Recombinant Human Sodium channel protein type 4 subunit alpha (SCN4A), partial

1. this study reports the cryo-electron microscopy structure of the human Nav1.4-beta1 complex at 3.2-A resolution. PMID: 30190309
2. R1451 pathogenic mutations shifted the inactivation kinetics and reduced the current density. PMID: 29391559
3. structural basis for gating pore current in periodic paralysis; results reveal pathogenic mechanisms of periodic paralysis at the atomic level and suggest designs of drugs that may prevent ionic leak and provide symptomatic relief from hypokalaemic and normokalaemic periodic paralysis PMID: 29769724
4. Rare SCN4A variants that directly alter NaV1.4 function occur in infants who had died from SIDS. These variants are predicted to significantly alter muscle membrane excitability and compromise respiratory and laryngeal function. PMID: 29605429
5. We report on 3 brothers presenting a peculiar clinical and histopathologic phenotype characterized by facial weakness with ptosis and a mild dystrophic pattern associated with recessive SCN4A mutations. PMID: 28003497
6. Paramyotonia congenita-causing mutation N1366S leads to a gain-of-function change of NaV1.4 gating in response to cold. PMID: 28940424
7. Data suggest that mutation of the sodium channel, voltage-gated, type IV, alpha protein (SCN4A) gene probably underlies the hypokalemic periodic paralysis in the family. PMID: 29419865
8. We identified a novel Nav 1.4 mutation I692M in 14 families out of the 104 genetically identified Hyperkalemic periodic paralysis (HyperPP) families in the Neuromuscular Centre Ulm and is therefore as frequent as I693T (13 families out of 14 HyperPP families) in Germany. Surprisingly, in 13 families, a known polymorphism S906T was also present PMID: 27714768
9. Combining our results with the literature on Chinese populations indicates that 21 mutations in CLCN1 have been associated with myotonia congenital, while 7 mutations in SCN4A have been associated with paramyotonia congenita, 2 mutations in SCN4A have been associated with sodium channel myotonias. PMID: 27415035
10. A rare variant p.Pro1629Leu in SCN4A identified in a patient with a skeletal muscle deficit and intermittent dysphagia. PMID: 28012096
11. Cohort of 30 patients carrying the c.3466G>A p.A1156T mutation in the SCN4A gene showed a consistent phenotype of predominant myalgia, muscle stiffness, and exercise cramps without signs of clinical myotonia, paramyotonia, or periodic paralyses; modest gain in the function of p.A1156T channel in whole-cell patch clamp studies may explain the absence of clinical myotonia PMID: 28330959
12. These data suggest a possible involvement of SCN4A variants in the pathophysiological mechanism underlying the development of a spontaneous or drug-induced type 1 electrocardiographic pattern and the occurrence of malignant arrhythmias in some patients with Brugada syndrome. PMID: 26036855
13. association of the genetic variability of SCN4A with the development of essential tremor PMID: 26427606
14. Computer simulations of the effects of the I693T mutation were introduced in the muscle fiber model by both hyperpolarizing shifts in the Nav1.4 channel activation and a faster recovery from slow channel inactivation PMID: 26494408
15. CACNA1S and SCN4A mutations are relatively rare in patients with hypokalemic periodic paralysis PMID: 26252573
16. Recessive loss-of-function SCN4A mutations were identified in congenital myopathy patients. PMID: 26700687
17. The c.4427 T>C (p.Met1476Thr) mutation of the SCN4A gene contribute to the paramyotonia congenita. PMID: 27060299
18. Mutation analysis in the patient and in child's mother revealed a heterozygous p.N1180I mutation in exon 19 of SCN4A gene. In newborns with stiffness, peripheral contractures and myotonia, the sequence analysis of SCN4A gene should be performed. PMID: 25735906
19. As the result, heterozygous mutations c.2024G>A (R675Q) and c.1333G>A (V445M) of gene SCN4A were identified in the hypokalemic periodic paralysis patient and the paramyotonia congenita family respectively. PMID: 25839108
20. The patient with scn4a mutation exhibited various symptoms that evolved with age, including apneic episodes, tonic muscular contractions during sleep, fluctuating severe episodic myotonia, and finally episodic paralyses. PMID: 25724373
21. Electrophysiological studies of the SCN4A P72L variant showed a hyperpolarizing shift (-5 mV) of the voltage dependence of activation that may increase cell excitability PMID: 25660391
22. A Val1589Met mutation at exon 24 of the SCN4A gene appears in affected subjects with a mild form of paramyotonia, while healthy members had a point mutation at position 1513 at exon 24 of the SCN4A gene PMID: 25755818
23. A homozygous mutation in Nav 1.4 at position 1457 (Arg1457His) was identified in congenital myasthenic syndrome. PMID: 25707578
