RYR1_HUMAN
ID RYR1_HUMAN Reviewed; 5038 AA.
AC P21817; Q16314; Q16368; Q9NPK1; Q9P1U4;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 3.
DT 03-AUG-2022, entry version 237.
DE RecName: Full=Ryanodine receptor 1;
DE Short=RYR-1;
DE Short=RyR1;
DE AltName: Full=Skeletal muscle calcium release channel;
DE AltName: Full=Skeletal muscle ryanodine receptor;
DE AltName: Full=Skeletal muscle-type ryanodine receptor;
DE AltName: Full=Type 1 ryanodine receptor;
GN Name=RYR1; Synonyms=RYDR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Skeletal muscle;
RX PubMed=2298749; DOI=10.1016/s0021-9258(19)39968-5;
RA Zorzato F., Fujii J., Otsu K., Phillips M.S., Green N.M., Lai F.A.,
RA Meissner G., Maclennan D.H.;
RT "Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+
RT release channel (ryanodine receptor) of skeletal muscle sarcoplasmic
RT reticulum.";
RL J. Biol. Chem. 265:2244-2256(1990).
RN [2]
RP SEQUENCE REVISION TO 2324; 2840 AND 3380, INVOLVEMENT IN MHS1, VARIANT MHS1
RP ARG-248, AND VARIANTS CYS-471; LEU-1787; CYS-2060 AND VAL-2550.
RC TISSUE=Muscle;
RX PubMed=1354642; DOI=10.1016/0888-7543(92)90042-q;
RA Gillard E.F., Otsu K., Fujii J., Duff C.L., de Leon S., Khanna V.K.,
RA Britt B.A., Worton R.G., McLennan D.H.;
RT "Polymorphisms and deduced amino acid substitutions in the coding sequence
RT of the ryanodine receptor (RYR1) gene in individuals with malignant
RT hyperthermia.";
RL Genomics 13:1247-1254(1992).
RN [3]
RP SEQUENCE REVISION TO 1365-1368, VARIANT CCD HIS-2435, AND ALTERNATIVE
RP SPLICING.
RC TISSUE=Muscle;
RX PubMed=8220422; DOI=10.1038/ng0993-46;
RA Zhang Y., Chen H.S., Khanna V.K., de Leon S., Phillips M.S.,
RA Schappert K.T., Britt B.A., Brownell A.K.W., McLennan D.H.;
RT "A mutation in the human ryanodine receptor gene associated with central
RT core disease.";
RL Nat. Genet. 5:46-50(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND VARIANTS
RP ALA-1832 AND VAL-2550.
RX PubMed=8661021; DOI=10.1006/geno.1996.0238;
RA Phillips M.S., Fujii J., Khanna V.K., de Leon S., Yokobata K.,
RA de Jong P.J., McLennan D.H.;
RT "The structural organization of the human skeletal muscle ryanodine
RT receptor (RYR1) gene.";
RL Genomics 34:24-41(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 598-722.
RC TISSUE=Skeletal muscle;
RX PubMed=1639409; DOI=10.1016/0888-7543(92)90163-m;
RA Otsu K., Phillips M.S., Khanna V.K., de Leon S., McLennan D.H.;
RT "Refinement of diagnostic assays for a probable causal mutation for porcine
RT and human malignant hyperthermia.";
RL Genomics 13:835-837(1992).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 603-641, AND VARIANT MHS1 CYS-614.
RX PubMed=1774074; DOI=10.1016/0888-7543(91)90084-r;
RA Gillard E.F., Otsu K., Fujii J., Khanna V.K., de Leon S., Derdemezi J.,
RA Britt B.A., Duff C.L., Worton R.G., MacLennan D.H.;
RT "A substitution of cysteine for arginine 614 in the ryanodine receptor is
RT potentially causative of human malignant hyperthermia.";
RL Genomics 11:751-755(1991).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 603-627, AND VARIANT MHS1 CYS-614.
RX PubMed=7751854; DOI=10.1007/bf00936884;
RA Moroni I., Gonano E.F., Comi G.P., Tegazzin V., Prelle A., Bordoni A.,
RA Bresolin N., Scarlato G.;
RT "Ryanodine receptor gene point mutation and malignant hyperthermia
RT susceptibility.";
RL J. Neurol. 242:127-133(1995).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4696-4974, AND SUBCELLULAR LOCATION.
RC TISSUE=Myometrium;
RX PubMed=7556644; DOI=10.1016/0014-5793(95)00924-x;
RA Lynn S., Morgan J.M., Lamb H.K., Meissner G., Gillespie J.I.;
RT "Isolation and partial cloning of ryanodine-sensitive Ca2+ release channel
RT protein isoforms from human myometrial smooth muscle.";
RL FEBS Lett. 372:6-12(1995).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=9607712; DOI=10.1016/s0306-4522(97)00612-x;
RA Martin C., Chapman K.E., Seckl J.R., Ashley R.H.;
RT "Partial cloning and differential expression of ryanodine receptor/calcium-
RT release channel genes in human tissues including the hippocampus and
RT cerebellum.";
RL Neuroscience 85:205-216(1998).
RN [11]
RP INTERACTION WITH CALM AND S100A1, AND ACTIVITY REGULATION.
RX PubMed=18650434; DOI=10.1074/jbc.m804432200;
RA Wright N.T., Prosser B.L., Varney K.M., Zimmer D.B., Schneider M.F.,
RA Weber D.J.;
RT "S100A1 and calmodulin compete for the same binding site on ryanodine
RT receptor.";
RL J. Biol. Chem. 283:26676-26683(2008).
RN [12]
RP INVOLVEMENT IN KDS, AND VARIANT KDS GLU-33.
RX PubMed=18765655; DOI=10.1212/01.wnl.0000324929.33780.2f;
RA D'Arcy C.E., Bjorksten A., Yiu E.M., Bankier A., Gillies R., McLean C.A.,
RA Shield L.K., Ryan M.M.;
RT "King-denborough syndrome caused by a novel mutation in the ryanodine
RT receptor gene.";
RL Neurology 71:776-777(2008).
RN [13]
RP FUNCTION, PHOSPHORYLATION AT SER-2843, S-NITROSYLATION, AND IDENTIFICATION
RP IN A COMPLEX WITH PDE4D; PKA; FKBP1A AND PROTEIN PHOSPHATASE 1.
RX PubMed=18268335; DOI=10.1073/pnas.0711074105;
RA Bellinger A.M., Reiken S., Dura M., Murphy P.W., Deng S.X., Landry D.W.,
RA Nieman D., Lehnart S.E., Samaru M., LaCampagne A., Marks A.R.;
RT "Remodeling of ryanodine receptor complex causes 'leaky' channels: a
RT molecular mechanism for decreased exercise capacity.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:2198-2202(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-4864 AND SER-4867, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [15]
RP REVIEW.
RX PubMed=20961976; DOI=10.1101/cshperspect.a003996;
RA Lanner J.T., Georgiou D.K., Joshi A.D., Hamilton S.L.;
RT "Ryanodine receptors: structure, expression, molecular details, and
RT function in calcium release.";
RL Cold Spring Harb. Perspect. Biol. 2:E3996-E3996(2010).
RN [16]
RP INVOLVEMENT IN KDS, AND VARIANTS KDS ARG-2206; TRP-2452 AND PHE-2776.
RX PubMed=21514828; DOI=10.1016/j.nmd.2011.03.006;
RA Dowling J.J., Lillis S., Amburgey K., Zhou H., Al-Sarraj S., Buk S.J.,
RA Wraige E., Chow G., Abbs S., Leber S., Lachlan K., Baralle D., Taylor A.,
RA Sewry C., Muntoni F., Jungbluth H.;
RT "King-Denborough syndrome with and without mutations in the skeletal muscle
RT ryanodine receptor (RYR1) gene.";
RL Neuromuscul. Disord. 21:420-427(2011).
