Gene: RYR2

Alternate names for this Gene: ARVC2|ARVD2|RYR-2|RyR|VTSIP

Gene Summary: This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia.

Gene is located in Chromosome: 1

Location in Chromosome : 1q43

Description of this Gene: ryanodine receptor 2

Type of Gene: protein-coding

rs121918601 in RYR2 gene and ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 2 PMID 11159936 2001 Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2).

rs2797436 in RYR2 gene and Adolescent idiopathic scoliosis PMID 30019117 2018 The coexistence of copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) at a locus can result in distorted calculations of the significance in associating SNPs to disease.

rs794728708 in RYR2 gene and Catecholaminergic Polymorphic Ventricular Tachycardia Type 1 PMID 19926015 2009 The RYR2-encoded ryanodine receptor/calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long QT syndrome: a comprehensive open reading frame mutational analysis.

PMID 24136861 2014 Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia.

PMID 18752142 2008 Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers.

PMID 21454795 2011 Inherited dysfunction of sarcoplasmic reticulum Ca2+ handling and arrhythmogenesis.

PMID 16188589 2005 Spectrum and prevalence of cardiac ryanodine receptor (RyR2) mutations in a cohort of unrelated patients referred explicitly for long QT syndrome genetic testing.

PMID 24025405 2013 New exome data question the pathogenicity of genetic variants previously associated with catecholaminergic polymorphic ventricular tachycardia.

PMID 20106799 2010 High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening.

PMID 14571276 2003 Molecular genetics of exercise-induced polymorphic ventricular tachycardia: identification of three novel cardiac ryanodine receptor mutations and two common calsequestrin 2 amino-acid polymorphisms.

PMID 27231019 2016 Implantable Loop Recorder Monitoring for Refining Management of Children With Inherited Arrhythmia Syndromes.

PMID 15721128 2005 Unusual clinical presentation in a family with catecholaminergic polymorphic ventricular tachycardia due to a G14876A ryanodine receptor gene mutation.

PMID 28237968 2017 Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations.

rs200236750 in RYR2 gene and Death in infancy PMID 27435932 2016 Postmortem genetic screening for the identification, verification, and reporting of genetic variants contributing to the sudden death of the young.

rs3766889 in RYR2 gene and Forced expiratory volume function PMID 30061609 2018 Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.

rs10495399 in RYR2 gene and Low density lipoprotein cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs2485570 in RYR2 gene and Narcolepsy PMID 19629137 2009 Genome-wide association database developed in the Japanese Integrated Database Project.

rs2819742 in RYR2 gene and Rhabdomyolysis PMID 21386754 2011 Cerivastatin, genetic variants, and the risk of rhabdomyolysis.

rs2797436 in RYR2 gene and SCOLIOSIS, ISOLATED, SUSCEPTIBILITY TO, 3 PMID 30019117 2018 The coexistence of copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) at a locus can result in distorted calculations of the significance in associating SNPs to disease.

rs863223354 in RYR2 gene and Schizophrenia, Childhood PMID 26508570 2016 De novo variants in sporadic cases of childhood onset schizophrenia.

rs10495399 in RYR2 gene and Serum LDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs16835265 in RYR2 gene and Serum total cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 24386095 2013 A genome wide association study identifies common variants associated with lipid levels in the Chinese population.

rs200918659 in RYR2 gene and Triglycerides measurement PMID 30576415 2019 Very low-depth whole-genome sequencing in complex trait association studies.

PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 24386095 2013 A genome wide association study identifies common variants associated with lipid levels in the Chinese population.

rs1060500142 in RYR2 gene and VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 1 (disorder) PMID 16084945 2005 Juvenile sudden death in a family with polymorphic ventricular arrhythmias caused by a novel RyR2 gene mutation: evidence of specific morphological substrates.

PMID 22374134 2012 Abnormal termination of Ca2+ release is a common defect of RyR2 mutations associated with cardiomyopathies.

PMID 19913485 2009 Crystal structures of the N-terminal domains of cardiac and skeletal muscle ryanodine receptors: insights into disease mutations.

PMID 16188589 2005 Spectrum and prevalence of cardiac ryanodine receptor (RyR2) mutations in a cohort of unrelated patients referred explicitly for long QT syndrome genetic testing.

PMID 17984046 2007 Loss of luminal Ca2+ activation in the cardiac ryanodine receptor is associated with ventricular fibrillation and sudden death.

PMID 12106942 2002 Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death: early diagnosis of asymptomatic carriers.

PMID 15466642 2004 Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes.

PMID 15046073 2004 Gene symbol: RYR2. Disease: Effort-induced polymorphic ventricular arrhythmias.

PMID 14571276 2003 Molecular genetics of exercise-induced polymorphic ventricular tachycardia: identification of three novel cardiac ryanodine receptor mutations and two common calsequestrin 2 amino-acid polymorphisms.

PMID 24793461 2014 A novel RyR2 mutation in a 2-year-old baby presenting with atrial fibrillation, atrial flutter, and atrial ectopic tachycardia.

PMID 27733687 2016 Enhanced Cytosolic Ca2+ Activation Underlies a Common Defect of Central Domain Cardiac Ryanodine Receptor Mutations Linked to Arrhythmias.

PMID 25372681 2014 Structural insights into the human RyR2 N-terminal region involved in cardiac arrhythmias.

PMID 12093772 2002 Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia.

PMID 15544015 2004 Targeted mutational analysis of the RyR2-encoded cardiac ryanodine receptor in sudden unexplained death: a molecular autopsy of 49 medical examiner/coroner's cases.

PMID 11208676 2001 Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia.

PMID 15046072 2004 Gene symbol: RYR2. Disease: Effort-induced polymorphic ventricular arrhythmias.

