SCN4A
entrez
6329
canonical
uniprot
P35499
canonical
ensembl
ENSG00000007314
resolver
ensp
ENSP00000396320
resolver
enst
ENST00000435607
resolver
genesymbol
SCN4A
resolver
hgnc
HGNC:10591
resolver
uniprot
Q15478
resolver
uniprot
Q16447
resolver
uniprot
Q7Z6B1
resolver
uniprot_entry
SCN4A_HUMAN
resolver
uniprot_sec
Q15478
resolver
uniprot_sec
Q16447
resolver
uniprot_sec
Q7Z6B1
resolver
activity_regulation
ACTIVITY REGULATION: The channel is inhibited by tetrodotoxin and saxitoxin (PubMed:30190309). Inhibited by the conotoxin GVIIJ (PubMed:24497506). {ECO:0000269|PubMed:24497506, ECO:0000269|PubMed:30190309}.
uniprot
proteins
amino_acid_sequence
MARPSLCTLVPLGPECLRPFTRESLAAIEQRAVEEEARLQRNKQMEIEEPERKPRSDLEAGKNLPMIYGDPPPEVIGIPLEDLDPYYSNKKTFIVLNKGKAIFRFSATPALYLLSPFSVVRRGAIKVLIHALFSMFIMITILTNCVFMTMSDPPPWSKNVEYTFTGIYTFESLIKILARGFCVDDFTFLRDPWNWLDFSVIMMAYLTEFVDLGNISALRTFRVLRALKTITVIPGLKTIVGALIQSVKKLSDVMILTVFCLSVFALVGLQLFMGNLRQKCVRWPPPFNDTNTTWYSNDTWYGNDTWYGNEMWYGNDSWYANDTWNSHASWATNDTFDWDAYISDEGNFYFLEGSNDALLCGNSSDAGHCPEGYECIKTGRNPNYGYTSYDTFSWAFLALFRLMTQDYWENLFQLTLRAAGKTYMIFFVVIIFLGSFYLINLILAVVAMAYAEQNEATLAEDKEKEEEFQQMLEKFKKHQEELEKAKAAQALEGGEADGDPAHGKDCNGSLDTSQGEKGAPRQSSSGDSGISDAMEELEEAHQKCPPWWYKCAHKVLIWNCCAPWLKFKNIIHLIVMDPFVDLGITICIVLNTLFMAMEHYPMTEHFDNVLTVGNLVFTGIFTAEMVLKLIAMDPYEYFQQGWNIFDSIIVTLSLVELGLANVQGLSVLRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKECVCKIALDCNLPRWHMHDFFHSFLIVFRILCGEWIETMWDCMEVAGQAMCLTVFLMVMVIGNLVVLNLFLALLLSSFSADSLAASDEDGEMNNLQIAIGRIKLGIGFAKAFLLGLLHGKILSPKDIMLSLGEADGAGEAGEAGETAPEDEKKEPPEEDLKKDNHILNHMGLADGPPSSLELDHLNFINNPYLTIQVPIASEESDLEMPTEEETDTFSEPEDSKKPPQPLYDGNSSVCSTADYKPPEEDPEEQAEENPEGEQPEECFTEACVQRWPCLYVDISQGRGKKWWTLRRACFKIVEHNWFETFIVFMILLSSGALAFEDIYIEQRRVIRTILEYADKVFTYIFIMEMLLKWVAYGFKVYFTNAWCWLDFLIVDVSIISLVANWLGYSELGPIKSLRTLRALRPLRALSRFEGMRVVVNALLGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYYCINTTTSERFDISEVNNKSECESLMHTGQVRWLNVKVNYDNVGLGYLSLLQVATFKGWMDIMYAAVDSREKEEQPQYEVNLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKLGGKDIFMTEEQKKYYNAMKKLGSKKPQKPIPRPQNKIQGMVYDLVTKQAFDITIMILICLNMVTMMVETDNQSQLKVDILYNINMIFIIIFTGECVLKMLALRQYYFTVGWNIFDFVVVILSIVGLALSDLIQKYFVSPTLFRVIRLARIGRVLRLIRGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYSIFGMSNFAYVKKESGIDDMFNFETFGNSIICLFEITTSAGWDGLLNPILNSGPPDCDPNLENPGTSVKGDCGNPSIGICFFCSYIIISFLIVVNMYIAIILENFNVATEESSEPLGEDDFEMFYETWEKFDPDATQFIAYSRLSDFVDTLQEPLRIAKPNKIKLITLDLPMVPGDKIHCLDILFALTKEVLGDSGEMDALKQTMEEKFMAANPSKVSYEPITTTLKRKHEEVCAIKIQRAYRRHLLQRSMKQASYMYRHSHDGSGDDAPEKEGLLANTMSKMYGHENGNSSSPSPEEKGEAGDAGPTMGLMPISPSDTAWPPAPPPGQTVRPGVKESLV
uniprot
proteins
disease_involvement