RN [17]
RP INVOLVEMENT IN SAMARITAN MYOPATHY, AND VARIANT CYS-1088.
RX PubMed=22752422; DOI=10.1007/s00401-012-1007-3;
RA Bohm J., Leshinsky-Silver E., Vassilopoulos S., Le Gras S.,
RA Lerman-Sagie T., Ginzberg M., Jost B., Lev D., Laporte J.;
RT "Samaritan myopathy, an ultimately benign congenital myopathy, is caused by
RT a RYR1 mutation.";
RL Acta Neuropathol. 124:575-581(2012).
RN [18]
RP INVOLVEMENT IN KDS, AND VARIANT KDS CYS-2508.
RX PubMed=27918309; DOI=10.1213/xaa.0000000000000421;
RA Joseph M.R., Theroux M.C., Mooney J.J., Falitz S., Brandom B.W.,
RA Byler D.L.;
RT "Intraoperative Presentation of Malignant Hyperthermia (Confirmed by RYR1
RT Gene Mutation, c.7522C>T; p.R2508C) Leads to Diagnosis of King-Denborough
RT Syndrome in a Child With Hypotonia and Dysmorphic Features: A Case
RT Report.";
RL A. A. Case Rep. 8:55-57(2017).
RN [19]
RP VARIANTS CCD CYS-163 AND MET-403, AND VARIANTS MHS1 CYS-163 AND MET-403.
RX PubMed=8220423; DOI=10.1038/ng0993-51;
RA Quane K.A., Healy J.M.S., Keating K.E., Manning B.M., Couch F.J.,
RA Palmucci L.M., Doriguzzi C., Fagerlund T.H., Berg K., Ording H.,
RA Bendixen D., Mortier W., Linz U., Muller C.R., McCarthy T.V.;
RT "Mutations in the ryanodine receptor gene in central core disease and
RT malignant hyperthermia.";
RL Nat. Genet. 5:51-55(1993).
RN [20]
RP VARIANT CCD SER-522.
RX PubMed=7829078; DOI=10.1006/geno.1994.1483;
RA Quane K.A., Keating K.E., Healy J.M.S., Manning B.M., Krivosic-Horber R.,
RA Krivosic I., Monnier N., Lunardi J., McCarthy T.V.;
RT "Mutation screening of the RYR1 gene in malignant hyperthermia: detection
RT of a novel Tyr to Ser mutation in a pedigree with associated central
RT cores.";
RL Genomics 23:236-239(1994).
RN [21]
RP VARIANT MHS1 ARG-341.
RX PubMed=8012359; DOI=10.1093/hmg/3.3.471;
RA Quane K.A., Keating K.E., Manning B.M., Healy J.M.S., Monsieurs K.,
RA Heffron J.J.A., Lehane M., Heytens L., Krivosic-Horber R., Adnet P.,
RA Ellis F.R., Monnier N., Lunardi J., McCarthy T.V.;
RT "Detection of a novel common mutation in the ryanodine receptor gene in
RT malignant hyperthermia: implications for diagnosis and heterogeneity
RT studies.";
RL Hum. Mol. Genet. 3:471-476(1994).
RN [22]
RP VARIANT MHS1 ARG-2434.
RX PubMed=7849712; DOI=10.1093/hmg/3.10.1855;
RA Keating K.E., Quane K.A., Manning B.M., Lehane M., Hartung E., Censier K.,
RA Urwyler A., Klausnitzer M., Muller C.R., Heffron J.J.A., McCarthy T.V.;
RT "Detection of a novel RYR1 mutation in four malignant hyperthermia
RT pedigrees.";
RL Hum. Mol. Genet. 3:1855-1858(1994).
RN [23]
RP VARIANT MHS1 ARG-2434.
RX PubMed=7881417; DOI=10.1093/hmg/3.12.2181;
RA Phillips M.S., Khanna V.K., de Leon S., Frodis W., Britt B.A.,
RA McLennan D.H.;
RT "The substitution of Arg for Gly2433 in the human skeletal muscle ryanodine
RT receptor is associated with malignant hyperthermia.";
RL Hum. Mol. Genet. 3:2181-2186(1994).
RN [24]
RP VARIANT MHS1 ARG-35.
RX PubMed=9066328; DOI=10.1097/00000542-199703000-00014;
RA Lynch P.J., Krivosic-Horber R., Reyford H., Monnier N., Quane K.A.,
RA Adnet P., Haudecoeur G., Krivosic I., McCarthy T.V., Lunardi J.;
RT "Identification of heterozygous and homozygous individuals with the novel
RT RYR1 mutation Cys35Arg in a large kindred.";
RL Anesthesiology 86:620-626(1997).
RN [25]
RP VARIANT MHS1 LEU-614.
RX PubMed=9389851; DOI=10.1093/bja/79.3.332;
RA Quane K.A., Ording H., Keating K.E., Manning B.M., Heine R., Bendixen D.,
RA Berg K., Krivosic-Horber R., Lehmann-Horn F., Fagerlund T.H.,
RA McCarthy T.V.;
RT "Detection of a novel mutation at amino acid position 614 in the ryanodine
RT receptor in malignant hyperthermia.";
RL Br. J. Anaesth. 79:332-337(1997).
RN [26]
RP VARIANT MHS1 TRP-552.
RX PubMed=9138151; DOI=10.1136/jmg.34.4.291;
RA Keating K.E., Giblin L., Lynch P.J., Quane K.A., Lehane M., Heffron J.J.A.,
RA McCarthy T.V.;
RT "Detection of a novel mutation in the ryanodine receptor gene in an Irish
RT malignant hyperthermia pedigree: correlation of the IVCT response with the
RT affected and unaffected haplotypes.";
RL J. Med. Genet. 34:291-296(1997).
RN [27]
RP VARIANTS MHS1 CYS-2163; MET-2168 AND MET-2206, AND VARIANT CCD/MHS1
RP HIS-2163.
RX PubMed=9497245; DOI=10.1086/301748;
RA Manning B.M., Quane K.A., Ording H., Urwyler A., Tegazzin V., Lehane M.,
RA O'Halloran J., Hartung E., Giblin L.M., Lynch P.J., Vaughan P., Censier K.,
RA Bendixen D., Comi G.P., Heytens L., Monsieurs K., Fagerlund T.H., Wolz W.,
RA Heffron J.J.A., Mueller C.R., McCarthy T.V.;
RT "Identification of novel mutations in the ryanodine-receptor gene (RYR1) in
RT malignant hyperthermia: genotype-phenotype correlation.";
RL Am. J. Hum. Genet. 62:599-609(1998).
RN [28]
RP VARIANTS MHS1 CYS-2458 AND HIS-2458.
RX PubMed=9450902;
RX DOI=10.1002/(sici)1098-1004(1998)11:1<45::aid-humu7>3.0.co;2-k;
RA Manning B.M., Quane K.A., Lynch P.J., Urwyler A., Tegazzin V.,
RA Krivosic-Horber R., Censier K., Comi G.P., Adnet P., Wolz W., Lunardi J.,
RA Muller C.R., McCarthy T.V.;
RT "Novel mutations at a CpG dinucleotide in the ryanodine receptor in
RT malignant hyperthermia.";
RL Hum. Mutat. 11:45-50(1998).
RN [29]
RP VARIANTS MHS1.
