Gene: RYR1

Alternate names for this Gene: CCO|MHS|MHS1|PPP1R137|RYDR|RYR|RYR-1|SKRR

Gene Summary: This gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described.

Gene is located in Chromosome: 19

Location in Chromosome : 19q13.2

Description of this Gene: ryanodine receptor 1

Type of Gene: protein-coding

rs200546266 in RYR1 gene and Arthrogryposis PMID 31680123 2020 The genomic and clinical landscape of fetal akinesia.

rs71356805 in RYR1 gene and Blood basophil count (lab test) PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs118192115 in RYR1 gene and Central Core Myopathy (disorder) PMID 21989361 2012 Clinical utility gene card for: Central core disease.

PMID 22009146 2012 Clinical utility gene card for: Multi-minicore disease.

PMID 25747005 2015 A novel large deletion in the RYR1 gene in a Belgian family with late-onset and recessive core myopathy.

PMID 18253926 2008 Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.

PMID 17226826 2007 Central core disease due to recessive mutations in RYR1 gene: is it more common than described?

PMID 23919265 2013 Genotype-phenotype correlations in recessive RYR1-related myopathies.

PMID 16621918 2006 Central core disease is due to RYR1 mutations in more than 90% of patients.

PMID 24561095 2014 Novel RYR1 missense mutations in six Chinese patients with central core disease.

PMID 11709545 2001 Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.

PMID 27586648 2016 Genotype-Phenotype Correlations of Malignant Hyperthermia and Central Core Disease Mutations in the Central Region of the RYR1 Channel.

PMID 27234031 2017 Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population.

PMID 10097181 1999 A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease.

PMID 12136074 2002 Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.

PMID 12112081 2002 A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene.

PMID 12565913 2003 Principal mutation hotspot for central core disease and related myopathies in the C-terminal transmembrane region of the RYR1 gene.

PMID 11113224 2000 A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy.

PMID 26381711 2015 Several Ryanodine Receptor Type 1 Gene Mutations of p.Arg2508 Are Potential Sources of Malignant Hyperthermia.

PMID 8220422 1993 A mutation in the human ryanodine receptor gene associated with central core disease.

PMID 18312400 2008 Novel RYR1 missense mutation causes core rod myopathy.

PMID 20142353 2010 Functional properties of RYR1 mutations identified in Swedish patients with malignant hyperthermia and central core disease.

PMID 21674524 2011 Dominant and recessive RYR1 mutations in adults with core lesions and mild muscle symptoms.

PMID 8220423 1993 Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia.

PMID 17204054 2007 Inheritance of a novel RYR1 mutation in a family with myotonic dystrophy type 1.

PMID 23558838 2013 Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible population of the United States.

PMID 12937085 2003 Dominant and recessive central core disease associated with RYR1 mutations and fetal akinesia.

PMID 9497245 1998 Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.

PMID 7829078 1994 Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel Tyr to Ser mutation in a pedigree with associated central cores.

PMID 20080402 2010 Multi-minicore disease and atypical periodic paralysis associated with novel mutations in the skeletal muscle ryanodine receptor (RYR1) gene.

PMID 22473935 2012 Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.

PMID 25476234 2014 Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.

PMID 24951453 2014 RYR1-related congenital myopathy with fatigable weakness, responding to pyridostigimine.

PMID 27854218 2016 Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases.

rs1248355799 in RYR1 gene and Dysmorphic features PMID 9199552 1997 Malignant-hyperthermia susceptibility is associated with a mutation of the alpha 1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle.

PMID 8661021 1996 The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene.

PMID 23394784 2013 Congenital myopathies--clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom.

PMID 23553484 2013 Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum.

PMID 4149045 1973 Anesthetic-induced malignant hyperpyrexia in children.

PMID 23919265 2013 Genotype-phenotype correlations in recessive RYR1-related myopathies.

PMID 20839240 2010 RYR1 mutations are a common cause of congenital myopathies with central nuclei.

PMID 16163667 2005 Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.

PMID 18765655 2008 King-denborough syndrome caused by a novel mutation in the ryanodine receptor gene.

PMID 16917943 2006 Mutations in RYR1 in malignant hyperthermia and central core disease.

PMID 16380615 2005 Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.

PMID 20583297 2010 Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.

rs200546266 in RYR1 gene and Early severe fetal akinesia sequence PMID 31680123 2020 The genomic and clinical landscape of fetal akinesia.

rs10500279 in RYR1 gene and Left Ventricular Hypertrophy PMID 21828061 2012 Common variants in RYR1 are associated with left ventricular hypertrophy assessed by electrocardiogram.

rs118192140 in RYR1 gene and MINICORE MYOPATHY WITH EXTERNAL OPHTHALMOPLEGIA (disorder) PMID 17483490 2007 Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies.

PMID 22473935 2012 Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.

PMID 26633545 2016 Molecular diagnostic experience of whole-exome sequencing in adult patients.

