RYR2

Summary

Gene Symbol: RYR2
Description: ryanodine receptor 2
Alias: ARVC2, ARVD2, RYR-2, RyR, VTSIP, ryanodine receptor 2, cardiac muscle ryanodine receptor-calcium release channel, cardiac-type ryanodine receptor, islet-type ryanodine receptor, kidney-type ryanodine receptor, ryanodine receptor 2 (cardiac), type 2 ryanodine receptor
Species: human
Products:     RYR2

Top Publications

  1. Marx S, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, et al. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell. 2000;101:365-76 pubmed
    ..The channel is a tetramer comprised of four type 2 RyR polypeptides (RyR2) and four FK506 binding proteins (FKBP12.6)...
  2. Lehnart S, Wehrens X, Laitinen P, Reiken S, Deng S, Cheng Z, et al. Sudden death in familial polymorphic ventricular tachycardia associated with calcium release channel (ryanodine receptor) leak. Circulation. 2004;109:3208-14 pubmed
    ..exercise-induced arrhythmias and sudden cardiac death due to missense mutations in the cardiac ryanodine receptor (RyR2), an intracellular Ca2+ release channel required for excitation-contraction coupling in the heart...
  3. Marx S, Reiken S, Hisamatsu Y, Gaburjakova M, Gaburjakova J, Yang Y, et al. Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers. J Cell Biol. 2001;153:699-708 pubmed
    ..Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents ..
  4. Tiso N, Salamon M, Bagattin A, Danieli G, Argenton F, Bortolussi M. The binding of the RyR2 calcium channel to its gating protein FKBP12.6 is oppositely affected by ARVD2 and VTSIP mutations. Biochem Biophys Res Commun. 2002;299:594-8 pubmed
    ..dysplasia/cardiomyopathy type 2 (ARVD2, OMIM 600996) and stress-induced polymorphic ventricular tachycardia (VTSIP, OMIM 604772) are two cardiac diseases causing juvenile sudden death, both associated with mutations in the RyR2 ..
  5. Johnson J, Kuang S, Misler S, Polonsky K. Ryanodine receptors in human pancreatic beta cells: localization and effects on insulin secretion. FASEB J. 2004;18:878-80 pubmed
    ..In diabetes, the expression and function of ryanodine receptor (RyR) Ca2+ release channels are reduced...
  6. Tiso N, Stephan D, Nava A, Bagattin A, Devaney J, Stanchi F, et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001;10:189-94 pubmed
    Arrhythmogenic right ventricular dysplasia type 2 (ARVD2, OMIM 600996) is an autosomal dominant cardiomyopathy, characterized by partial degeneration of the myocardium of the right ventricle, electrical instability and sudden death...
  7. Johnson J, Han Z, Otani K, Ye H, Zhang Y, Wu H, et al. RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets. J Biol Chem. 2004;279:24794-802 pubmed
    Cells are programmed to die when critical signaling and metabolic pathways are disrupted. Inhibiting the type 2 ryanodine receptor (RyR2) in human and mouse pancreatic beta-cells markedly increased apoptosis...
  8. Wang R, Bolstad J, Kong H, Zhang L, Brown C, Chen S. The predicted TM10 transmembrane sequence of the cardiac Ca2+ release channel (ryanodine receptor) is crucial for channel activation and gating. J Biol Chem. 2004;279:3635-42 pubmed
    ..of mutations of each residue within the 24-amino acid TM10 sequence of the mouse cardiac ryanodine receptor (RyR2) on channel activation by caffeine and Ca(2+)...
  9. Bhuiyan Z, van den Berg M, van Tintelen J, Bink Boelkens M, Wiesfeld A, Alders M, et al. Expanding spectrum of human RYR2-related disease: new electrocardiographic, structural, and genetic features. Circulation. 2007;116:1569-76 pubmed
    ..Conventional polymerase chain reaction-based screening did not reveal a mutation in either the Ryanodine receptor 2 gene (RYR2) or ACTN2, the most plausible candidate genes in the region of interest...
  10. Laitinen P, Swan H, Kontula K. Molecular genetics of exercise-induced polymorphic ventricular tachycardia: identification of three novel cardiac ryanodine receptor mutations and two common calsequestrin 2 amino-acid polymorphisms. Eur J Hum Genet. 2003;11:888-91 pubmed
    Mutations of two myocardial calcium signaling molecules, ryanodine receptor 2 (RYR2) and calsequestrin 2 (CASQ2), may cause catecholaminergic polymorphic ventricular tachycardia (CPVT), a severe inherited arrhythmic disease manifesting ..

