6uhi

Structural highlights

Disease

RYR1_HUMAN Congenital myopathy with myasthenic-like onset;Moderate multiminicore disease with hand involvement;Congenital multicore myopathy with external ophthalmoplegia;King-Denborough syndrome;Lethal multiple pterygium syndrome;Benign Samaritan congenital myopathy;Malignant hyperthermia of anesthesia;Autosomal recessive centronuclear myopathy;Autosomal dominant centronuclear myopathy;Exercise-induced malignant hyperthermia;Central core disease. Disease susceptibility is associated with variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Defects in RYR1 may be a cause of Samaritan myopathy, a congenital myopathy with benign course. Patients display severe hypotonia and respiratory distress at birth. Unlike other congenital myopathies, the health status constantly improves and patients are minimally affected at adulthood. The disease is caused by variants affecting the gene represented in this entry.

Function

RYR1_HUMAN Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules (PubMed:11741831, PubMed:16163667). Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm (PubMed:18268335). Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).[UniProtKB:E9PZQ0]^{[1] [2] [3]} Q8A5J2_BACTN

References

1. ↑ Bellinger AM, Reiken S, Dura M, Murphy PW, Deng SX, Landry DW, Nieman D, Lehnart SE, Samaru M, LaCampagne A, Marks AR. Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2198-202. PMID:18268335 doi:10.1073/pnas.0711074105
2. ↑ Tilgen N, Zorzato F, Halliger-Keller B, Muntoni F, Sewry C, Palmucci LM, Schneider C, Hauser E, Lehmann-Horn F, Müller CR, Treves S. Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis. Hum Mol Genet. 2001 Dec 1;10(25):2879-87. PMID:11741831 doi:10.1093/hmg/10.25.2879
3. ↑ Monnier N, Kozak-Ribbens G, Krivosic-Horber R, Nivoche Y, Qi D, Kraev N, Loke J, Sharma P, Tegazzin V, Figarella-Branger D, Roméro N, Mezin P, Bendahan D, Payen JF, Depret T, Maclennan DH, Lunardi J. Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility. Hum Mutat. 2005 Nov;26(5):413-25. PMID:16163667 doi:10.1002/humu.20231