Menu
GeneBe

RYR1

ryanodine receptor 1, the group of Ryanodine receptors|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 19:38433690-38595273

Previous symbols: [ "MHS", "MHS1", "CCO" ]

Links

ENSG00000196218 ∙ NCBI:6261 ∙ OMIM:180901 ∙ HGNC:10483 ∙ Uniprot:P21817 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed

Phenotypes

GenCC

Source: genCC

  • congenital multicore myopathy with external ophthalmoplegia (Definitive), mode of inheritance: AR
  • central core myopathy (Strong), mode of inheritance: AD
  • malignant hyperthermia, susceptibility to, 1 (Strong), mode of inheritance: AD
  • central core myopathy (Strong), mode of inheritance: AR
  • congenital multicore myopathy with external ophthalmoplegia (Strong), mode of inheritance: AR
  • central core myopathy (Supportive), mode of inheritance: AD
  • malignant hyperthermia of anesthesia (Supportive), mode of inheritance: AD
  • lethal multiple pterygium syndrome (Supportive), mode of inheritance: AR
  • King-Denborough syndrome (Supportive), mode of inheritance: AD
  • autosomal recessive centronuclear myopathy (Supportive), mode of inheritance: AR
  • benign Samaritan congenital myopathy (Supportive), mode of inheritance: AR
  • congenital myopathy with myasthenic-like onset (Supportive), mode of inheritance: AR
  • malignant hyperthermia, susceptibility to, 1 (Definitive), mode of inheritance: AD
  • malignant hyperthermia, susceptibility to, 1 (Definitive), mode of inheritance: AD
  • RYR1-related myopathy (Definitive), mode of inheritance: AR
  • RYR1-related myopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Malignant hyperthermia, susceptibility 1; King-Denborough syndrome; Congenital myopathy 1A, autosomal dominant, with susceptibility to malignant hyperthermia; Congenital myopathy 1B, autosomal recessive; Centronuclear myopathyAD/ARCardiovascular; Musculoskeletal; Renal; PharmacogenomicIndividuals with recessive inheritance have been described; Invididuals are susceptible to malignant hyperthermic crisis (which can affect both skeletal muscle and cardiac function) in a number of situations, including when exposed to specific agents such as certain agents used in anesthesia (eg, halothane) or depolarizing muscle relaxants (eg, succinyl choline), and to treat or prevent acute crises, dantrolene can be effective; Individuals may also suffer from exertional rhabdomyolysis or have attacks triggered by tachycardia or acidosis, and precautions may be beneficial; For Minicore myopathy with external ophthalmoplegia, Centronuclear myopathy, individuals with these conditions may also be at risk of malignant hyperthermia, and appropriate precautions may be beneficialCardiovascular; Craniofacial; Musculoskeletal; Renal13396066; 637752; 7362206; 7299413; 6348539; 1774074; 8220423; 8220422; 9199552; 9497245; 10097181; 11113224; 11389482; 11448278; 12112081; 12136074; 12467748; 12719381; 14732627; 16380615; 16163667; 16084090; 17190947; 17376685; 17538032; 18253926; 18765655; 19303294; 19734047; 19807743; 20301565; 20301325; 20839240
Individuals with RYR1-related conditions may be at risk of malignant hyperthermia

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RYR1 gene.