RX PubMed=10484775; DOI=10.1093/hmg/8.11.2055;
RA Brandt A., Schleithoff L., Jurkat-Rott K., Klingler W., Baur C.,
RA Lehmann-Horn F.;
RT "Screening of the ryanodine receptor gene in 105 malignant hyperthermia
RT families: novel mutations and concordance with the in vitro contracture
RT test.";
RL Hum. Mol. Genet. 8:2055-2062(1999).
RN [30]
RP VARIANTS MHS1 LEU-2435 AND HIS-2454.
RX PubMed=10051009;
RA Barone V., Massa O., Intravaia E., Bracco A., Di Martino A., Tegazzin V.,
RA Cozzolino S., Sorrentino V.;
RT "Mutation screening of the RYR1 gene and identification of two novel
RT mutations in Italian malignant hyperthermia families.";
RL J. Med. Genet. 36:115-118(1999).
RN [31]
RP VARIANT CCD THR-4898, AND CHARACTERIZATION OF VARIANT CCD THR-4898.
RX PubMed=10097181; DOI=10.1073/pnas.96.7.4164;
RA Lynch P.J., Tong J., Lehane M., Mallet A., Giblin L., Heffron J.J.A.,
RA Vaughan P., Zafra G., MacLennan D.H., McCarthy T.V.;
RT "A mutation in the transmembrane/luminal domain of the ryanodine receptor
RT is associated with abnormal Ca(2+) release channel function and severe
RT central core disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:4164-4169(1999).
RN [32]
RP VARIANTS MHS1 TRP-2452 AND HIS-2454.
RX PubMed=10823104; DOI=10.1093/oxfordjournals.bja.a013478;
RA Chamley D., Pollock N.A., Stowell K.M., Brown R.L.;
RT "Malignant hyperthermia in infancy and identification of novel RYR1
RT mutation.";
RL Br. J. Anaesth. 84:500-504(2000).
RN [33]
RP VARIANT MHS1 ILE-4826.
RX PubMed=10888602; DOI=10.1093/hmg/9.10.1515;
RA Brown R.L., Pollock A.N., Couchman K.G., Hodges M., Hutchinson D.O.,
RA Waaka R., Lynch P., McCarthy T.V., Stowell K.M.;
RT "A novel ryanodine receptor mutation and genotype-phenotype correlation in
RT a large malignant hyperthermia New Zealand Maori pedigree.";
RL Hum. Mol. Genet. 9:1515-1524(2000).
RN [34]
RP VARIANT MHS1 CYS-2454.
RX PubMed=10612851;
RX DOI=10.1002/(sici)1098-1004(200001)15:1<122::aid-humu40>3.0.co;2-a;
RA Gencik M., Gencik A., Mortier W., Epplen J.T.;
RT "Novel mutation in the RYR1 gene (R2454C) in a patient with malignant
RT hyperthermia.";
RL Hum. Mutat. 15:122-122(2000).
RN [35]
RP VARIANT CCD ALA-4637.
RX PubMed=11113224; DOI=10.1212/wnl.55.11.1689;
RA Scacheri P.C., Hoffman E.P., Fratkin J.D., Semino-Mora C., Senchak A.,
RA Davis M.R., Laing N.G., Vedanarayanan V., Subramony S.H.;
RT "A novel ryanodine receptor gene mutation causing both cores and rods in
RT congenital myopathy.";
RL Neurology 55:1689-1696(2000).
RN [36]
RP VARIANT MHS1 GLU-2347 DEL.
RX PubMed=11389482; DOI=10.1086/321270;
RA Sambuughin N., McWilliams S., de Bantel A., Sivakumar K., Nelson T.E.;
RT "Single-amino-acid deletion in the RYR1 gene, associated with malignant
RT hyperthermia susceptibility and unusual contraction phenotype.";
RL Am. J. Hum. Genet. 69:204-208(2001).
RN [37]
RP VARIANTS MHS1 CYS-163; ARG-248; CYS-614; MET-2168; MET-2206; ILE-2214;
RP THR-2367; ASN-2431; ARG-2434 AND HIS-2454.
RX PubMed=11575529; DOI=10.1097/00000542-200109000-00009;
RA Sambuughin N., Sei Y., Gallagher K.L., Wyre H.W., Madsen D., Nelson T.E.,
RA Fletcher J.E., Rosenberg H., Muldoon S.M.;
RT "North American malignant hyperthermia population: screening of the
RT ryanodine receptor gene and identification of novel mutations.";
RL Anesthesiology 95:594-599(2001).
RN [38]
RP VARIANTS CCD MET-2168; 4214-ARG--4216-PHE DEL; 4647-LEU-SER-4648 DEL;
RP PRO-4793; CYS-4796; CYS-4825; PHE-4860 DEL; HIS-4861; TRP-4893; THR-4898;
RP GLU-4899 AND GLY-4914.
RX PubMed=11709545; DOI=10.1093/hmg/10.22.2581;
RA Monnier N., Romero N.B., Lerale J., Landrieu P., Nivoche Y., Fardeau M.,
RA Lunardi J.;
RT "Familial and sporadic forms of central core disease are associated with
RT mutations in the C-terminal domain of the skeletal muscle ryanodine
RT receptor.";
RL Hum. Mol. Genet. 10:2581-2592(2001).
RN [39]
RP VARIANTS CCD HIS-4861; ARG-4891; THR-4898; ARG-4899 AND VAL-4906,
RP CHARACTERIZATION OF VARIANTS CCD MET-2168; HIS-4861; TRP-4893; THR-4898 AND
RP ARG-4899, AND FUNCTION.
RX PubMed=11741831; DOI=10.1093/hmg/10.25.2879;
RA Tilgen N., Zorzato F., Halliger-Keller B., Muntoni F., Sewry C.,
RA Palmucci L.M., Schneider C., Hauser E., Lehmann-Horn F., Mueller C.R.,
RA Treves S.;
RT "Identification of four novel mutations in the C-terminal membrane spanning
RT domain of the ryanodine receptor 1: association with central core disease
RT and alteration of calcium homeostasis.";
RL Hum. Mol. Genet. 10:2879-2887(2001).
RN [40]
RP VARIANT MHS1 GLU-2129.
RX PubMed=11241852; DOI=10.1002/humu.15;
RA Rueffert H., Kraus H., Olthoff D., Deutrich C., Froster U.G.;
RT "Identification of a novel mutation in the ryanodine receptor gene (RYR1)
RT in patients with malignant hyperthermia.";
RL Hum. Mutat. 17:238-238(2001).
RN [41]
RP VARIANT MHS1 THR-2350, AND CHARACTERIZATION OF VARIANT MHS1 THR-2350.
RX PubMed=11525881; DOI=10.1016/s0960-8966(01)00202-4;
RA Sambuughin N., Nelson T.E., Jankovic J., Xin C., Meissner G.,
RA Mullakandov M., Ji J., Rosenberg H., Sivakumar K., Goldfarb L.G.;
RT "Identification and functional characterization of a novel ryanodine
RT receptor mutation causing malignant hyperthermia in North American and
RT South American families.";
RL Neuromuscul. Disord. 11:530-537(2001).
RN [42]
RP VARIANTS MHS1 CYS-163; ASN-166; ARG-341; HIS-401; CYS-614; GLU-2129;
RP MET-2168; MET-2206; THR-2428; ARG-2434; HIS-2435; TRP-2452 AND HIS-2454.
RX PubMed=12059893; DOI=10.1034/j.1399-6576.2002.460610.x;
RA Rueffert H., Olthoff D., Deutrich C., Meinecke C.D., Froster U.G.;
RT "Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients
RT susceptible to malignant hyperthermia who show definite IVCT results:
RT identification of three novel mutations.";
RL Acta Anaesthesiol. Scand. 46:692-698(2002).
