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]
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.
Subcellular Location:
Membrane.
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.
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.
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.
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.
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.
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.
Contains 1 IQ domain.
SWISS:
P35499
Gene ID:
6329
Database links:
Entrez Gene: 6329 Human
Entrez Gene: 110176 Mouse
Entrez Gene: 25722 Rat
Omim: 603967 Human
SwissProt: P35499 Human
SwissProt: Q9ER60 Mouse
SwissProt: P15390 Rat
Unigene: 9238 Human
Unigene: 432528 Mouse
Unigene: 9700 Rat
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