DISEASE: Paramyotonia congenita (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 variants affecting the gene represented in this entry.; DISEASE: 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 variants affecting the gene represented in this entry.; DISEASE: 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 variants affecting the gene represented in this entry.; DISEASE: 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 variants affecting the gene represented in this entry.; DISEASE: 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 variants affecting the gene represented in this entry.; DISEASE: 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 variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy 22A, classic (CMYO22A) [MIM:620351]: A form of congenital myopathy, a clinically and genetically heterogeneous group of muscle disorders characterized by hypotonia and muscle weakness apparent at birth, and specific pathological features on muscle biopsy. CMYO22A is an autosomal recessive form characterized by fetal hypokinesia, polyhydramnios, and severe neonatal hypotonia associated with respiratory insufficiency. Affected individuals who survive the neonatal period have delayed motor development, difficulty walking, proximal muscle weakness of the upper and lower limbs, facial and neck muscle weakness, easy fatigability, and mild limb contractures or foot deformities. {ECO:0000269|PubMed:26700687, ECO:0000269|PubMed:28262468, ECO:0000269|PubMed:36090556}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy 22B, severe fetal (CMYO22B) [MIM:620369]: A severe congenital myopathy, a clinically and genetically heterogeneous group of muscle disorders characterized by hypotonia and muscle weakness apparent at birth, and specific pathological features on muscle biopsy. CMYO22B is an autosomal recessive form characterized by onset in utero. Affected individuals show fetal akinesia, and develop fetal hydrops with pulmonary hypoplasia, severe joint contractures, and generalized muscle hypoplasia. Death occurs in utero or soon after birth. {ECO:0000269|PubMed:26700687}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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 (PubMed:12766226, PubMed:15318338, PubMed:16890191, PubMed:17898326, PubMed:18690054, PubMed:19347921, PubMed:25707578, PubMed:26659129, PubMed:26700687, PubMed:29992740, PubMed:30190309). Highly expressed in skeletal muscles, Nav1.4 generates the action potential crucial for muscle contraction (PubMed:16890191, PubMed:19347921, PubMed:25707578, PubMed:26659129, PubMed:26700687). {ECO:0000269|PubMed:12766226, ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:16890191, ECO:0000269|PubMed:17898326, ECO:0000269|PubMed:18690054, ECO:0000269|PubMed:19347921, ECO:0000269|PubMed:25707578, ECO:0000269|PubMed:26659129, ECO:0000269|PubMed:26700687, ECO:0000269|PubMed:29992740, ECO:0000269|PubMed:30190309}.