  • RYR1-Related Disorders (4439 variants)
  • not provided (2641 variants)
  • Malignant hyperthermia, susceptibility to, 1 (703 variants)
  • Central core myopathy (616 variants)
  • not specified (533 variants)
  • Congenital multicore myopathy with external ophthalmoplegia (472 variants)
  • Neuromuscular disease, congenital, with uniform type 1 fiber (320 variants)
  • Malignant hyperthermia of anesthesia (210 variants)
  • Inborn genetic diseases (105 variants)
  • Multiminicore myopathy (62 variants)
  • Congenital myopathy with fiber type disproportion (43 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1;King Denborough syndrome;Congenital myopathy with fiber type disproportion;Central core myopathy (42 variants)
  • King Denborough syndrome (39 variants)
  • sevoflurane response - Toxicity (34 variants)
  • enflurane response - Toxicity (34 variants)
  • isoflurane response - Toxicity (34 variants)
  • succinylcholine response - Toxicity (34 variants)
  • halothane response - Toxicity (34 variants)
  • desflurane response - Toxicity (34 variants)
  • methoxyflurane response - Toxicity (34 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome (33 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome;Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion (32 variants)
  • King Denborough syndrome;Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion (28 variants)
  • Malignant hyperthermia, susceptibility to, 1;King Denborough syndrome;Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion (24 variants)
  • RYR1-related myopathy (24 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome;Central core myopathy;Congenital myopathy with fiber type disproportion (23 variants)
  • Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1;King Denborough syndrome;Congenital myopathy with fiber type disproportion (23 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;Central core myopathy;King Denborough syndrome (22 variants)
  • Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;King Denborough syndrome (20 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;King Denborough syndrome (19 variants)
  • King Denborough syndrome;Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;Congenital multicore myopathy with external ophthalmoplegia (19 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;Central core myopathy;King Denborough syndrome;Congenital multicore myopathy with external ophthalmoplegia (16 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome;Congenital myopathy with fiber type disproportion;Malignant hyperthermia, susceptibility to, 1;Central core myopathy (16 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;King Denborough syndrome (16 variants)
  • Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome (15 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;Central core myopathy;Malignant hyperthermia, susceptibility to, 1;King Denborough syndrome (14 variants)
  • Malignant hyperthermia, susceptibility to, 1;King Denborough syndrome;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;Central core myopathy (14 variants)
  • Malignant hypothermia (14 variants)
  • Central core myopathy;King Denborough syndrome;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;Malignant hyperthermia, susceptibility to, 1 (13 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;Congenital myopathy with fiber type disproportion;King Denborough syndrome (12 variants)
  • Congenital myopathy with fiber type disproportion;King Denborough syndrome;Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1 (11 variants)
  • Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (10 variants)
  • Myopathy (10 variants)
  • Congenital myopathy with fiber type disproportion;Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome;Malignant hyperthermia, susceptibility to, 1 (9 variants)
  • See cases (9 variants)
  • Abnormality of the musculature (8 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;King Denborough syndrome;Central core myopathy (8 variants)
  • Congenital myopathy (8 variants)
  • Congenital myopathy with fiber type disproportion;Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome (8 variants)
  • RYR1-Related Disorder (5 variants)
  • Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia (4 variants)
  • Myopathy, RYR1-associated (4 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1;King Denborough syndrome;Central core myopathy;Congenital myopathy with fiber type disproportion (4 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;King Denborough syndrome;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion (4 variants)
  • Central core myopathy;Congenital myopathy with fiber type disproportion;King Denborough syndrome;Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia (4 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;King Denborough syndrome;Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia (4 variants)
  • King Denborough syndrome;Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion (4 variants)
  • Central core disease, autosomal recessive (4 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome;Central core myopathy;Congenital myopathy with fiber type disproportion;Malignant hyperthermia, susceptibility to, 1 (4 variants)
  • Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion (4 variants)
  • Malignant hyperthermia, susceptibility to, 1;Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;King Denborough syndrome (4 variants)
  • Congenital myopathy with fiber type disproportion;Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome;Central core myopathy;Malignant hyperthermia, susceptibility to, 1 (3 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia (3 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;Malignant hyperthermia, susceptibility to, 1;King Denborough syndrome;Central core myopathy (3 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion (3 variants)
  • King Denborough syndrome;Malignant hyperthermia, susceptibility to, 1;Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion (3 variants)
  • Malignant hyperthermia, susceptibility to, 1;King Denborough syndrome;Central core myopathy;Congenital myopathy with fiber type disproportion;Congenital multicore myopathy with external ophthalmoplegia (2 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome;Central core myopathy (2 variants)
  • 10 conditions (2 variants)
  • Elevated circulating creatine kinase concentration;Myalgia;Exercise-induced myalgia (2 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;Malignant hyperthermia, susceptibility to, 1 (2 variants)
  • Distal arthrogryposis (2 variants)
  • Malignant hyperthermia and exertional rhabdomyolosis (2 variants)
  • Arthrogryposis multiplex congenita (2 variants)
  • Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion (2 variants)
  • Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;King Denborough syndrome (2 variants)
  • Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion (2 variants)
  • King Denborough syndrome;Congenital myopathy with fiber type disproportion;Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;Malignant hyperthermia, susceptibility to, 1 (2 variants)
  • Ullrich congenital muscular dystrophy 1 (2 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;King Denborough syndrome;Congenital myopathy with fiber type disproportion (2 variants)
  • Malignant hyperthermia, susceptibility to, 1;Central core myopathy (2 variants)
  • Congenital myasthenic syndrome (2 variants)
  • King Denborough syndrome;Central core myopathy;Congenital myopathy with fiber type disproportion;Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1 (2 variants)
  • Centronuclear myopathy (2 variants)
  • Neuromuscular disease (2 variants)
  • Axial myopathy, late-onset (2 variants)
  • Hydrops fetalis (2 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;King Denborough syndrome;Congenital myopathy with fiber type disproportion;Malignant hyperthermia, susceptibility to, 1 (2 variants)
  • EMG: myopathic abnormalities;Congenital hip dislocation;Congenital muscular dystrophy;Generalized muscle weakness (1 variants)
  • Scoliosis;Pelvic girdle muscle weakness;Delayed gross motor development;Proximal muscle weakness;Progressive distal muscle weakness (1 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;Central core myopathy;Malignant hyperthermia, susceptibility to, 1 (1 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;King Denborough syndrome;Central core myopathy;Malignant hyperthermia, susceptibility to, 1 (1 variants)
  • King Denborough syndrome;Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy (1 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;Central core myopathy;King Denborough syndrome;Malignant hyperthermia, susceptibility to, 1 (1 variants)
  • Congenital muscular dystrophy;Myopathy;Respiratory insufficiency (1 variants)
  • Neuromuscular disease;Malignant hyperthermia of anesthesia (1 variants)
  • Congenital myopathy with fiber type disproportion;Central core myopathy;King Denborough syndrome;Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia (1 variants)
  • Fetal akinesia deformation sequence 1;Arthrogryposis multiplex congenita (1 variants)
  • Multiminicore myopathy;Centronuclear myopathy;Congenital myopathy with fiber type disproportion;Malignant hyperthermia, susceptibility to, 1 (1 variants)
  • - (1 variants)
  • Congenital myopathy with fiber type disproportion;Central core myopathy;Malignant hyperthermia, susceptibility to, 1;King Denborough syndrome;Congenital multicore myopathy with external ophthalmoplegia (1 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;King Denborough syndrome;Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy (1 variants)
  • Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1 (1 variants)
  • Lower limb amyotrophy;Clubfoot;EMG abnormality (1 variants)
  • Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;Multiminicore myopathy;Myopathy, RYR1-associated (1 variants)
  • Congenital contracture;Short stature;Delayed gross motor development;Proximal amyotrophy (1 variants)
  • Mildly elevated creatine kinase;Limb pain;Osteoporosis;Myotonia (1 variants)
  • Malignant hyperthermia, susceptibility to, 1;Central core myopathy;King Denborough syndrome;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion (1 variants)
  • Absence of the sacrum;Ptosis;History of neonatal hypotonia (1 variants)
  • Respiratory insufficiency;Congenital muscular dystrophy;Myopathy (1 variants)
  • Rhabdomyolysis (1 variants)
  • Malignant hyperthermia equivocal with halotane (1 variants)
  • Congenital myopathy with cores (1 variants)
  • Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;Congenital multicore myopathy with external ophthalmoplegia (1 variants)
  • Congenital myopathy with fiber type disproportion;Central core myopathy;Myopathy, RYR1-associated;Malignant hyperthermia, susceptibility to, 1;Multiminicore myopathy (1 variants)
  • Myalgia;Elevated circulating creatine kinase concentration;Exercise-induced myalgia (1 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;Congenital myopathy with fiber type disproportion (1 variants)
  • Congenital myopathy with fiber type disproportion;Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1 (1 variants)
  • Congenital myasthenic syndrome 12 (1 variants)
  • Muscle weakness (1 variants)
  • Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;King Denborough syndrome;Central core myopathy (1 variants)
  • Central core myopathy;Malignant hyperthermia, susceptibility to, 1;King Denborough syndrome;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion (1 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy (1 variants)
  • Multi-minicore disease and atypical periodic paralysis (1 variants)
  • Central core myopathy;King Denborough syndrome;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion;Congenital multicore myopathy with external ophthalmoplegia (1 variants)
  • Multiminicore/minicore/multicore disease (1 variants)
  • Generalized muscle weakness;EMG: myopathic abnormalities;Congenital hip dislocation;Congenital muscular dystrophy (1 variants)
  • Myopathy, progressive axial with cataracts (1 variants)
  • Muscular dystrophy and arthrogryposis (1 variants)
  • Pelvic girdle muscle weakness;Scoliosis;Progressive distal muscle weakness;Proximal muscle weakness;Delayed gross motor development (1 variants)
  • King Denborough syndrome;Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;Malignant hyperthermia, susceptibility to, 1;Congenital myopathy with fiber type disproportion (1 variants)
  • Hypotonia (1 variants)
  • Central core myopathy;Congenital myopathy with fiber type disproportion;Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia (1 variants)
  • Congenital multicore myopathy with external ophthalmoplegia;Malignant hyperthermia, susceptibility to, 1;Central core myopathy;Congenital myopathy with fiber type disproportion (1 variants)
  • Congenital myopathy with fiber type disproportion;Congenital multicore myopathy with external ophthalmoplegia;Central core myopathy;Malignant hyperthermia, susceptibility to, 1 (1 variants)
  • Central core myopathy;Neuromuscular disease (1 variants)
  • 12 conditions (1 variants)
  • Central core myopathy;King Denborough syndrome;Malignant hyperthermia, susceptibility to, 1;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RYR1 gene is commonly pathogenic or not.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous 1 1 50 1324 38 1414
missense 53 186 2349 139 22 2749
nonsense 75 21 5 101
start loss 0
frameshift 94 51 4 2 151
inframe indel 4 3 85 4 1 97
splice variant 21 74 129 214 13 451
non coding 1 1 34 645 249 930
Total 249 337 2656 2328 323