RN [43]
RP VARIANTS MHS1 CYS-163; ARG-341; CYS-614; CYS-2454; MET-3916 AND LEU-4973.
RX PubMed=12411788; DOI=10.1097/00000542-200211000-00007;
RA Monnier N., Krivosic-Horber R., Payen J.-F., Kozak-Ribbens G., Nivoche Y.,
RA Adnet P., Reyford H., Lunardi J.;
RT "Presence of two different genetic traits in malignant hyperthermia
RT families: implication for genetic analysis, diagnosis, and incidence of
RT malignant hyperthermia susceptibility.";
RL Anesthesiology 97:1067-1074(2002).
RN [44]
RP VARIANT CCD SER-3527.
RX PubMed=12112081; DOI=10.1002/ana.10231;
RA Ferreiro A., Monnier N., Romero N.B., Leroy J.-P., Boennemann C.,
RA Haenggeli C.-A., Straub V., Voss W.D., Nivoche Y., Jungbluth H.,
RA Lemainque A., Voit T., Lunardi J., Fardeau M., Guicheney P.;
RT "A recessive form of central core disease, transiently presenting as multi-
RT minicore disease, is associated with a homozygous mutation in the ryanodine
RT receptor type 1 gene.";
RL Ann. Neurol. 51:750-759(2002).
RN [45]
RP VARIANT MHS1 CYS-401.
RX PubMed=12066726; DOI=10.1093/bja/88.4.508;
RA Davis M., Brown R., Dickson A., Horton H., James D., Laing N., Marston R.,
RA Norgate M., Perlman D., Pollock N., Stowell K.;
RT "Malignant hyperthermia associated with exercise-induced rhabdomyolysis or
RT congenital abnormalities and a novel RYR1 mutation in New Zealand and
RT Australian pedigrees.";
RL Br. J. Anaesth. 88:508-515(2002).
RN [46]
RP VARIANTS MHS1 CYS-163; CYS-401; HIS-2163; MET-2206; ILE-2280; ARG-2434;
RP LEU-2435; CYS-2458; SER-4136; LEU-4234; TRP-4737; VAL-4942 AND LEU-4973.
RX PubMed=12208234; DOI=10.1016/s0143-4160(02)00138-0;
RA Galli L., Orrico A., Cozzolino S., Pietrini V., Tegazzin V., Sorrentino V.;
RT "Mutations in the RYR1 gene in Italian patients at risk for malignant
RT hyperthermia: evidence for a cluster of novel mutations in the C-terminal
RT region.";
RL Cell Calcium 32:143-151(2002).
RN [47]
RP VARIANT MHS1 CYS-2355.
RX PubMed=12123492; DOI=10.1034/j.1399-0004.2002.620111.x;
RA McWilliams S., Nelson T., Sudo R.T., Zapata-Sudo G., Batti M.,
RA Sambuughin N.;
RT "Novel skeletal muscle ryanodine receptor mutation in a large Brazilian
RT family with malignant hyperthermia.";
RL Clin. Genet. 62:80-83(2002).
RN [48]
RP VARIANT MHS1 VAL-4838, AND VARIANTS ALA-1832; GLU-3756 AND SER-4668.
RX PubMed=11928716; DOI=10.1254/jjp.88.159;
RA Oyamada H., Oguchi K., Saitoh N., Yamazawa T., Hirose K., Kawana Y.,
RA Wakatsuki K., Oguchi K., Tagami M., Hanaoka K., Endo M., Iino M.;
RT "Novel mutations in C-terminal channel region of the ryanodine receptor in
RT malignant hyperthermia patients.";
RL Jpn. J. Pharmacol. 88:159-166(2002).
RN [49]
RP VARIANT CCD ILE-4849.
RX PubMed=12136074; DOI=10.1212/wnl.59.2.284;
RA Jungbluth H., Muller C.R., Halliger-Keller B., Brockington M., Brown S.C.,
RA Feng L., Chattopadhyay A., Mercuri E., Manzur A.Y., Ferreiro A.,
RA Laing N.G., Davis M.R., Roper H.P., Dubowitz V., Bydder G., Sewry C.A.,
RA Muntoni F.;
RT "Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy
RT with cores.";
RL Neurology 59:284-287(2002).
RN [50]
RP VARIANT MHS1 TRP-328, AND CHARACTERIZATION OF VARIANT MHS1 TRP-328.
RX PubMed=12883402; DOI=10.1097/00000542-200308000-00011;
RA Loke J.C.P., Kraev N., Sharma P., Du G., Patel L., Kraev A.,
RA MacLennan D.H.;
RT "Detection of a novel ryanodine receptor subtype 1 mutation (R328W) in a
RT malignant hyperthermia family by sequencing of a leukocyte transcript.";
RL Anesthesiology 99:297-302(2003).
RN [51]
RP VARIANTS CCD HIS-4861; CYS-4864; TRP-4893 AND THR-4940.
RX PubMed=14670767; DOI=10.1136/adc.88.12.1051;
RA Quinlivan R.M., Muller C.R., Davis M., Laing N.G., Evans G.A., Dwyer J.,
RA Dove J., Roberts A.P., Sewry C.A.;
RT "Central core disease: clinical, pathological, and genetic features.";
RL Arch. Dis. Child. 88:1051-1055(2003).
RN [52]
RP VARIANTS CCD GLU-215; CYS-614; PRO-4650; GLN-4724 AND GLU-4899.
RX PubMed=12937085; DOI=10.1093/brain/awg244;
RA Romero N.B., Monnier N., Viollet L., Cortey A., Chevallay M., Leroy J.P.,
RA Lunardi J., Fardeau M.;
RT "Dominant and recessive central core disease associated with RYR1 mutations
RT and fetal akinesia.";
RL Brain 126:2341-2349(2003).
RN [53]
RP VARIANTS MHS1 CYS-44; CYS-533; LEU-2117; PRO-2163; MET-2168; LEU-2435 AND
RP HIS-2454, AND VARIANT LYS-2101.
RX PubMed=12709367; DOI=10.1373/49.5.761;
RA Tammaro A., Bracco A., Cozzolino S., Esposito M., Di Martino A., Savoia G.,
RA Zeuli L., Piluso G., Aurino S., Nigro V.;
RT "Scanning for mutations of the ryanodine receptor (RYR1) gene by denaturing
RT HPLC: detection of three novel malignant hyperthermia alleles.";
RL Clin. Chem. 49:761-768(2003).
RN [54]
RP VARIANT CCD 4863-ARG--ASP-4869 DELINS TYR.
RX PubMed=12566385; DOI=10.1093/hmg/ddg032;
RA Zorzato F., Yamaguchi N., Xu L., Meissner G., Mueller C.R., Pouliquin P.,
RA Muntoni F., Sewry C., Girard T., Treves S.;
RT "Clinical and functional effects of a deletion in a COOH-terminal lumenal
RT loop of the skeletal muscle ryanodine receptor.";
RL Hum. Mol. Genet. 12:379-388(2003).
RN [55]
RP INVOLVEMENT IN MMDO.
RX PubMed=12719381; DOI=10.1093/hmg/ddg121;
RA Monnier N., Ferreiro A., Marty I., Labarre-Vila A., Mezin P., Lunardi J.;
RT "A homozygous splicing mutation causing a depletion of skeletal muscle RYR1
RT is associated with multi-minicore disease congenital myopathy with
RT ophthalmoplegia.";
RL Hum. Mol. Genet. 12:1171-1178(2003).