uniprot
proteins
mass_dalton
208061
uniprot
proteins
protein_family
Nav1.4/SCN4A subfamily
uniprot
proteins
protein_family
Sodium channel (TC 1.A.1.10) family
uniprot
proteins
pubmed
10218481
uniprot
proteins
pubmed
10369308
uniprot
proteins
pubmed
10599760
uniprot
proteins
pubmed
10727489
uniprot
proteins
pubmed
10851391
uniprot
proteins
pubmed
10944223
uniprot
proteins
pubmed
11558801
uniprot
proteins
pubmed
11591859
uniprot
proteins
pubmed
12766226
uniprot
proteins
pubmed
1310396
uniprot
proteins
pubmed
1310898
uniprot
proteins
pubmed
1315496
uniprot
proteins
pubmed
1316765
uniprot
proteins
pubmed
1338909
uniprot
proteins
pubmed
1339144
uniprot
proteins
pubmed
15318338
uniprot
proteins
pubmed
15596759
uniprot
proteins
pubmed
15790667
uniprot
proteins
pubmed
1659668
uniprot
proteins
pubmed
1659948
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
16786525
uniprot
proteins
pubmed
16832098
uniprot
proteins
pubmed
16890191
uniprot
proteins
pubmed
17212350
uniprot
proteins
pubmed
17898326
uniprot
proteins
pubmed
17998485
uniprot
proteins
pubmed
18046642
uniprot
proteins
pubmed
18162704
uniprot
proteins
pubmed
18166706
uniprot
proteins
pubmed
18203179
uniprot
proteins
pubmed
18337100
uniprot
proteins
pubmed
18690054
uniprot
proteins
pubmed
19015483
uniprot
proteins
pubmed
19077043
uniprot
proteins
pubmed
19118277
uniprot
proteins
pubmed
19347921
uniprot
proteins
pubmed
20076800
uniprot
proteins
pubmed
20522878
uniprot
proteins
pubmed
21043388
uniprot
proteins
pubmed
24497506
uniprot
proteins
pubmed
24549961
uniprot
proteins
pubmed
25660391
uniprot
proteins
pubmed
25707578
uniprot
proteins
pubmed
26427606
uniprot
proteins
pubmed
26659129
uniprot
proteins
pubmed
26700687
uniprot
proteins
pubmed
27535533
uniprot
proteins
pubmed
27653901
uniprot
proteins
pubmed
28262468
uniprot
proteins
pubmed
29992740
uniprot
proteins
pubmed
30190309
uniprot
proteins
pubmed
36090556
uniprot
proteins
pubmed
37117223
uniprot
proteins
pubmed
7695243
uniprot
proteins
pubmed
8058156
uniprot
proteins
pubmed
8242056
uniprot
proteins
pubmed
8308722
uniprot
proteins
pubmed
8388676
uniprot
proteins
pubmed
8580427
uniprot
proteins
pubmed
9266738
uniprot
proteins
pubmed
9392583
uniprot
proteins
sequence_length
1836
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12766226, ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:16890191, ECO:0000269|PubMed:17898326, ECO:0000269|PubMed:18690054, ECO:0000269|PubMed:19347921, ECO:0000269|PubMed:25707578, ECO:0000269|PubMed:26659129, ECO:0000269|PubMed:26700687, ECO:0000269|PubMed:29992740, ECO:0000269|PubMed:30190309}; Multi-pass membrane protein {ECO:0000269|PubMed:30190309}.
uniprot
proteins
transmembrane_region
TRANSMEM 132..150; /note="Helical; Name=S1 of repeat I"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 158..178; /note="Helical; Name=S2 of repeat I"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 193..210; /note="Helical; Name=S3 of repeat I"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 217..233; /note="Helical; Name=S4 of repeat I"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 253..272; /note="Helical; Name=S5 of repeat I"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 424..444; /note="Helical; Name=S6 of repeat I"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 579..597; /note="Helical; Name=S1 of repeat II"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 609..628; /note="Helical; Name=S2 of repeat II"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 643..662; /note="Helical; Name=S3 of repeat II"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 665..682; /note="Helical; Name=S4 of repeat II"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 699..717; /note="Helical; Name=S5 of repeat II"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 779..797; /note="Helical; Name=S6 of repeat II"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1033..1050; /note="Helical; Name=S1 of repeat III"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1064..1082; /note="Helical; Name=S2 of repeat III"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1097..1115; /note="Helical; Name=S3 of repeat III"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1124..1142; /note="Helical; Name=S4 of repeat III"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1160..1179; /note="Helical; Name=S5 of repeat III"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1270..1291; /note="Helical; Name=S6 of repeat III"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1355..1372; /note="Helical; Name=S1 of repeat IV"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1384..1402; /note="Helical; Name=S2 of repeat IV"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1415..1432; /note="Helical; Name=S3 of repeat IV"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1446..1462; /note="Helical; Name=S4 of repeat IV"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1482..1499; /note="Helical; Name=S5 of repeat IV"; /evidence="ECO:0000269|PubMed:30190309"; TRANSMEM 1575..1597; /note="Helical; Name=S6 of repeat IV"; /evidence="ECO:0000269|PubMed:30190309
uniprot
proteins