24. Its M1592V mutation of SCN4A shares a much greater clinical diversity ranging from congenital paramyotonia to periodic paralysis with a longer duration. PMID: 24943082
25. The data indicate that sialic acids attached to both N- and O-glycans residing within the Nav1.4 D1S5-S6 linker modulate channel gating through electrostatic mechanisms PMID: 25450184
26. report the discovery of a novel SCN4A mutation (c.1762A>G; p.I588V) in a patient with myotonia and periodic paralysis, located within the S1 segment of the second domain of the Nav1.4 channel PMID: 25348630
27. SCN4A was functionally affected by R675Q mutation, a possible reason for causing normokalemic periodic paralysis. PMID: 24682880
28. Patients with life-threatening laryngospasm were found to be heterozygous for the same SCN4A mutation. PMID: 25311598
29. The study demonstrates that the hNaV1.4F1705I mutation, which is linked to cold aggravated myotonia, alters the voltage dependence of inactivation and the temperature sensitivity of current kinetics. PMID: 24324661
30. The effect of two single mutations of a critical tyrosine residue in the filter of NaV1.4 on tetrodotoxin binding observed experimentally is reproduced using computational mutagenesis. PMID: 24607901
31. This work reveals a novel mechanism of disrupted S4 translocation for hypokalaemic periodic paralysis mutations at arginine residues located below the gating pore constriction of the voltage sensor module. PMID: 24549961
32. Non-dystrophic myotonias are characterised by muscle stiffness during voluntary movement owing to delayed skeletal muscle relaxation caused by mutation in the SCN4A skeletal muscle channel genes. PMID: 23417379
33. Non-dystrophic myotonias are rare diseases caused by mutations in skeletal muscle SCN4A. PMID: 23771340
34. genetic study showed missense mutation (R1448C) in the voltage-gated sodium channel, type IV, alpha subunit PMID: 23420899
35. Analyses of SCN4A, a key player in myotonia, have revealed parallels between its slow-inactivation and myotonic warm-up, which suggest that SCN4A is critical not only in producing the myotonic reaction, but also in mediating the warm-up. PMID: 23381896
36. Nav1.4 N440K mutation causes a gain of function consistent with skeletal muscle hyperexcitability as observed in individuals with the mutation. PMID: 22914841
37. Cooling can augment the disruption of the voltage dependence of fast inactivation by mutant M1476I/Nav1.4 channels PMID: 22250216
38. The patient presented a marked warm-up phenomenon of myotonia but the repeated short exercise test suggested mutations of the sodium channel. PMID: 22617007
39. We found significant ocular involvement in a family with a mutation in SCN4A. PMID: 22653516
40. A minority of sporadic periodic paralysis patients studied have de novo CACNA1S or SCN4A mutations and may have a variant of familial periodic paralysis. PMID: 21841462
41. Substitutions at position 799 of the Nav1.4 channel favor the channel open state with sustained activity leading to hyperexcitability of laryngeal muscles that could be lethal during infancy. PMID: 21521764
42. L1436P mutation in the SCN4A gene causes a sodium channel myotonia with an atypical clinical presentation, characterized by late onset painful cold-aggravated myotonia PMID: 21664816
43. This study demonistrated that mutation of Met1592Val in the SCN4A gene is associated with aggressive development of paralysis periodica paramyotonia characterized by severe vacuolar myopathy. PMID: 21665479
44. The skeletal muscle alpha-subunit NaV1.4 was transiently expressed in wild-type Chinese hamster ovary (CHO) cells PMID: 21606664
45. ranolazine interacts with the open state and stabilizes the inactivated state(s) of Na(v)1.4 channels, causes voltage- and use-dependent block of I(Na) and suppresses persistent I(Na) PMID: 21317558
46. Anthopleurin elicited opposing effects on the gating mode, kinetics and charge immobilized during open- versus closed-state fast inactivation of Nav1.4 channels. PMID: 21099342
47. study detected the SCN4A R672H mutation in one hypokalemic periodic paralysis Turkish family PMID: 21043388
48. Severe neonatal episodic laryngospasm is a new phenotype caused by a sodium channelopathy, which can be alleviated by channel blockers. PMID: 20713951
49. electrostatic network interactions between S2 and other transmembrane segments within Na(v)1.4D4 are similar to but not identical to those proposed for K+ channels PMID: 19881885
50. This study describes the first cases of homozygosity for two missense mutations in the SCN4A gene which increases severity of muscle channelopathies. PMID: 19882638

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HGNC: 10591

OMIM: 168300

KEGG: hsa:6329

STRING: 9606.ENSP00000396320

UniGene: Hs.46038