PMID 11157710 2001 Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia.

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 25356965 2015 ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.

PMID 21810866 2011 HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA).

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

PMID 23994779 2013 Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.

PMID 16239587 2005 Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death.

PMID 15364606 2004 Mutant cardiac ryanodine receptors and ventricular arrhythmias: is 'gain-of-function' obligatory?

PMID 22828895 2012 Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia.

PMID 22221940 2012 Follow-up with exercise test of effort-induced ventricular arrhythmias linked to ryanodine receptor type 2 gene mutations.

PMID 15364613 2004 Functional heterogeneity of ryanodine receptor mutations associated with sudden cardiac death.

PMID 11159936 2001 Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2).

PMID 19926015 2009 The RYR2-encoded ryanodine receptor/calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long QT syndrome: a comprehensive open reading frame mutational analysis.

PMID 20676041 2011 A novel CPVT mutation, E189D, was identified.

PMID 25087098 2014 Hypertrophy of lymphoid organs is a possible phenotypic characteristic of R420W mutation of the cardiac ryanodine receptor gene: a study using a knock-in mouse model.

PMID 22787013 2012 Familial evaluation in catecholaminergic polymorphic ventricular tachycardia: disease penetrance and expression in cardiac ryanodine receptor mutation-carrying relatives.

PMID 17062961 2006 Postmortem molecular screening for cardiac ryanodine receptor type 2 mutations in sudden unexplained death: R420W mutated case with characteristics of status thymico-lymphatics.

PMID 26153920 2015 Functional abnormalities in iPSC-derived cardiomyocytes generated from CPVT1 and CPVT2 patients carrying ryanodine or calsequestrin mutations.

PMID 28449774 2017 Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.

PMID 24025405 2013 New exome data question the pathogenicity of genetic variants previously associated with catecholaminergic polymorphic ventricular tachycardia.

PMID 28422759 2017 RyR2R420Q catecholaminergic polymorphic ventricular tachycardia mutation induces bradycardia by disturbing the coupled clock pacemaker mechanism.

PMID 23871484 2013 The cardiac ryanodine receptor N-terminal region contains an anion binding site that is targeted by disease mutations.

PMID 25193700 2014 A knock-in mouse model of N-terminal R420W mutation of cardiac ryanodine receptor exhibits arrhythmogenesis with abnormal calcium dynamics in cardiomyocytes.

PMID 21616285 2011 Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia.

PMID 22373669 2012 Mortality of inherited arrhythmia syndromes: insight into their natural history.

PMID 25440180 2015 Non-ventricular, Clinical, and Functional Features of the RyR2(R420Q) Mutation Causing Catecholaminergic Polymorphic Ventricular Tachycardia.

PMID 20961976 2010 Ryanodine receptors: structure, expression, molecular details, and function in calcium release.

PMID 23595086 2013 Genetic background of catecholaminergic polymorphic ventricular tachycardia in Japan.

PMID 16517285 2006 A novel mutation (Arg169Gln) of the cardiac ryanodine receptor gene causing exercise-induced bidirectional ventricular tachycardia.

PMID 19541610 2009 "Crystal structure of type I ryanodine receptor amino-terminal beta-trefoil domain reveals a disease-associated mutation ""hot spot"" loop."

PMID 16873551 2006 Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy.

PMID 20106799 2010 High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening.

PMID 24136861 2014 Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia.

PMID 21454795 2011 Inherited dysfunction of sarcoplasmic reticulum Ca2+ handling and arrhythmogenesis.

PMID 27482086 2016 Leaky RyR2 channels unleash a brainstem spreading depolarization mechanism of sudden cardiac death.

PMID 20157052 2010 Accelerated development of pressure overload-induced cardiac hypertrophy and dysfunction in an RyR2-R176Q knockin mouse model.

PMID 18752142 2008 Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers.

PMID 14571276 2003 We screened 12 Finnish CPVT probands for mutations in these genes and identified three novel RYR2 mutations (V2306I, P4902L, R4959Q), which were absent in unaffected and control individuals.

PMID 15131021 2004 Denaturing HPLC-based approach for detecting RYR2 mutations involved in malignant arrhythmias.

PMID 19398665 2009 Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia.

PMID 28600387 2017 Genetic Testing in the Evaluation of Unexplained Cardiac Arrest: From the CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry).

PMID 16391617 2006 Mechanisms of Disease: ryanodine receptor defects in heart failure and fatal arrhythmia.

PMID 28237968 2017 Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations.

PMID 20851825 2011 We identified a heterozygous p.Arg2401His mutation of RYR2 by sequencing the DNA of a 7-year-old girl who was referred for catecholaminergic polymorphic ventricular tachycardia (CPVT).

PMID 15749201 2005 Since FKBP12.6 plays a critical role in Ca channel gating, the R2401H mutation can be expected to alter Ca-induced Ca release and E-C coupling resulting in CPVT.

PMID 21292648 2011 Successful treatment of catecholaminergic polymorphic ventricular tachycardia with flecainide: a case report and review of the current literature.

PMID 26114861 2015 Gender Differences in the Inheritance Mode of RYR2 Mutations in Catecholaminergic Polymorphic Ventricular Tachycardia Patients.

PMID 14571276 2003 We screened 12 Finnish CPVT probands for mutations in these genes and identified three novel RYR2 mutations (V2306I, P4902L, R4959Q), which were absent in unaffected and control individuals.

PMID 15721128 2005 Unusual clinical presentation in a family with catecholaminergic polymorphic ventricular tachycardia due to a G14876A ryanodine receptor gene mutation.

rs3766889 in RYR2 gene and Vital capacity PMID 30061609 2018 Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.