RYR1RYR

Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm. 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)

開啟資料庫紀錄 ↗

Ca(2+)(in) = Ca(2+)(out)

開啟資料庫紀錄 ↗

Homotetramer. Can also form heterotetramers with RYR2 (By similarity). Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1). Repeated very high-level exercise decreases interaction with PDE4D and protein phosphatase 1 (PP1). Interacts with CALM; CALM with bound calcium inhibits the RYR1 channel activity. Interacts with S100A1. Interacts with FKBP1A; this stabilizes the closed conformation of the channel. Interacts with CACNA1S; interaction with CACNA1S is important for activation of the RYR1 channel. Interacts with CACNB1. Interacts with TRDN and ASPH; these interactions stimulate RYR1 channel activity. Interacts with SELENON (By similarity). Interacts with scorpion calcins (AC P0DPT1; AC P0DM30; AC A0A1L4BJ42; AC P59868; AC P60254; AC B8QG00; AC L0GBR1; AC P60252; AC P60253) (By similarity)

開啟資料庫紀錄 ↗

Sarcoplasmic reticulum membrane / Multi-pass membrane protein; The number of predicted transmembrane domains varies between orthologs. Both N-terminus and C-terminus are cytoplasmic

開啟資料庫紀錄 ↗

Malignant hyperthermia 1 MHS1 Autosomal dominant pharmacogenetic disorder of skeletal muscle and is one of the main causes of death due to anesthesia. In susceptible people, an MH episode can be triggered by all commonly used inhalational anesthetics such as halothane and by depolarizing muscle relaxants such as succinylcholine. The clinical features of the myopathy are hyperthermia, accelerated muscle metabolism, contractures, metabolic acidosis, tachycardia and death, if not treated with the postsynaptic muscle relaxant, dantrolene. Susceptibility to MH can be determined with the 'in vitro' contracture test (IVCT): observing the magnitude of contractures induced in strips of muscle tissue by caffeine alone and halothane alone. Patients with normal response are MH normal (MHN), those with abnormal response to caffeine alone or halothane alone are MH equivocal (MHE(C) and MHE(H) respectively). Disease susceptibility is associated with variants affecting the gene represented in this entry MIM: 145600

開啟資料庫紀錄 ↗

Congenital myopathy 1A, autosomal dominant, with susceptibility to malignant hyperthermia CMYO1A An autosomal dominant myopathy characterized by hypotonia and proximal muscle weakness primarily affecting the lower limbs, beginning in infancy or early childhood. Some patients manifest later onset of symptoms. The clinical course of the disorder is usually slow or non-progressive in adulthood, and the severity of the symptoms is variable. Affected individuals typically show delayed motor development and usually achieve independent walking, although many have difficulty running or climbing stairs. Additional features often include mild facial weakness, joint laxity, shoulder girdle weakness, and skeletal manifestations, such as dislocation of the hips, foot deformities, scoliosis, and Achilles tendon contractures. Microscopic examination of affected skeletal muscle reveals a predominance of type I fibers containing amorphous-looking areas (cores) that do not stain with oxidative and phosphorylase histochemical techniques. Additional pathologic findings may also be observed on muscle biopsy. CMYO1A affected individuals are at risk for malignant hyperthermia, and both disorders may be present in the same family. The disease is caused by variants affecting the gene represented in this entry MIM: 117000

開啟資料庫紀錄 ↗

Congenital myopathy 1B, autosomal recessive CMYO1B An autosomal recessive myopathy characterized by severe hypotonia and generalized muscle weakness and atrophy apparent soon after birth or in early childhood. Affected individuals show delayed motor development, proximal muscle weakness with axial and shoulder girdle involvement, difficulty walking or running, external ophthalmoplegia, and bulbar weakness often resulting in feeding difficulties and respiratory insufficiency. Disease severity is variable. Some affected individuals show symptoms in utero, including reduced fetal movements, polyhydramnios, and intrauterine growth restriction. Some patients have lethal fetal akinesia with death in utero. Muscle biopsy can show variable findings, including multiple and poorly circumscribed areas of sarcomere disorganization and mitochondria depletion (areas termed minicores). Typically, no dystrophic signs, such as muscle fiber necrosis or regeneration or significant endomysial fibrosis, are present. The disease is caused by variants affecting the gene represented in this entry MIM: 255320

開啟資料庫紀錄 ↗

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

開啟資料庫紀錄 ↗

King-Denborough syndrome KDS An autosomal dominant disorder characterized by the triad of dysmorphic features, congenital myopathy, and susceptibility to malignant hyperthermia. Variable expressivity has been reported in several cases. The disease is caused by variants affecting the gene represented in this entry MIM: 619542

開啟資料庫紀錄 ↗