Human Gene SCN4A (ENST00000435607.3) Description and Page Index
Description: Homo sapiens sodium voltage-gated channel alpha subunit 4 (SCN4A), mRNA. (from RefSeq NM_000334) RefSeq Summary (NM_000334): 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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: M81758.1, AY212253.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000435607.3/ ENSP00000396320.1 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END## Gencode Transcript: ENST00000435607.3 Gencode Gene: ENSG00000007314.12 Transcript (Including UTRs) Position: hg38 chr17:63,938,554-63,972,918 Size: 34,365 Total Exon Count: 24 Strand: - Coding Region Position: hg38 chr17:63,940,771-63,972,841 Size: 32,071 Coding Exon Count: 24
ID:SCN4A_HUMAN DESCRIPTION: RecName: Full=Sodium channel protein type 4 subunit alpha; AltName: Full=SkM1; AltName: Full=Sodium channel protein skeletal muscle subunit alpha; AltName: Full=Sodium channel protein type IV subunit alpha; AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.4; 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. SUBUNIT: 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). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. 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. DISEASE: Defects in SCN4A are the cause of paramyotonia congenita of von Eulenburg (PMC) [MIM:168300]. PMC is 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, nonprogressive 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. DISEASE: Defects in SCN4A are a cause of periodic paralysis hypokalemic type 2 (HOKPP2) [MIM:613345]. It is an autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. DISEASE: Defects in SCN4A are the cause of periodic paralysis hyperkalemic (HYPP) [MIM:170500]. HYPP is 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. DISEASE: Defects in SCN4A are the cause of periodic paralysis normokalemic (NKPP) [MIM:170500]. NKPP is a disorder closely related to hyperkalemic periodic paralysis, but marked by a lack of alterations in potassium levels during attacks of muscle weakness. DISEASE: Defects in SCN4A are the cause of myotonia SCN4A-related (MYOSCN4A) [MIM:608390]. Myotonia is characterized by sustained muscle tensing that prevents muscles from relaxing normally. Myotonia 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. MYOSCN4A is a phenotypically highly variable myotonia aggravated by potassium loading, and often by cold. MYOSCN4A 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. DISEASE: Defects in SCN4A are the cause of a congenital myasthenic syndrome 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. SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.4/SCN4A subfamily. SIMILARITY: Contains 1 IQ domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SCN4A"; WEB RESOURCE: Name=Wikipedia; Note=SCN4A entry; URL="http://en.wikipedia.org/wiki/SCN4A";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00520 - Ion transport protein PF06512 - Sodium ion transport-associated
ModBase Predicted Comparative 3D Structure on P35499
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.