PMID 22009146 2012 Clinical utility gene card for: Multi-minicore disease.

PMID 21911697 2011 Muscle magnetic resonance imaging in congenital myopathies due to ryanodine receptor type 1 gene mutations.

PMID 20080402 2010 Multi-minicore disease and atypical periodic paralysis associated with novel mutations in the skeletal muscle ryanodine receptor (RYR1) gene.

PMID 12719381 2003 A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia.

PMID 20583297 2010 Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.

PMID 16380615 2005 Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.

rs118192177 in RYR1 gene and Malignant hyperpyrexia due to anesthesia PMID 25558065 2015 Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.

PMID 9497245 1998 Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.

PMID 10484775 1999 Screening of the ryanodine receptor gene in 105 malignant hyperthermia families: novel mutations and concordance with the in vitro contracture test.

PMID 19919814 2010 Mild clinical and histopathological features in patients who carry the frequent and causative malignant hyperthermia RyR1 mutation p.Thr2206Met.

PMID 19648156 2009 Genetic variation in RYR1 and malignant hyperthermia phenotypes.

PMID 23919265 2013 Genotype-phenotype correlations in recessive RYR1-related myopathies.

PMID 12220451 2002 Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 Thr2206Met (C6617T) mutation.

PMID 11575529 2001 North American malignant hyperthermia population: screening of the ryanodine receptor gene and identification of novel mutations.

PMID 12411788 2002 Presence of two different genetic traits in malignant hyperthermia families: implication for genetic analysis, diagnosis, and incidence of malignant hyperthermia susceptibility.

PMID 25957634 2015 Centronuclear myopathies: genotype-phenotype correlation and frequency of defined genetic forms in an Italian cohort.

PMID 25637381 2015 Actionable exomic incidental findings in 6503 participants: challenges of variant classification.

PMID 23558838 2013 Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible population of the United States.

PMID 12208234 2002 Mutations in the RYR1 gene in Italian patients at risk for malignant hyperthermia: evidence for a cluster of novel mutations in the C-terminal region.

PMID 16163667 2005 Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.

PMID 12434264 2002 [Current aspects of the diagnosis of malignant hyperthermia].

PMID 14999498 2004 Adult onset multi/minicore myopathy associated with a mutation in the RYR1 gene.

PMID 18564801 2008 Identification of genetic mutations in Australian malignant hyperthermia families using sequencing of RYR1 hotspots.

PMID 25735680 2015 Analysis of the entire ryanodine receptor type 1 and alpha 1 subunit of the dihydropyridine receptor (CACNA1S) coding regions for variants associated with malignant hyperthermia in Australian families.

PMID 23459219 2013 Skeletal muscle ryanodine receptor mutations associated with malignant hyperthermia showed enhanced intensity and sensitivity to triggering drugs when expressed in human embryonic kidney cells.

PMID 12066726 2002 Malignant hyperthermia associated with exercise-induced rhabdomyolysis or congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian pedigrees.

PMID 24433488 2014 Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study.

PMID 18253926 2008 Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.

PMID 17483490 2007 Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies.

PMID 23553787 2013 RyR1 deficiency in congenital myopathies disrupts excitation-contraction coupling.

PMID 19645060 2009 A RYR1 mutation associated with recessive congenital myopathy and dominant malignant hyperthermia in Asian families.

PMID 22473935 2012 Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.

rs111272095 in RYR1 gene and Malignant hyperthermia susceptibility type 1 PMID 25356965 2015 ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.

PMID 23788249 2013 ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.

PMID 27854360 2017 Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

PMID 14870754 2004 Malignant hyperthermia genetic testing in North America Working Group Meeting. Bethesda, Maryland. September 4-5, 2002.

PMID 15448513 2004 Malignant hyperthermia in North America: genetic screening of the three hot spots in the type I ryanodine receptor gene.

PMID 23558838 2013 Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible population of the United States.

PMID 26115329 2015 Divergent Activity Profiles of Type 1 Ryanodine Receptor Channels Carrying Malignant Hyperthermia and Central Core Disease Mutations in the Amino-Terminal Region.

PMID 7849712 1994 Detection of a novel RYR1 mutation in four malignant hyperthermia pedigrees.

PMID 12208234 2002 Mutations in the RYR1 gene in Italian patients at risk for malignant hyperthermia: evidence for a cluster of novel mutations in the C-terminal region.

PMID 7751854 1995 Ryanodine receptor gene point mutation and malignant hyperthermia susceptibility.

PMID 8012359 1994 Detection of a novel common mutation in the ryanodine receptor gene in malignant hyperthermia: implications for diagnosis and heterogeneity studies.

PMID 9450902 1998 Novel mutations at a CpG dinucleotide in the ryanodine receptor in malignant hyperthermia.

PMID 9066328 1997 Identification of heterozygous and homozygous individuals with the novel RYR1 mutation Cys35Arg in a large kindred.

PMID 26381711 2015 Several Ryanodine Receptor Type 1 Gene Mutations of p.Arg2508 Are Potential Sources of Malignant Hyperthermia.