RN [56]
RP VARIANT CORE/ROD DISEASE ILE-4637, AND VARIANTS CCD ASP-4638; PRO-4651;
RP CYS-4861; HIS-4861; GLN-4893; THR-4898; GLY-4914; THR-4914;
RP 4927-VAL-ILE-4928 DEL AND THR-4940.
RX PubMed=12565913; DOI=10.1016/s0960-8966(02)00218-3;
RA Davis M.R., Haan E., Jungbluth H., Sewry C., North K., Muntoni F.,
RA Kuntzer T., Lamont P., Bankier A., Tomlinson P., Sanchez A., Walsh P.,
RA Nagarajan L., Oley C., Colley A., Gedeon A., Quinlivan R., Dixon J.,
RA James D., Mueller C.R., Laing N.G.;
RT "Principal mutation hotspot for central core disease and related myopathies
RT in the C-terminal transmembrane region of the RYR1 gene.";
RL Neuromuscul. Disord. 13:151-157(2003).
RN [57]
RP VARIANTS MHS1 CYS-163; ARG-248; CYS-614; CYS-2163; MET-2168; MET-2206;
RP ILE-2214; THR-2350; THR-2367; ASN-2431; ARG-2434; VAL-2437; HIS-2454 AND
RP PRO-4824.
RX PubMed=15448513; DOI=10.1097/00000542-200410000-00005;
RA Sei Y., Sambuughin N.N., Davis E.J., Sachs D., Cuenca P.B., Brandom B.W.,
RA Tautz T., Rosenberg H., Nelson T.E., Muldoon S.M.;
RT "Malignant hyperthermia in North America: genetic screening of the three
RT hot spots in the type I ryanodine receptor gene.";
RL Anesthesiology 101:824-830(2004).
RN [58]
RP VARIANTS TRP-2676 AND SER-2787.
RX PubMed=14732627; DOI=10.1001/archneur.61.1.106;
RA Guis S., Figarella-Branger D., Monnier N., Bendahan D., Kozak-Ribbens G.,
RA Mattei J.-P., Lunardi J., Cozzone P.J., Pellissier J.-F.;
RT "Multiminicore disease in a family susceptible to malignant hyperthermia:
RT histology, in vitro contracture tests, and genetic characterization.";
RL Arch. Neurol. 61:106-113(2004).
RN [59]
RP VARIANTS CCD GLY-160; ASP-4638; PHE-4814; HIS-4861 AND MET-4938, AND
RP VARIANTS MHS1 CYS-614; MET-2346; GLY-2348; TRP-2452; HIS-2458; PRO-4824 AND
RP GLU-4939.
RX PubMed=14985404; DOI=10.1136/jmg.2003.014274;
RA Shepherd S., Ellis F., Halsall J., Hopkins P., Robinson R.;
RT "RYR1 mutations in UK central core disease patients: more than just the C-
RT terminal transmembrane region of the RYR1 gene.";
RL J. Med. Genet. 41:E33-E33(2004).
RN [60]
RP VARIANT MHS1 SER-2342.
RX PubMed=15221887; DOI=10.1002/mus.20068;
RA Marchant C.L., Ellis F.R., Halsall P.J., Hopkins P.M., Robinson R.L.;
RT "Mutation analysis of two patients with hypokalemic periodic paralysis and
RT suspected malignant hyperthermia.";
RL Muscle Nerve 30:114-117(2004).
RN [61]
RP VARIANTS MHS1 ARG-35; CYS-163; LEU-163; ARG-165; ASN-166; CYS-177; CYS-178;
RP VAL-227; ARG-248; TRP-328; ARG-341; SER-401; HIS-401; MET-403; SER-522;
RP TRP-552; CYS-614; LEU-614; CYS-2163; HIS-2163; MET-2168; MET-2206;
RP ARG-2206; ASP-2344; MET-2346; THR-2350; THR-2428; ARG-2434; HIS-2435;
RP CYS-2454; HIS-2454; CYS-2458; MET-3916; SER-4684; GLN-4737; TRP-4737;
RP ILE-4826; VAL-4838; ILE-4849; ARG-4876; GLU-4939 AND LEU-4973, VARIANTS
RP TRP-2676 AND SER-2787, CHARACTERIZATION OF VARIANTS MHS1 LEU-163; MET-2206;
RP THR-2428; CYS-2454 AND HIS-2454, FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=16163667; DOI=10.1002/humu.20231;
RA Monnier N., Kozak-Ribbens G., Krivosic-Horber R., Nivoche Y., Qi D.,
RA Kraev N., Loke J., Sharma P., Tegazzin V., Figarella-Branger D., Romero N.,
RA Mezin P., Bendahan D., Payen J.-F., Depret T., Maclennan D.H., Lunardi J.;
RT "Correlations between genotype and pharmacological, histological,
RT functional, and clinical phenotypes in malignant hyperthermia
RT susceptibility.";
RL Hum. Mutat. 26:413-425(2005).
RN [62]
RP VARIANTS MMDO TRP-109 AND LYS-2423, AND VARIANTS VAL-485 AND CYS-2060.
RX PubMed=16380615; DOI=10.1212/01.wnl.0000188870.37076.f2;
RA Jungbluth H., Zhou H., Hartley L., Halliger-Keller B., Messina S.,
RA Longman C., Brockington M., Robb S.A., Straub V., Voit T., Swash M.,
RA Ferreiro A., Bydder G., Sewry C.A., Mueller C., Muntoni F.;
RT "Minicore myopathy with ophthalmoplegia caused by mutations in the
RT ryanodine receptor type 1 gene.";
RL Neurology 65:1930-1935(2005).
RN [63]
RP VARIANT CCD VAL-4846.
RX PubMed=17204054; DOI=10.1111/j.1399-0004.2006.00725.x;
RA Gambelli S., Malandrini A., Berti G., Gaudiano C., Zicari E., Brunori P.,
RA Perticoni G., Orrico A., Galli L., Sorrentino V., Lunardi J., Federico A.,
RA Dotti M.T.;
RT "Inheritance of a novel RYR1 mutation in a family with myotonic dystrophy
RT type 1.";
RL Clin. Genet. 71:93-94(2007).
RN [64]
RP VARIANTS CCD GLN-4558; VAL-4846; ILE-4849; HIS-4861; CYS-4861; VAL-4897 AND
RP THR-4914.
RX PubMed=17226826; DOI=10.1002/mus.20715;
RA Kossugue P.M., Paim J.F., Navarro M.M., Silva H.C., Pavanello R.C.M.,
RA Gurgel-Giannetti J., Zatz M., Vainzof M.;
RT "Central core disease due to recessive mutations in RYR1 gene: is it more
RT common than described?";
RL Muscle Nerve 35:670-674(2007).
RN [65]
RP VARIANT CCD MET-4882.
RX PubMed=18312400; DOI=10.1111/j.1468-1331.2008.02094.x;
RA von der Hagen M., Kress W., Hahn G., Brocke K.S., Mitzscherling P.,
RA Huebner A., Muller-Reible C., Stoltenburg-Didinger G., Kaindl A.M.;
RT "Novel RYR1 missense mutation causes core rod myopathy.";
RL Eur. J. Neurol. 15:E31-E32(2008).
RN [66]
RP VARIANTS CCD VAL-13; SER-1704; PRO-2421; LYS-2423; HIS-3539; GLN-3772;
RP GLN-4558; MET-4842 AND ILE-4849.