Highest pathogenic variant AF is 0.0000657

Variants in RYR1

This is a list of pathogenic ClinVar variants found in the RYR1 region.

Position Type Phenotype Significance ClinVar
19-38433712-G-A Central core myopathy • Congenital multicore myopathy with external ophthalmoplegia • Malignant hyperthermia, susceptibility to, 1 Uncertain significance (Jan 13, 2018)link
19-38433722-T-C Central core myopathy • Congenital multicore myopathy with external ophthalmoplegia • Malignant hyperthermia, susceptibility to, 1 • Neuromuscular disease, congenital, with uniform type 1 fiber Benign (Jun 28, 2018)link
19-38433728-C-T Central core myopathy • Neuromuscular disease, congenital, with uniform type 1 fiber • Malignant hyperthermia, susceptibility to, 1 • Congenital multicore myopathy with external ophthalmoplegia Benign/Likely benign (Jan 13, 2018)link
19-38433741-CCCCAGCCCGCCCCCAGCCCTCCCG-C Likely benign (Feb 11, 2019)link
19-38433746-G-GC Malignant hyperthermia of anesthesia • Neuromuscular disease, congenital, with uniform type 1 fiber • Central core myopathy • Multiminicore myopathy Uncertain significance (Jun 14, 2016)link
19-38433756-A-C Central core myopathy • Congenital multicore myopathy with external ophthalmoplegia • Malignant hyperthermia, susceptibility to, 1 • Neuromuscular disease, congenital, with uniform type 1 fiber • Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;King Denborough syndrome;Malignant hyperthermia, susceptibility to, 1 Uncertain significance (Dec 14, 2021)link
19-38433757-G-GC Malignant hyperthermia of anesthesia • Multiminicore myopathy • Central core myopathy • Neuromuscular disease, congenital, with uniform type 1 fiber Uncertain significance (Jun 14, 2016)link
19-38433761-T-C Malignant hyperthermia, susceptibility to, 1 • Central core myopathy • Congenital multicore myopathy with external ophthalmoplegia Uncertain significance (Jan 13, 2018)link
19-38433761-T-G Neuromuscular disease, congenital, with uniform type 1 fiber • Malignant hyperthermia, susceptibility to, 1 • Central core myopathy • Congenital multicore myopathy with external ophthalmoplegia • Central core myopathy;Congenital multicore myopathy with external ophthalmoplegia;Congenital myopathy with fiber type disproportion;King Denborough syndrome;Malignant hyperthermia, susceptibility to, 1 Uncertain significance (Aug 16, 2021)link
19-38433765-G-C Congenital multicore myopathy with external ophthalmoplegia • Central core myopathy • Malignant hyperthermia, susceptibility to, 1 Uncertain significance (Jan 12, 2018)link
19-38433769-A-C Congenital multicore myopathy with external ophthalmoplegia • Central core myopathy • Malignant hyperthermia, susceptibility to, 1 Uncertain significance (Jan 12, 2018)link
19-38433793-C-G not specified Likely benign (-)link
19-38433799-C-T Congenital multicore myopathy with external ophthalmoplegia • Malignant hyperthermia, susceptibility to, 1 Uncertain significance (Jan 13, 2018)link
19-38433832-G-C Uncertain significance (Aug 02, 2022)link
19-38433834-G-C Neuromuscular disease, congenital, with uniform type 1 fiber • Malignant hyperthermia, susceptibility to, 1 • Congenital multicore myopathy with external ophthalmoplegia • Central core myopathy Uncertain significance (Jan 13, 2018)link
19-38433850-A-G RYR1-Related Disorders Likely benign (Aug 22, 2022)link
19-38433850-A-AGAC RYR1-Related Disorders Uncertain significance (Jul 06, 2022)link
19-38433853-C-A Uncertain significance (May 03, 2021)link
19-38433862-G-A Likely benign (Jul 18, 2018)link
19-38433864-TCC-CG not provided (-)link
19-38433867-T-G Malignant hyperthermia, susceptibility to, 1 • RYR1-Related Disorders Likely pathogenic (Apr 07, 2023)link
19-38433869-C-A RYR1-Related Disorders Likely benign (Jun 01, 2018)link
19-38433869-C-T Uncertain significance (May 07, 2021)link
19-38433871-G-C RYR1-Related Disorders Likely benign (Feb 05, 2021)link
19-38433874-G-A RYR1-Related Disorders Uncertain significance (Jul 28, 2022)link