Detail Information

Publications62

  1. Marx S, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, et al. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell. 2000;101:365-76 pubmed
    ..The channel is a tetramer comprised of four type 2 RyR polypeptides (RyR2) and four FK506 binding proteins (FKBP12.6)...
  2. Lehnart S, Wehrens X, Laitinen P, Reiken S, Deng S, Cheng Z, et al. Sudden death in familial polymorphic ventricular tachycardia associated with calcium release channel (ryanodine receptor) leak. Circulation. 2004;109:3208-14 pubmed
    ..exercise-induced arrhythmias and sudden cardiac death due to missense mutations in the cardiac ryanodine receptor (RyR2), an intracellular Ca2+ release channel required for excitation-contraction coupling in the heart...
  3. Marx S, Reiken S, Hisamatsu Y, Gaburjakova M, Gaburjakova J, Yang Y, et al. Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers. J Cell Biol. 2001;153:699-708 pubmed
    ..Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents ..
  4. Tiso N, Salamon M, Bagattin A, Danieli G, Argenton F, Bortolussi M. The binding of the RyR2 calcium channel to its gating protein FKBP12.6 is oppositely affected by ARVD2 and VTSIP mutations. Biochem Biophys Res Commun. 2002;299:594-8 pubmed
    ..dysplasia/cardiomyopathy type 2 (ARVD2, OMIM 600996) and stress-induced polymorphic ventricular tachycardia (VTSIP, OMIM 604772) are two cardiac diseases causing juvenile sudden death, both associated with mutations in the RyR2 ..
  5. Johnson J, Kuang S, Misler S, Polonsky K. Ryanodine receptors in human pancreatic beta cells: localization and effects on insulin secretion. FASEB J. 2004;18:878-80 pubmed
    ..In diabetes, the expression and function of ryanodine receptor (RyR) Ca2+ release channels are reduced...
  6. Tiso N, Stephan D, Nava A, Bagattin A, Devaney J, Stanchi F, et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001;10:189-94 pubmed
    Arrhythmogenic right ventricular dysplasia type 2 (ARVD2, OMIM 600996) is an autosomal dominant cardiomyopathy, characterized by partial degeneration of the myocardium of the right ventricle, electrical instability and sudden death...
  7. Johnson J, Han Z, Otani K, Ye H, Zhang Y, Wu H, et al. RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets. J Biol Chem. 2004;279:24794-802 pubmed
    Cells are programmed to die when critical signaling and metabolic pathways are disrupted. Inhibiting the type 2 ryanodine receptor (RyR2) in human and mouse pancreatic beta-cells markedly increased apoptosis...
  8. Wang R, Bolstad J, Kong H, Zhang L, Brown C, Chen S. The predicted TM10 transmembrane sequence of the cardiac Ca2+ release channel (ryanodine receptor) is crucial for channel activation and gating. J Biol Chem. 2004;279:3635-42 pubmed
    ..of mutations of each residue within the 24-amino acid TM10 sequence of the mouse cardiac ryanodine receptor (RyR2) on channel activation by caffeine and Ca(2+)...
  9. Bhuiyan Z, van den Berg M, van Tintelen J, Bink Boelkens M, Wiesfeld A, Alders M, et al. Expanding spectrum of human RYR2-related disease: new electrocardiographic, structural, and genetic features. Circulation. 2007;116:1569-76 pubmed
    ..Conventional polymerase chain reaction-based screening did not reveal a mutation in either the Ryanodine receptor 2 gene (RYR2) or ACTN2, the most plausible candidate genes in the region of interest...
  10. Laitinen P, Swan H, Kontula K. Molecular genetics of exercise-induced polymorphic ventricular tachycardia: identification of three novel cardiac ryanodine receptor mutations and two common calsequestrin 2 amino-acid polymorphisms. Eur J Hum Genet. 2003;11:888-91 pubmed
    Mutations of two myocardial calcium signaling molecules, ryanodine receptor 2 (RYR2) and calsequestrin 2 (CASQ2), may cause catecholaminergic polymorphic ventricular tachycardia (CPVT), a severe inherited arrhythmic disease manifesting ..