RX PubMed=18253926; DOI=10.1002/humu.20696;
RA Monnier N., Marty I., Faure J., Castiglioni C., Desnuelle C., Sacconi S.,
RA Estournet B., Ferreiro A., Romero N., Laquerriere A., Lazaro L.,
RA Martin J.-J., Morava E., Rossi A., Van der Kooi A., de Visser M.,
RA Verschuuren C., Lunardi J.;
RT "Null mutations causing depletion of the type 1 ryanodine receptor (RYR1)
RT are commonly associated with recessive structural congenital myopathies
RT with cores.";
RL Hum. Mutat. 29:670-678(2008).
RN [67]
RP VARIANTS MHS1 ARG-13; LYS-226; LEU-367; HIS-530; TYR-544; CYS-1043;
RP HIS-2336; LYS-2404; GLY-2730; LYS-2880; PRO-3217; LYS-3290; TRP-3772;
RP ARG-3806; VAL-4838; ARG-4876 AND THR-4938, AND VARIANTS GLY-1342; GLY-1352;
RP LEU-1787; ALA-1832; CYS-2060; VAL-2321; VAL-2550; TRP-2676; SER-2787;
RP GLN-3583; GLU-3756 AND LEU-4501.
RX PubMed=19191329; DOI=10.1002/humu.20878;
RA Levano S., Vukcevic M., Singer M., Matter A., Treves S., Urwyler A.,
RA Girard T.;
RT "Increasing the number of diagnostic mutations in malignant hyperthermia.";
RL Hum. Mutat. 30:590-598(2009).
RN [68]
RP VARIANT MHS1 CYS-2508.
RX PubMed=19685112; DOI=10.1007/s00540-009-0746-3;
RA Migita T., Mukaida K., Hamada H., Yasuda T., Haraki T., Nishino I.,
RA Murakami N., Kawamoto M.;
RT "Functional analysis of ryanodine receptor type 1 p.R2508C mutation in exon
RT 47.";
RL J. Anesth. 23:341-346(2009).
RN [69]
RP VARIANTS MHS1 ASN-382; LYS-1058 AND ARG-1393, VARIANT CCD GLY-2508, AND
RP VARIANT HIS-1679.
RX PubMed=20142353; DOI=10.1213/ane.0b013e3181cbd815;
RA Vukcevic M., Broman M., Islander G., Bodelsson M., Ranklev-Twetman E.,
RA Muller C.R., Treves S.;
RT "Functional properties of RYR1 mutations identified in Swedish patients
RT with malignant hyperthermia and central core disease.";
RL Anesth. Analg. 111:185-190(2010).
RN [70]
RP VARIANTS MMDO THR-402; LEU-2035; LYS-3326 AND GLY-3402.
RX PubMed=20583297; DOI=10.1002/humu.21278;
RA Clarke N.F., Waddell L.B., Cooper S.T., Perry M., Smith R.L.L.,
RA Kornberg A.J., Muntoni F., Lillis S., Straub V., Bushby K., Guglieri M.,
RA King M.D., Farrell M.A., Marty I., Lunardi J., Monnier N., North K.N.;
RT "Recessive mutations in RYR1 are a common cause of congenital fiber type
RT disproportion.";
RL Hum. Mutat. 31:E1544-E1550(2010).
RN [71]
RP VARIANTS MHS1 ASN-1056; HIS-1127; ARG-1467; VAL-1571; GLN-2013; GLY-2400;
RP GLY-2593; GLN-3410; TYR-3501 AND CYS-3933, AND VARIANTS LYS-899; CYS-2060;
RP CYS-2248; TYR-2976 AND GLN-3360.
RX PubMed=20681998; DOI=10.1111/j.1399-0004.2010.01493.x;
RA Tammaro A., Di Martino A., Bracco A., Cozzolino S., Savoia G., Andria B.,
RA Cannavo A., Spagnuolo M., Piluso G., Aurino S., Nigro V.;
RT "Novel missense mutations and unexpected multiple changes of RYR1 gene in
RT 75 malignant hyperthermia families.";
RL Clin. Genet. 79:438-447(2011).
RN [72]
RP VARIANTS CCD GLY-160; GLN-2204; HIS-3366; CYS-3933 AND ASP-4743, AND
RP VARIANTS LEU-1787; CYS-2060 AND ALA-4493.
RX PubMed=21674524; DOI=10.1002/mus.22009;
RA Duarte S.T., Oliveira J., Santos R., Pereira P., Barroso C., Conceicao I.,
RA Evangelista T.;
RT "Dominant and recessive RYR1 mutations in adults with core lesions and mild
RT muscle symptoms.";
RL Muscle Nerve 44:102-108(2011).
RN [73]
RP VARIANTS MHS1 HIS-1056; MET-2627 AND LEU-4234.
RX PubMed=24013571; DOI=10.1097/aln.0b013e3182a8a998;
RA Kim J.H., Jarvik G.P., Browning B.L., Rajagopalan R., Gordon A.S.,
RA Rieder M.J., Robertson P.D., Nickerson D.A., Fisher N.A., Hopkins P.M.;
RT "Exome sequencing reveals novel rare variants in the ryanodine receptor and
RT calcium channel genes in malignant hyperthermia families.";
RL Anesthesiology 119:1054-1065(2013).
RN [74]
RP VARIANTS MHS1 ALA-40; CYS-163; ARG-248; ARG-341; PRO-487; ALA-518; CYS-614;
RP HIS-1043; HIS-2163; MET-2206; HIS-2248; HIS-2351; MET-2354; LEU-2358;
RP GLN-2383; ARG-2434; HIS-2454; ARG-3711; VAL-4178; ARG-4230; GLU-4837;
RP HIS-4861 AND GLY-4906, VARIANTS CCD TRP-975; MET-2168 AND GLY-3238, AND
RP VARIANTS MET-974; LEU-1109; ARG-1393; LEU-1787; CYS-2060 AND VAL-2321.
RX PubMed=23558838; DOI=10.1213/ane.0b013e31828a71ff;
RA Brandom B.W., Bina S., Wong C.A., Wallace T., Visoiu M., Isackson P.J.,
RA Vladutiu G.D., Sambuughin N., Muldoon S.M.;
RT "Ryanodine receptor type 1 gene variants in the malignant hyperthermia-
RT susceptible population of the United States.";
RL Anesth. Analg. 116:1078-1086(2013).
RN [75]
RP VARIANTS CCD HIS-4861; ALA-4897 AND THR-4898.
RX PubMed=24561095; DOI=10.1016/j.neulet.2014.02.015;
RA Gu M., Zhang S., Hu J., Yuan Y., Wang Z., Da Y., Wu S.;
RT "Novel RYR1 missense mutations in six Chinese patients with central core
RT disease.";
RL Neurosci. Lett. 566:32-35(2014).
RN [76]
RP CHARACTERIZATION OF VARIANT CCD GLY-2508, CHARACTERIZATION OF VARIANT MHS1
RP HIS-2508, AND MUTAGENESIS OF ARG-2508.
RX PubMed=26381711; DOI=10.1213/ane.0000000000000886;
RA Miyoshi H., Yasuda T., Otsuki S., Kondo T., Haraki T., Mukaida K.,
RA Nakamura R., Hamada H., Kawamoto M.;
RT "Several ryanodine receptor type 1 gene mutations of p.Arg2508 are
RT potential sources of malignant hyperthermia.";
RL Anesth. Analg. 121:994-1000(2015).
RN [77]
RP CHARACTERIZATION OF VARIANTS MHS1 ARG-35; CYS-163; LEU-163; ARG-248;
RP ARG-341; CYS-401; HIS-401; SER-522; CYS-614 AND LEU-614, AND MUTAGENESIS OF
RP TYR-522.
