Recombinant Human Voltage-dependent L-type calcium channel subunit alpha-1S (CACNA1S), partial

1. Cav1.1 is specified for the excitation-contraction coupling of skeletal muscles, and has been a prototype in the structural investigations of Cav channels. This article summarized the recent advances in the structural elucidation of Cav1.1 and the mechanistic insights derived from the 3.6 A structure obtained using single-particle, electron cryomicroscopy. PMID: 29594856
2. he ryanodine receptor 1 (RyR1) is mainly expressed in the sarcoplasmic reticulum (SR) of skeletal muscle and is a calcium release channel which is coupled to the dihydropyridine receptor (CACNA1S) in the T-tubule of the sarcolemma. PMID: 27147545
3. V876E mutation generates a gating pore current that carries strong resting Na(+) inward currents in physiological conditions that are likely responsible for the severe hypokalemic periodic paralysis associated with this mutation. PMID: 29114033
4. review of the pharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia susceptibility type 5 (MHS5); several mutations are known to be risk factors for increased susceptibility; at present, one or at most six CACNA1S mutations display significant linkage or association either to clinically diagnosed MH or to MHS PMID: 28011884
5. Study used structure modeling and MD simulations to predict pathogenic omega-currents in CaV1.1 and CaV1.3 Ca(2+) channels bearing several S4 charge mutations: omega-currents conducted in resting state, but not during voltage-sensing domain activation. Mechanism responsible depends on the number of charges in S4, the position of the mutated S4 charge and countercharges, and the nature of the replacing amino acid. PMID: 28978442
6. Study identified by exome sequencing both recessive and dominant CACNA1S mutations as a cause of a congenital myopathy characterized by peculiar morphological hallmarks in a cohort of 11 patients from 7 families. PMID: 28012042
7. whole-exome next-generation sequencing was used to identify a mutation in the CACNA1S gene, R900S, which is a rare mutation associated with hypokalemic periodic paralysis; study provides further evidence for the phenotypic variation and pharmacogenomics of hypokalemic periodic paralysis PMID: 26433613
8. These results provide new insights into the role of muscle-specific proteins on the structural arrangement of alpha1S intracellular loops and point to a new conformational effect of the beta1a subunit in supporting skeletal muscle excitation-contraction coupling. PMID: 27129199
9. CACNA1S and SCN4A mutations are relatively rare in patients with hypokalemic periodic paralysis PMID: 26252573
10. The authors found one and three rare variants of unknown significance in CACNA1S in the Malignant Hyperthermia and Exertional Heat cohorts PMID: 25658027
11. Defects in the genes coding for the skeletal muscle ryanodine receptor and alpha 1 subunit of the dihydropyridine receptor (CACNA1S) have been identified as causative for malignant hyperthermia. PMID: 25735680
12. Aberrant splicing of Cav 1.1 may alter intracellular Ca(2+) signalling in myotonic dystrophy 1 and 2 myotubes. The differing dysregulation of intracellular Ca(2+) handling in DM1 and DM2 may explain their distinct sarcolemmal hyperexcitabilities. PMID: 23888875
13. Exome sequencing revealed one rare cacna1s nonsynonymous variant in a family with malignant hyperthermia PMID: 24013571
14. Data indicate that the presence of either one of these JP-45 variants decreased the sensitivity of the dihydropyridine receptor DHPR to activation. PMID: 22927026
15. Affected members of a 5-generation Chinese family with hypokalemic periodic paralysis patients had a novel His916Gln mutation in all male HypoPP patients of the family. Penetrance of the mutation was complete in male carriers, but not female carriers. PMID: 21845430
16. Misregulated splicing and altered gating of Ca(V)1.1 calcium channel is associated with muscle weakness in myotonic dystrophy. PMID: 22140091
17. A novel mutation in the CACNA1S gene--p.Arg900Gly--is found in a patient with hypokalemic periodic paralysis; this mutation is subsequently found to affect some of the patient's other family members. PMID: 21855088
18. All familial periodic paralysis patients studied have mutations in either CACNA1S or SCN4A, but only 4 sporadic periodic paralysis patients have de novo mutations in CACNA1S (R1239H) and SCN4A (R669x2, R1135H). PMID: 21841462
19. Three SNPs of CACNA1S gene exon 11 were found but could not be associated with thyrotoxic hypokalemic periodic paralysis in people of Han Nationality in Sichuan. PMID: 21774221
20. Expression of transgenic variants of dihydropyridine receptor (alpha1DHPR) subunit leads to replacement of native channels interacting with ryanodine receptor 1 (RyR1), demonstrating molecular remodelling in adult skeletal muscle fibers. PMID: 21262876
21. Mutations in the affected genes cause Malignant Hyperthermia. PMID: 21248738
22. All individuals in the Italian family with malignant hyperthermia showed cosegregation of informative markers close to the voltage-dependent Ca2+ channel alpha-1S-subunit gene. Sequence analysis showed a c.4060A>T transversion. PMID: 20861472
23. Results identify a new mutation in CACNA1S and expand the spectrum of CACNA1S mutations associated with HypoPP. PMID: 19779499
24. Ca(V)1.1 Delta 29 splice variant revealed the structural bases underlying the specific gating properties of skeletal muscle Ca(2+) channels, and suggests the existence of a distinct mode of excitation-contraction coupling in developing muscle PMID: 19134469
25. polymorphisms in the CACNA1S gene is associated with Malignant Hyperthermia PMID: 12636044
26. a mutation of the CACNA1S gene may have a role in hypokalemic periodic paralysis PMID: 15716625
27. a novel Arg528Gly mutation in the CACNA1S gene that causes Hypokalemic periodic paralysis in a Chinese family PMID: 15726306
28. We propose that CACNA1S mutations may comprise a previously unrecognized genetic risk factor in a greater spectrum of motor unit disorders including amyotrophic lateral sclerosis. PMID: 17587224
29. A Polish three-generation family with hypokalemic periodic paralysis and a mutation in CACNA1S is investigated. PMID: 18229654
30. All mutations affected CACNA1S arginine residues, consistent with the gating pore cation leak hypothesis of hypokalemic periodic paralysis. Arginine mutations in S4 segments underlie 90% of hypokalemic periodic paralysis cases. PMID: 19118277
31. A novel method to detect autoantibodies to dihydropyridine receptor (DHPR), found increased DHPR antibody in myasthenia gravis patients compared to controls. PMID: 19187971
32. The study identified a single potentially pathogenic change in CACNA1S (p.Arg174Trp), and highlights that the haplotype structure across CACNA1S is diverse, with a high degree of variability PMID: 19825159

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HGNC: 1397

OMIM: 114208

KEGG: hsa:779

STRING: 9606.ENSP00000355192

UniGene: Hs.1294