PMID 11389482 2001 Single-amino-acid deletion in the RYR1 gene, associated with malignant hyperthermia susceptibility and unusual contraction phenotype.

PMID 12059893 2002 Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients susceptible to malignant hyperthermia who show definite IVCT results: identification of three novel mutations.

PMID 8220423 1993 Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia.

PMID 11928716 2002 Novel mutations in C-terminal channel region of the ryanodine receptor in malignant hyperthermia patients.

PMID 20681998 2011 Novel missense mutations and unexpected multiple changes of RYR1 gene in 75 malignant hyperthermia families.

PMID 1774074 1991 A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia.

PMID 11525881 2001 Identification and functional characterization of a novel ryanodine receptor mutation causing malignant hyperthermia in North American and South American families.

PMID 14985404 2004 RYR1 mutations in UK central core disease patients: more than just the C-terminal transmembrane region of the RYR1 gene.

PMID 12123492 2002 Novel skeletal muscle ryanodine receptor mutation in a large Brazilian family with malignant hyperthermia.

PMID 11575529 2001 North American malignant hyperthermia population: screening of the ryanodine receptor gene and identification of novel mutations.

PMID 28687594 2017 Reduced threshold for store overload-induced Ca2+ release is a common defect of RyR1 mutations associated with malignant hyperthermia and central core disease.

PMID 12411788 2002 Presence of two different genetic traits in malignant hyperthermia families: implication for genetic analysis, diagnosis, and incidence of malignant hyperthermia susceptibility.

rs1555801872 in RYR1 gene and Movement Disorders PMID 16917943 2006 Mutations in RYR1 in malignant hyperthermia and central core disease.

PMID 20583297 2010 Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.

PMID 8661021 1996 The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene.

PMID 16380615 2005 Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.

PMID 18765655 2008 King-denborough syndrome caused by a novel mutation in the ryanodine receptor gene.

PMID 9199552 1997 Malignant-hyperthermia susceptibility is associated with a mutation of the alpha 1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle.

PMID 20839240 2010 RYR1 mutations are a common cause of congenital myopathies with central nuclei.

PMID 23553484 2013 Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum.

PMID 23919265 2013 Genotype-phenotype correlations in recessive RYR1-related myopathies.

PMID 4149045 1973 Anesthetic-induced malignant hyperpyrexia in children.

PMID 16163667 2005 Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.

PMID 23394784 2013 Congenital myopathies--clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom.

rs1248355799 in RYR1 gene and Muscle hypotonia PMID 23553484 2013 Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum.

PMID 23394784 2013 Congenital myopathies--clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom.

PMID 20839240 2010 RYR1 mutations are a common cause of congenital myopathies with central nuclei.

PMID 16163667 2005 Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.

PMID 16380615 2005 Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.

PMID 4149045 1973 Anesthetic-induced malignant hyperpyrexia in children.

PMID 23919265 2013 Genotype-phenotype correlations in recessive RYR1-related myopathies.

PMID 16917943 2006 Mutations in RYR1 in malignant hyperthermia and central core disease.

PMID 20583297 2010 Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.

PMID 18765655 2008 King-denborough syndrome caused by a novel mutation in the ryanodine receptor gene.

PMID 9199552 1997 Malignant-hyperthermia susceptibility is associated with a mutation of the alpha 1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle.

PMID 8661021 1996 The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene.

rs193922839 in RYR1 gene and Neuromuscular Diseases PMID 17483490 2007 Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies.

PMID 19645060 2009 A RYR1 mutation associated with recessive congenital myopathy and dominant malignant hyperthermia in Asian families.

PMID 22473935 2012 Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.

PMID 23553787 2013 RyR1 deficiency in congenital myopathies disrupts excitation-contraction coupling.

PMID 18253926 2008 Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.

PMID 25637381 2015 Actionable exomic incidental findings in 6503 participants: challenges of variant classification.

PMID 24627108 2014 Whole-exome sequencing in patients with inherited neuropathies: outcome and challenges.

PMID 20839240 2010 RYR1 mutations are a common cause of congenital myopathies with central nuclei.

PMID 21062345 2011 Recessive RYR1 mutations cause unusual congenital myopathy with prominent nuclear internalization and large areas of myofibrillar disorganization.

PMID 24195946 2013 Using exome data to identify malignant hyperthermia susceptibility mutations.

PMID 21455645 2011 Ryanodine receptor type 1 gene mutations found in the Canadian malignant hyperthermia population.

PMID 20080402 2010 Multi-minicore disease and atypical periodic paralysis associated with novel mutations in the skeletal muscle ryanodine receptor (RYR1) gene.

PMID 25476234 2014 Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.

PMID 24951453 2014 RYR1-related congenital myopathy with fatigable weakness, responding to pyridostigimine.

rs1555762532 in RYR1 gene and Rhabdomyolysis PMID 28779239 2017 Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases.