
  • 91.31 (n)
dog
(Canis familiaris)
Mammalia SCN4A 33 34
  • 90.4 (n)
rat
(Rattus norvegicus)
Mammalia Scn4a 33
  • 88.91 (n)
mouse
(Mus musculus)
Mammalia Scn4a 33 16 34
  • 88.54 (n)
oppossum
(Monodelphis domestica)
Mammalia SCN4A 34
  • 78 (a)
OneToOne
chicken
(Gallus gallus)
Aves SCN4A 33 34
  • 79.03 (n)
lizard
(Anolis carolinensis)
Reptilia SCN4A 34
  • 73 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100492371 33
  • 69.93 (n)
zebrafish
(Danio rerio)
Actinopterygii scn4aa 33 34
  • 69.94 (n)
scn4ab 34
  • 68 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta NaCP60E 35
  • 62 (a)
NaCP37B 35
  • 55 (a)
para 35
  • 50 (a)
Species where no ortholog for SCN4A was found in the sources mined by GeneCards:
  • 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 Variation AA Info Type
rs1041781133 likely-benign, not specified, Hyperkalemic Periodic Paralysis Type 1 63,957,315(-) G/A coding_sequence_variant, synonymous_variant
rs1047358376 uncertain-significance, Congenital Myasthenic Syndrome, Recessive, Hypokalemic periodic paralysis, Potassium aggravated myotonia, Hyperkalemic Periodic Paralysis, Paramyotonia congenita of von Eulenburg 63,939,518(-) C/T 3_prime_UTR_variant
rs1057518865 pathogenic, uncertain-significance, Handgrip myotonia, Myotonia, not specified 63,957,443(-) C/T coding_sequence_variant, missense_variant
rs111679484 benign, likely-benign, not specified, Hyperkalemic Periodic Paralysis, Congenital Myasthenic Syndrome, Recessive, Potassium aggravated myotonia, Hypokalemic periodic paralysis, Paramyotonia congenita of von Eulenburg, Hyperkalemic Periodic Paralysis Type 1 63,945,350(-) T/C intron_variant
rs111818485 likely-benign, benign, not specified, Hyperkalemic Periodic Paralysis Type 1 63,963,829(-) T/C intron_variant

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

Variant ID Type Subtype PubMed ID
nsv952357 CNV deletion 24416366
nsv833511 CNV loss 17160897
nsv820272 CNV loss 19587683
nsv517272 CNV gain+loss 19592680
nsv470596 CNV loss 18288195
esv999259 CNV loss 20482838
esv3641022 CNV loss 21293372
esv3641021 CNV gain 21293372

Variation tolerance for SCN4A Gene

Residual Variation Intolerance Score: 49.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.46; 64.16% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SCN4A Gene

Human Gene Mutation Database (HGMD)
SCN4A
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SCN4A

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

Disorders for SCN4A Gene

MalaCards: The human disease database

(26) MalaCards diseases for SCN4A Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search SCN4A in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SCN4A_HUMAN
  • Myasthenic syndrome, congenital, 16 (CMS16) [MIM:614198]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS16 is characterized by 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, ECO:0000269 PubMed:25707578, ECO:0000269 PubMed:26659129}. 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:19347921, ECO:0000269 PubMed:20076800, ECO:0000269 PubMed:27653901, ECO:0000269 PubMed:8058156, ECO:0000269 PubMed:9392583}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Note=SCN4A mutations are the cause of an autosomal recessive neuromuscular disorder characterized by severe fetal hypokinesia, neonatal hypotonia and congenital myopathy of variable severity. The most severe clinical features include reduced or absent fetal movements, in-utero upper and lower limb contractures, talipes and hydrops, and intrauterine or early postnatal death. Mildly affected patients present with generalized hypotonia and weakness at birth or within the first few days of life, mild-to-moderate facial muscle weakness without ptosis, significant early respiratory and feeding difficulties, and skeletal abnormalities of the spine and palate. Symptoms improve over time in patients who survive infancy, resulting in gain of muscle strength and motor skills and concomitant resolution of early respiratory and feeding difficulties. In contrast to other SCN4A-related channelopathies, affected individuals manifest in-utero or neonatal onset of permanent muscle weakness, rather than later-onset episodic muscle weakness. {ECO:0000269 PubMed:26700687}.
  • 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:15318338, ECO:0000269 PubMed:15790667, ECO:0000269 PubMed:16786525, ECO:0000269 PubMed:18166706, ECO:0000269 PubMed:18690054, 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 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}. 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:16890191, ECO:0000269 PubMed:17898326, ECO:0000269 PubMed:18162704, ECO:0000269 PubMed:19118277, ECO:0000269 PubMed:20522878, ECO:0000269 PubMed:21043388, ECO:0000269 PubMed:24549961}. 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.

Additional Disease Information for SCN4A

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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Publications for SCN4A Gene

  1. Identification of a mutation in the gene causing hyperkalemic periodic paralysis. (PMID: 1659948) Ptácek LJ … Leppert MF (Cell 1991) 2 3 4 22 58
  2. New mutation of the Na channel in the severe form of potassium-aggravated myotonia. (PMID: 19347921) Kubota T … Hirose K (Muscle & nerve 2009) 3 4 22 58
  3. Tubular aggregates in paralysis periodica paramyotonica with T704M mutation of SCN4A. (PMID: 19077043) Luan X … Yuan Y (Neuropathology : official journal of the Japanese Society of Neuropathology 2009) 3 4 22 58
  4. Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. (PMID: 19118277) Matthews E … Hanna MG (Neurology 2009) 3 4 22 58
  5. A novel dominant mutation of the Nav1.4 alpha-subunit domain I leading to sodium channel myotonia. (PMID: 19015483) Petitprez S … Burgunder JM (Neurology 2008) 3 4 22 58

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