RYR1

Highest pathogenic variant AF is 0.00021201343

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000359596

Coding exons

106

Length

153866

Individuals with no LoFs

125404

Homozygous LoFs

0

Heterozygous LoFs

344

Defined

125748

p

0.00137

Function

FUNCTION: 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). {ECO:0000250|UniProtKB:E9PZQ0, ECO:0000269|PubMed:18268335, ECO:0000305|PubMed:11741831, ECO:0000305|PubMed:16163667}.;

Disease

DISEASE: Malignant hyperthermia 1 (MHS1) [MIM:145600]: 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). {ECO:0000269|PubMed:10051009, ECO:0000269|PubMed:10484775, ECO:0000269|PubMed:10612851, ECO:0000269|PubMed:10823104, ECO:0000269|PubMed:10888602, ECO:0000269|PubMed:11241852, ECO:0000269|PubMed:11389482, ECO:0000269|PubMed:11525881, ECO:0000269|PubMed:11575529, ECO:0000269|PubMed:11928716, ECO:0000269|PubMed:12059893, ECO:0000269|PubMed:12066726, ECO:0000269|PubMed:12123492, ECO:0000269|PubMed:12208234, ECO:0000269|PubMed:12411788, ECO:0000269|PubMed:12709367, ECO:0000269|PubMed:12883402, ECO:0000269|PubMed:1354642, ECO:0000269|PubMed:14732627, ECO:0000269|PubMed:14985404, ECO:0000269|PubMed:15221887, ECO:0000269|PubMed:15448513, ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:1774074, ECO:0000269|PubMed:19191329, ECO:0000269|PubMed:19685112, ECO:0000269|PubMed:20142353, ECO:0000269|PubMed:20681998, ECO:0000269|PubMed:23558838, ECO:0000269|PubMed:24013571, ECO:0000269|PubMed:26115329, ECO:0000269|PubMed:26381711, ECO:0000269|PubMed:26631338, ECO:0000269|PubMed:27586648, ECO:0000269|PubMed:7751854, ECO:0000269|PubMed:7849712, ECO:0000269|PubMed:7881417, ECO:0000269|PubMed:8012359, ECO:0000269|PubMed:8220423, ECO:0000269|PubMed:9066328, ECO:0000269|PubMed:9138151, ECO:0000269|PubMed:9389851, ECO:0000269|PubMed:9450902, ECO:0000269|PubMed:9497245}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Central core disease of muscle (CCD) [MIM:117000]: Autosomal dominant congenital myopathy, but a severe autosomal recessive form also exists. Both clinical and histological variability is observed. Affected individuals typically display hypotonia and proximal muscle weakness in infancy, leading to the delay of motor milestones. The clinical course of the disorder is usually slow or nonprogressive in adulthood, and the severity of the symptoms may vary from normal to significant muscle weakness. Microscopic examination of CCD-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. {ECO:0000269|PubMed:10097181, ECO:0000269|PubMed:11113224, ECO:0000269|PubMed:11709545, ECO:0000269|PubMed:11741831, ECO:0000269|PubMed:12112081, ECO:0000269|PubMed:12136074, ECO:0000269|PubMed:12565913, ECO:0000269|PubMed:12566385, ECO:0000269|PubMed:12937085, ECO:0000269|PubMed:14670767, ECO:0000269|PubMed:14985404, ECO:0000269|PubMed:17204054, ECO:0000269|PubMed:17226826, ECO:0000269|PubMed:18253926, ECO:0000269|PubMed:18312400, ECO:0000269|PubMed:20142353, ECO:0000269|PubMed:21674524, ECO:0000269|PubMed:23558838, ECO:0000269|PubMed:24561095, ECO:0000269|PubMed:26381711, ECO:0000269|PubMed:27234031, ECO:0000269|PubMed:27586648, ECO:0000269|PubMed:7829078, ECO:0000269|PubMed:8220422, ECO:0000269|PubMed:8220423, ECO:0000269|PubMed:9497245}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Multiminicore disease with external ophthalmoplegia (MMDO) [MIM:255320]: Clinically heterogeneous neuromuscular disorder. General features include neonatal hypotonia, delayed motor development, and generalized muscle weakness and amyotrophy, which may progress slowly or remain stable. Muscle biopsy shows multiple, poorly circumscribed, short areas of sarcomere disorganization and mitochondria depletion (areas termed minicores) in most muscle fibers. Typically, no dystrophic signs, such as muscle fiber necrosis or regeneration or significant endomysial fibrosis, are present in multiminicore disease. {ECO:0000269|PubMed:12719381, ECO:0000269|PubMed:16380615, ECO:0000269|PubMed:20583297}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=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.;