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RYR1protein_codingprotein_codingENST00000359596 106153866
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.59e-291.0012540403441257480.00137
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.9226982.99e+30.9010.00021832806
Missense in Polyphen524603.910.867686389
Synonymous-2.1713651.27e+31.080.00009729980
Loss of Function9.05972520.3850.00001392847

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002360.00234
Ashkenazi Jewish0.004280.00428
East Asian0.0008810.000870
Finnish0.001070.00106
European (Non-Finnish)0.001580.00156
Middle Eastern0.0008810.000870
South Asian0.0003930.000392
Other0.001640.00163

dbNSFP

Source: dbNSFP

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.;
Pathway
Oxytocin signaling pathway - Homo sapiens (human);Long-term depression - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Myometrial Relaxation and Contraction Pathways;Cell-type Dependent Selectivity of CCK2R Signaling;Calcium Regulation in the Cardiac Cell;Stimuli-sensing channels;Ion channel transport;Ion homeostasis;Transport of small molecules;Cardiac conduction;Muscle contraction (Consensus)

Intolerance Scores

loftool
0.00248
rvis_EVS
-8.29
rvis_percentile_EVS
0.01

Haploinsufficiency Scores

pHI
0.222
hipred
Y
hipred_score
0.637
ghis
0.539

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.872

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Ryr1
Phenotype
muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); digestive/alimentary phenotype; limbs/digits/tail phenotype; skeleton phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Zebrafish Information Network

Gene name
ryr1b
Affected structure
fast muscle cell
Phenotype tag
abnormal
Phenotype quality
disorganized

Gene ontology

Biological process
response to hypoxia;outflow tract morphogenesis;calcium ion transport;muscle contraction;release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;response to caffeine;ion transmembrane transport;skin development;ossification involved in bone maturation;skeletal muscle fiber development;release of sequestered calcium ion into cytosol;protein homotetramerization;regulation of cytosolic calcium ion concentration;cellular response to calcium ion;cellular response to caffeine;regulation of cardiac conduction
Cellular component
cytoplasm;smooth endoplasmic reticulum;plasma membrane;integral component of plasma membrane;cell cortex;junctional sarcoplasmic reticulum membrane;terminal cisterna;sarcoplasmic reticulum;Z disc;junctional membrane complex;T-tubule;cytoplasmic vesicle membrane;integral component of organelle membrane;I band;sarcoplasmic reticulum membrane;calcium channel complex;sarcolemma;extracellular exosome;ryanodine receptor complex
Molecular function
protease binding;ryanodine-sensitive calcium-release channel activity;voltage-gated calcium channel activity;calcium channel activity;calcium ion binding;protein binding;calmodulin binding;ATP binding;calcium-release channel activity;calcium-induced calcium release activity