Sodium channel protein type 4 subunit alpha

UniProt P35499 Organism Homo sapiens Gene SCN4A

Also known as: SCN4A

Function

Pore-forming subunit of Nav1.4, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na+ ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues. Highly expressed in skeletal muscles, Nav1.4 generates the action potential crucial for muscle contraction.

Classification

Family (Pfam): PF00520 Ion_trans, PF24609 IQ_SCN5A_C, PF06512 Na_trans_assoc
InterPro: Ion_trans_dom, IQ_SCN5A_C, Na_channel_a4su_mammal, Na_channel_asu, Na_chnl_inactivation_gate, Na_trans_assoc_dom, VGCC_Ca_Na, Volt_channel_dom_sf
Functional cluster: Membrane Transporters & GPCRs

Experimental structures · PDB · 3

6AGF EM 3.20A
6MBA X-ray 1.80A
6MC9 X-ray 3.30A

A predicted model is available from AlphaFold.

Gene Ontology · 8

Disease associations

paramyotonia congenita of Von Eulenburg MONDO:0008195
hyperkalemic periodic paralysis MONDO:0008224
potassium-aggravated myotonia MONDO:0018959
hypokalemic periodic paralysis, type 2 MONDO:0013234
congenital myasthenic syndrome 16 MONDO:0013620
congenital myopathy 22A, classic MONDO:0957247
congenital myopathy 22B, severe fetal MONDO:0957265

Drugs targeting this protein · 59

Neighborhood · nearest proteins

Nearest neighbours of Sodium channel protein type 4 subunit alpha: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Voltage-dependent L-type calcium channel subunit alpha-1S 2 shared papers
Chloride channel protein 1 1 shared papers
Sodium channel protein type 4 subunit alpha 1 shared papers
Sodium channel regulatory subunit beta-1 2 shared papers
Excelsatoxin A 1 shared papers
Transmembrane protein 233 1 shared papers
Transmembrane protein 233 1 shared papers
Sodium channel protein type 9 subunit alpha 1 shared papers
Sodium channel protein type 8 subunit alpha 1 shared papers
Sodium channel protein type 9 subunit alpha 2 shared papers
Sodium channel protein type 9 subunit alpha 1 shared papers
Sodium channel protein type 8 subunit alpha 2 shared papers

Literature · 62 cited papers

Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function. Nat. Commun. · 2023
Case report: Novel SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype. Front. Pediatr. · 2022
Structure of the human voltage-gated sodium channel Nav1.4 in complex with beta1. Science · 2018
A mutation of SCN1B associated with GEFS+ causes functional and maturation defects of the voltage-dependent sodium channel. Hum. Mutat. · 2018
Congenital myopathy with 'corona' fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A. Neuromuscul. Disord. · 2017
A case of non-dystrophic myotonia with concomitant mutations in the SCN4A and CLCN1 genes. J. Neurol. Sci. · 2016
Analysis of protein-coding genetic variation in 60,706 humans. Nature · 2016
Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy. Brain · 2016
A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis. Neurology · 2016
SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy. Hum. Mol. Genet. · 2015
Defective fast inactivation recovery of Nav 1.4 in congenital myasthenic syndrome. Ann. Neurol. · 2015
SCN4A mutation as modifying factor of myotonic dystrophy type 2 phenotype. Neuromuscul. Disord. · 2015
… and 50 more in the literature graph

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