RX PubMed=26115329; DOI=10.1371/journal.pone.0130606;
RA Murayama T., Kurebayashi N., Yamazawa T., Oyamada H., Suzuki J.,
RA Kanemaru K., Oguchi K., Iino M., Sakurai T.;
RT "Divergent activity profiles of type 1 ryanodine receptor channels carrying
RT malignant hyperthermia and central core disease mutations in the amino-
RT terminal Region.";
RL PLoS ONE 10:E0130606-E0130606(2015).
RN [78]
RP CHARACTERIZATION OF VARIANTS MHS1 CYS-2163; HIS-2163; MET-2168; MET-2206;
RP THR-2350; ARG-2434; HIS-2435; CYS-2454; HIS-2454; CYS-2458; HIS-2458 AND
RP HIS-2508, CHARACTERIZATION OF VARIANT CCD CYS-2508, AND CHARACTERIZATION OF
RP VARIANT ALA-2375 AND HIS-2508.
RX PubMed=27586648; DOI=10.1002/humu.23072;
RA Murayama T., Kurebayashi N., Ogawa H., Yamazawa T., Oyamada H., Suzuki J.,
RA Kanemaru K., Oguchi K., Iino M., Sakurai T.;
RT "Genotype-phenotype correlations of malignant hyperthermia and central core
RT disease mutations in the central region of the RYR1 channel.";
RL Hum. Mutat. 37:1231-1241(2016).
RN [79]
RP VARIANT MHS1 TRP-4737, AND CHARACTERIZATION OF VARIANT MHS1 TRP-4737.
RX PubMed=26631338; DOI=10.1016/j.nmd.2015.11.001;
RA Johannsen S., Treves S., Mueller C.R., Moegele S., Schneiderbanger D.,
RA Roewer N., Schuster F.;
RT "Functional characterization of the RYR1 mutation p.Arg4737Trp associated
RT with susceptibility to malignant hyperthermia.";
RL Neuromuscul. Disord. 26:21-25(2016).
RN [80]
RP VARIANT ARG-705.
RX PubMed=27616680; DOI=10.1002/pd.4925;
RA Casey J., Flood K., Ennis S., Doyle E., Farrell M., Lynch S.A.;
RT "Intra-familial variability associated with recessive RYR1 mutation
RT diagnosed prenatally by exome sequencing.";
RL Prenat. Diagn. 36:1020-1026(2016).
RN [81]
RP VARIANTS CCD PRO-2963 AND ASP-4806.
RX PubMed=27234031; DOI=10.1111/cge.12810;
RA Fattahi Z., Kalhor Z., Fadaee M., Vazehan R., Parsimehr E., Abolhassani A.,
RA Beheshtian M., Zamani G., Nafissi S., Nilipour Y., Akbari M.R., Kahrizi K.,
RA Kariminejad A., Najmabadi H.;
RT "Improved diagnostic yield of neuromuscular disorders applying clinical
RT exome sequencing in patients arising from a consanguineous population.";
RL Clin. Genet. 91:386-402(2017).
CC -!- FUNCTION: Calcium channel that mediates the release of Ca(2+) from the
CC sarcoplasmic reticulum into the cytoplasm and thereby plays a key role
CC in triggering muscle contraction following depolarization of T-tubules
CC (PubMed:11741831, PubMed:16163667). Repeated very high-level exercise
CC increases the open probability of the channel and leads to Ca(2+)
CC leaking into the cytoplasm (PubMed:18268335). Can also mediate the
CC release of Ca(2+) from intracellular stores in neurons, and may thereby
CC promote prolonged Ca(2+) signaling in the brain. Required for normal
CC embryonic development of muscle fibers and skeletal muscle. Required
CC for normal heart morphogenesis, skin development and ossification
CC during embryogenesis (By similarity). {ECO:0000250|UniProtKB:E9PZQ0,
CC ECO:0000269|PubMed:18268335, ECO:0000305|PubMed:11741831,
CC ECO:0000305|PubMed:16163667}.
CC -!- ACTIVITY REGULATION: Channel activity is modulated by the alkaloid
CC ryanodine that binds to the open Ca-release channel with high affinity.
CC At low concentrations, ryanodine maintains the channel in an open
CC conformation. High ryanodine concentrations inhibit channel activity
CC (By similarity). Channel activity is regulated by calmodulin (CALM)
CC (PubMed:18650434). The calcium release is activated by increased
CC cytoplasmic calcium levels, by nitric oxyde (NO), caffeine and ATP
CC (PubMed:18268335, PubMed:16163667). Channel activity is inhibited by
CC magnesium ions, possibly by competition for calcium binding sites (By
CC similarity). {ECO:0000250|UniProtKB:P11716,
CC ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:18268335,
CC ECO:0000269|PubMed:18650434}.
CC -!- SUBUNIT: Homotetramer. Can also form heterotetramers with RYR2 (By
CC similarity). Identified in a complex composed of RYR1, PDE4D, PKA,
CC FKBP1A and protein phosphatase 1 (PP1) (PubMed:18268335). Repeated very
CC high-level exercise decreases interaction with PDE4D and protein
CC phosphatase 1 (PP1) (PubMed:18268335). Interacts with CALM; CALM with
CC bound calcium inhibits the RYR1 channel activity (PubMed:18650434).
CC Interacts with S100A1 (PubMed:18650434). Interacts with FKBP1A; this
CC stabilizes the closed conformation of the channel. Interacts with
CC CACNA1S; interaction with CACNA1S is important for activation of the
CC RYR1 channel. Interacts with CACNB1. Interacts with TRDN and ASPH;
CC these interactions stimulate RYR1 channel activity. Interacts with
CC SELENON (By similarity). Interacts with scorpion calcins (AC P0DPT1; AC
CC P0DM30; AC A0A1L4BJ42; AC P59868; AC P60254; AC B8QG00; AC L0GBR1; AC
CC P60252; AC P60253) (By similarity). {ECO:0000250|UniProtKB:E9PZQ0,
CC ECO:0000250|UniProtKB:P11716, ECO:0000269|PubMed:18268335,
CC ECO:0000269|PubMed:18650434}.
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane
CC {ECO:0000269|PubMed:7556644}; Multi-pass membrane protein
CC {ECO:0000305}. Sarcoplasmic reticulum {ECO:0000250|UniProtKB:P11716}.
CC Note=The number of predicted transmembrane domains varies between
CC orthologs, but the 3D-structures show the presence of six transmembrane
CC regions. Both N-terminus and C-terminus are cytoplasmic.
CC {ECO:0000250|UniProtKB:P11716}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1;
CC IsoId=P21817-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P21817-2; Sequence=VSP_005951;
CC Name=3;
CC IsoId=P21817-3; Sequence=VSP_005952;
CC -!- TISSUE SPECIFICITY: Skeletal muscle and brain (cerebellum and
CC hippocampus). {ECO:0000269|PubMed:9607712}.
CC -!- DOMAIN: The calcium release channel activity resides in the C-terminal
CC region while the remaining part of the protein constitutes the 'foot'
CC structure spanning the junctional gap between the sarcoplasmic
CC reticulum (SR) and the T-tubule. Pore opening is mediated via the
CC cytoplasmic calcium-binding domains that mediate a small rotation of
CC the channel-forming transmembrane regions that then leads to channel
CC opening. {ECO:0000250|UniProtKB:P11716}.
CC -!- PTM: Channel activity is modulated by phosphorylation. Phosphorylation
CC at Ser-2843 may increase channel activity. Repeated very high-level
CC exercise increases phosphorylation at Ser-2843.
CC {ECO:0000269|PubMed:18268335}.