  11. George C, Higgs G, Lai F. Ryanodine receptor mutations associated with stress-induced ventricular tachycardia mediate increased calcium release in stimulated cardiomyocytes. Circ Res. 2003;93:531-40 pubmed
    Ca2+ release from the sarcoplasmic reticulum mediated by the cardiac ryanodine receptor (RyR2) is a fundamental event in cardiac muscle contraction...
  12. Denda S, Kumamoto J, Takei K, Tsutsumi M, Aoki H, Denda M. Ryanodine receptors are expressed in epidermal keratinocytes and associated with keratinocyte differentiation and epidermal permeability barrier homeostasis. J Invest Dermatol. 2012;132:69-75 pubmed publisher
    ..In the present study, we investigated the expression of RyR in human epidermis...
  13. Marciante K, Durda J, Heckbert S, Lumley T, Rice K, McKnight B, et al. Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011;21:280-8 pubmed publisher
    ..The bimodal response, rhabdomyolysis in a small proportion of users, points to genetic factors as a potential cause. We conducted a case-control study to evaluate genetic markers for cerivastatin-associated rhabdomyolysis...
  14. Takasawa S, Kuroki M, Nata K, Noguchi N, Ikeda T, Yamauchi A, et al. A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene. Biochem Biophys Res Commun. 2010;397:140-5 pubmed publisher
    ..screening a rat islet cDNA library, we isolated a novel RyR cDNA (the islet-type RyR), which is generated from the RyR2 gene by alternative splicing of exons 4 and 75...
  15. Treviño L, Yang W, French D, Hunger S, Carroll W, Devidas M, et al. Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nat Genet. 2009;41:1001-5 pubmed publisher
    ..86, respectively) and were associated with methotrexate accumulation and gene expression pattern in leukemic lymphoblasts. We conclude that germline variants affect susceptibility to, and characteristics of, specific ALL subtypes. ..
  16. Girard T, Cavagna D, Padovan E, Spagnoli G, Urwyler A, Zorzato F, et al. B-lymphocytes from malignant hyperthermia-susceptible patients have an increased sensitivity to skeletal muscle ryanodine receptor activators. J Biol Chem. 2001;276:48077-82 pubmed
    ..B-cells from MH-susceptible individuals carrying the V2168M RYR1 gene mutation were more sensitive to the RYR activator 4-chloro-m-cresol and (ii) their peripheral blood leukocytes produce more interleukin (IL)-1beta after ..
  17. Kong H, Wang R, Chen W, Zhang L, Chen K, Shimoni Y, et al. Skeletal and cardiac ryanodine receptors exhibit different responses to Ca2+ overload and luminal ca2+. Biophys J. 2007;92:2757-70 pubmed
    ..In this study, we investigated the SOICR properties of HEK293 cells expressing RyR1 or RyR2. We found that HEK293 cells expressing RyR2 exhibited robust SOICR activity, whereas no SOICR activity was observed ..
  18. Kawamura M, Ohno S, Naiki N, Nagaoka I, Dochi K, Wang Q, et al. Genetic background of catecholaminergic polymorphic ventricular tachycardia in Japan. Circ J. 2013;77:1705-13 pubmed
    ..clinical criteria for CPVT, genetic testing was conducted in all exons on 3 CPVT-related genes: cardiac ryanodine receptor 2 (RYR2), calsequestrin 2 (CASQ2) and inward rectifier potassium channel 2 (KCNJ2), and the clinical features ..
  19. Ambalavanan A, Girard S, Ahn K, Zhou S, Dionne Laporte A, Spiegelman D, et al. De novo variants in sporadic cases of childhood onset schizophrenia. Eur J Hum Genet. 2016;24:944-8 pubmed publisher
    ..Among the genes found disrupted in our study, SEZ6, RYR2, GPR153, GTF2IRD1, TTBK1 and ITGA6 have been previously linked to neuronal function or to psychiatric disorders, ..
  20. Terentyev D, Hamilton S. Regulation of sarcoplasmic reticulum Ca2+ release by serine-threonine phosphatases in the heart. J Mol Cell Cardiol. 2016;101:156-164 pubmed publisher
    ..Reversible phosphorylation of the SR Ca2+ release channel, ryanodine receptor type 2 (RyR2) is the central mechanism of regulation of Ca2+ release in cardiomyocytes...
  21. Handhle A, Ormonde C, Thomas N, Bralesford C, Williams A, Lai F, et al. Calsequestrin interacts directly with the cardiac ryanodine receptor luminal domain. J Cell Sci. 2016;129:3983-3988 pubmed
    ..sarcoplasmic reticulum (SR) Ca2+ release mediated by the quaternary complex comprising the ryanodine receptor 2 (RyR2), calsequestrin 2 (CSQ2), junctin (encoded by ASPH) and triadin...
  22. Munro M, Jayasinghe I, Wang Q, Quick A, Wang W, Baddeley D, et al. Junctophilin-2 in the nanoscale organisation and functional signalling of ryanodine receptor clusters in cardiomyocytes. J Cell Sci. 2016;129:4388-4398 pubmed
    ..protein within it, the ryanodine receptor (RyR; in this paper, we use RyR to refer to the myocardial isoform RyR2)...
  23. Yamazaki D, Yamazaki T, Takeshima H. New molecular components supporting ryanodine receptor-mediated Ca(2+) release: roles of junctophilin and TRIC channel in embryonic cardiomyocytes. Pharmacol Ther. 2009;121:265-72 pubmed publisher
    ..This review focuses on cardiac Ca(2+) release by discussing pathological defects of mutant cardiomyocytes lacking ryanodine receptors, junctophilins, or TRIC channels. ..
  24. Song T, Zheng Y, Wang Y. Cross Talk Between Mitochondrial Reactive Oxygen Species and Sarcoplasmic Reticulum Calcium in Pulmonary Arterial Smooth Muscle Cells. Adv Exp Med Biol. 2017;967:289-298 pubmed publisher
    ..Ryanodine receptor-2 (RyR2)/Ca2+ release channel on the sarcoplasmic reticulum (SR) serves as a most valuable player in the ..
  25. Sedej S, Heinzel F, Walther S, Dybkova N, Wakula P, Groborz J, et al. Na+-dependent SR Ca2+ overload induces arrhythmogenic events in mouse cardiomyocytes with a human CPVT mutation. Cardiovasc Res. 2010;87:50-9 pubmed publisher
    Mutations in the cardiac ryanodine receptor Ca(2+) release channel, RyR2, underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited life-threatening arrhythmia...
  26. Wilson D, Ermentrout B, Nemec J, Salama G. A model of cardiac ryanodine receptor gating predicts experimental Ca2+-dynamics and Ca2+-triggered arrhythmia in the long QT syndrome. Chaos. 2017;27:093940 pubmed publisher
    ..are reproduced in a modified 0-dimensional model, where 3 gates in series control the ryanodine receptor (RyR2) conductance...
  27. Novak A, Barad L, Lorber A, Gherghiceanu M, Reiter I, Eisen B, et al. Functional abnormalities in iPSC-derived cardiomyocytes generated from CPVT1 and CPVT2 patients carrying ryanodine or calsequestrin mutations. J Cell Mol Med. 2015;19:2006-18 pubmed publisher
    ..CPVT is caused by abnormal intracellular Ca(2+) handling resulting from mutations in the RyR2 or CASQ2 genes...
  28. Uehara A, Murayama T, Yasukochi M, Fill M, Horie M, Okamoto T, et al. Extensive Ca2+ leak through K4750Q cardiac ryanodine receptors caused by cytosolic and luminal Ca2+ hypersensitivity. J Gen Physiol. 2017;149:199-218 pubmed publisher
    Various ryanodine receptor 2 (RyR2) point mutations cause catecholamine-induced polymorphic ventricular tachycardia (CPVT), a life-threatening arrhythmia evoked by diastolic intracellular Ca2+ release dysfunction...
  29. Borchert T, Hübscher D, Guessoum C, Lam T, Ghadri J, Schellinger I, et al. Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy. J Am Coll Cardiol. 2017;70:975-991 pubmed publisher
    ..levels; and cyclic adenosine monophosphate-dependent protein kinase A-mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay...
  30. Viitasalo M, Oikarinen L, Vaananen H, Kontula K, Toivonen L, Swan H. U-waves and T-wave peak to T-wave end intervals in patients with catecholaminergic polymorphic ventricular tachycardia, effects of beta-blockers. Heart Rhythm. 2008;5:1382-8 pubmed publisher
    ..We reviewed Holter recordings from 19 CPVT patients with a RyR2 mutation (P2328S or V4653F) and from 19 healthy unaffected subjects to record U-waves and TPE intervals as well as ..
  31. Oda T, Yang Y, Nitu F, Svensson B, Lu X, Fruen B, et al. In cardiomyocytes, binding of unzipping peptide activates ryanodine receptor 2 and reciprocally inhibits calmodulin binding. Circ Res. 2013;112:487-97 pubmed publisher
    One hypothesis for elevated Ca(2+) leak through cardiac ryanodine receptors (ryanodine receptor 2 [RyR2]) in heart failure is interdomain unzipping that can enhance aberrant channel activation...
  32. Bruno A, Huang J, Bennett D, Marr R, Hastings M, Stutzmann G. Altered ryanodine receptor expression in mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2012;33:1001.e1-6 pubmed publisher
    ..Here, we compare mRNA levels of the RyR2 and RyR3 isoforms as well as specific alternatively spliced variants across vulnerable brain regions from ..
  33. Aizawa Y, Ueda K, Komura S, Washizuka T, Chinushi M, Inagaki N, et al. A novel mutation in FKBP12.6 binding region of the human cardiac ryanodine receptor gene (R2401H) in a Japanese patient with catecholaminergic polymorphic ventricular tachycardia. Int J Cardiol. 2005;99:343-5 pubmed
    ..The human cardiac ryanodine receptor gene (RyR2) was linked to CPVT...
  34. Lehnart S, Wehrens X, Reiken S, Warrier S, Belevych A, Harvey R, et al. Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias. Cell. 2005;123:25-35 pubmed
    ..The phosphodiesterase 4D3 (PDE4D3) was found in the cardiac ryanodine receptor (RyR2)/calcium-release-channel complex (required for excitation-contraction [EC] coupling in heart muscle)...
  35. Ding L, Abebe T, Beyene J, Wilke R, Goldberg A, Woo J, et al. Rank-based genome-wide analysis reveals the association of ryanodine receptor-2 gene variants with childhood asthma among human populations. Hum Genomics. 2013;7:16 pubmed publisher
    ..b>Ryanodine receptor 2 (RYR2, a statin response-related gene) showed the strongest association in European (p value=2...
  36. Fejzo M, Myhre R, Colodro Conde L, MacGibbon K, Sinsheimer J, Reddy M, et al. Genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2). Mol Cell Endocrinol. 2017;439:308-316 pubmed publisher
    ..Variants in RYR2 segregated with disease in 2 families. The novel variant L3277R was not found in any case/control...
  37. Thomas N, George C, Lai F. Role of ryanodine receptor mutations in cardiac pathology: more questions than answers?. Biochem Soc Trans. 2006;34:913-8 pubmed
    ..Recently, single-residue mutations in the cardiac RyR (RyR2) have been identified in families that exhibit CPVT (catecholaminergic polymorphic ventricular tachycardia), a ..
  38. Pluteanu F, Nikonova Y, Holzapfel A, Herzog B, Scherer A, Preisenberger J, et al. Progressive impairment of atrial myocyte function during left ventricular hypertrophy and heart failure. J Mol Cell Cardiol. 2017;: pubmed publisher
    ..in SHR the expression and phosphorylation of SR Ca2+-regulating proteins (SERCA2a, calsequestrin, RyR2 and phospholamban) showed negative correlation with increasing lung weight...
  39. Tsai F, Lin Y, Chang S, Chang G, Hsu Y, Lin Y, et al. Differential left-to-right atria gene expression ratio in human sinus rhythm and atrial fibrillation: Implications for arrhythmogenesis and thrombogenesis. Int J Cardiol. 2016;222:104-112 pubmed publisher
    ..Targeting the molecular mechanisms underlying the LA-to-RA difference and AF-related remodeling in the LA appendage may help provide new therapeutic options in treating AF and preventing thromboembolism in AF. ..
  40. Mizuno K, Kurokawa K, Ohkuma S. Regulatory mechanisms and pathophysiological significance of IP3 receptors and ryanodine receptors in drug dependence. J Pharmacol Sci. 2013;123:306-11 pubmed
    ..Although previous reports showed that the most important regulators of both RyR and IP3R channel functions are changes in the intracellular Ca(2+) concentration and in phosphorylation of these ..