CC -!- PTM: Activated by reversible S-nitrosylation (By similarity). Repeated
CC very high-level exercise increases S-nitrosylation (PubMed:18268335).
CC {ECO:0000250|UniProtKB:P11716, ECO:0000269|PubMed:18268335}.
CC -!- DISEASE: Malignant hyperthermia 1 (MHS1) [MIM:145600]: Autosomal
CC dominant pharmacogenetic disorder of skeletal muscle and is one of the
CC main causes of death due to anesthesia. In susceptible people, an MH
CC episode can be triggered by all commonly used inhalational anesthetics
CC such as halothane and by depolarizing muscle relaxants such as
CC succinylcholine. The clinical features of the myopathy are
CC hyperthermia, accelerated muscle metabolism, contractures, metabolic
CC acidosis, tachycardia and death, if not treated with the postsynaptic
CC muscle relaxant, dantrolene. Susceptibility to MH can be determined
CC with the 'in vitro' contracture test (IVCT): observing the magnitude of
CC contractures induced in strips of muscle tissue by caffeine alone and
CC halothane alone. Patients with normal response are MH normal (MHN),
CC those with abnormal response to caffeine alone or halothane alone are
CC MH equivocal (MHE(C) and MHE(H) respectively).
CC {ECO:0000269|PubMed:10051009, ECO:0000269|PubMed:10484775,
CC ECO:0000269|PubMed:10612851, ECO:0000269|PubMed:10823104,
CC ECO:0000269|PubMed:10888602, ECO:0000269|PubMed:11241852,
CC ECO:0000269|PubMed:11389482, ECO:0000269|PubMed:11525881,
CC ECO:0000269|PubMed:11575529, ECO:0000269|PubMed:11928716,
CC ECO:0000269|PubMed:12059893, ECO:0000269|PubMed:12066726,
CC ECO:0000269|PubMed:12123492, ECO:0000269|PubMed:12208234,
CC ECO:0000269|PubMed:12411788, ECO:0000269|PubMed:12709367,
CC ECO:0000269|PubMed:12883402, ECO:0000269|PubMed:1354642,
CC ECO:0000269|PubMed:14732627, ECO:0000269|PubMed:14985404,
CC ECO:0000269|PubMed:15221887, ECO:0000269|PubMed:15448513,
CC ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:1774074,
CC ECO:0000269|PubMed:19191329, ECO:0000269|PubMed:19685112,
CC ECO:0000269|PubMed:20142353, ECO:0000269|PubMed:20681998,
CC ECO:0000269|PubMed:23558838, ECO:0000269|PubMed:24013571,
CC ECO:0000269|PubMed:26115329, ECO:0000269|PubMed:26381711,
CC ECO:0000269|PubMed:26631338, ECO:0000269|PubMed:27586648,
CC ECO:0000269|PubMed:7751854, ECO:0000269|PubMed:7849712,
CC ECO:0000269|PubMed:7881417, ECO:0000269|PubMed:8012359,
CC ECO:0000269|PubMed:8220423, ECO:0000269|PubMed:9066328,
CC ECO:0000269|PubMed:9138151, ECO:0000269|PubMed:9389851,
CC ECO:0000269|PubMed:9450902, ECO:0000269|PubMed:9497245}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- DISEASE: Central core disease of muscle (CCD) [MIM:117000]: Autosomal
CC dominant congenital myopathy, but a severe autosomal recessive form
CC also exists. Both clinical and histological variability is observed.
CC Affected individuals typically display hypotonia and proximal muscle
CC weakness in infancy, leading to the delay of motor milestones. The
CC clinical course of the disorder is usually slow or nonprogressive in
CC adulthood, and the severity of the symptoms may vary from normal to
CC significant muscle weakness. Microscopic examination of CCD-affected
CC skeletal muscle reveals a predominance of type I fibers containing
CC amorphous-looking areas (cores) that do not stain with oxidative and
CC phosphorylase histochemical techniques. {ECO:0000269|PubMed:10097181,
CC ECO:0000269|PubMed:11113224, ECO:0000269|PubMed:11709545,
CC ECO:0000269|PubMed:11741831, ECO:0000269|PubMed:12112081,
CC ECO:0000269|PubMed:12136074, ECO:0000269|PubMed:12565913,
CC ECO:0000269|PubMed:12566385, ECO:0000269|PubMed:12937085,
CC ECO:0000269|PubMed:14670767, ECO:0000269|PubMed:14985404,
CC ECO:0000269|PubMed:17204054, ECO:0000269|PubMed:17226826,
CC ECO:0000269|PubMed:18253926, ECO:0000269|PubMed:18312400,
CC ECO:0000269|PubMed:20142353, ECO:0000269|PubMed:21674524,
CC ECO:0000269|PubMed:23558838, ECO:0000269|PubMed:24561095,
CC ECO:0000269|PubMed:26381711, ECO:0000269|PubMed:27234031,
CC ECO:0000269|PubMed:27586648, ECO:0000269|PubMed:7829078,
CC ECO:0000269|PubMed:8220422, ECO:0000269|PubMed:8220423,
CC ECO:0000269|PubMed:9497245}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Multiminicore disease with external ophthalmoplegia (MMDO)
CC [MIM:255320]: Clinically heterogeneous neuromuscular disorder. General
CC features include neonatal hypotonia, delayed motor development, and
CC generalized muscle weakness and amyotrophy, which may progress slowly
CC or remain stable. Muscle biopsy shows multiple, poorly circumscribed,
CC short areas of sarcomere disorganization and mitochondria depletion
CC (areas termed minicores) in most muscle fibers. Typically, no
CC dystrophic signs, such as muscle fiber necrosis or regeneration or
CC significant endomysial fibrosis, are present in multiminicore disease.
CC {ECO:0000269|PubMed:12719381, ECO:0000269|PubMed:16380615,
CC ECO:0000269|PubMed:20583297}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Defects in RYR1 may be a cause of Samaritan myopathy, a
CC congenital myopathy with benign course. Patients display severe
CC hypotonia and respiratory distress at birth. Unlike other congenital
CC myopathies, the health status constantly improves and patients are
CC minimally affected at adulthood.
CC -!- DISEASE: King-Denborough syndrome (KDS) [MIM:619542]: An autosomal
CC dominant disorder characterized by the triad of dysmorphic features,
CC congenital myopathy, and susceptibility to malignant hyperthermia.
CC Variable expressivity has been reported in several cases.
CC {ECO:0000269|PubMed:18765655, ECO:0000269|PubMed:21514828,
CC ECO:0000269|PubMed:27918309}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Coexpression of normal and mutant Thr-4898 RYR1 in a 1:1
CC ratio produces RYR1 channels with normal halothane and caffeine
CC sensitivities, but maximal levels of Ca(2+) release are reduced by 67%.
CC Binding of [3H]ryanodine indicates that the heterozygous channel is
CC activated by Ca(2+) concentrations 4-fold lower than normal. Single-
CC cell analysis of cotransfected cells shows a significantly increased
CC resting cytoplasmic Ca(2+) level and a significantly reduced luminal
CC Ca(2+) level. These data indicated a leaky channel, possibly caused by
CC a reduction in the Ca(2+) concentration required for channel
CC activation. Comparison with 2 other coexpressed mutant/normal channels
CC suggests that the Thr-4898 mutation produces one of the most abnormal
CC RYR1 channels that has been investigated, and this level of abnormality
CC is reflected in the severe and penetrant phenotype of affected CCD
CC individuals. {ECO:0000269|PubMed:10097181}.
CC -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR1
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ryanodine receptor entry;
CC URL="https://en.wikipedia.org/wiki/Ryanodine_receptor";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=RYR1 entry;
CC URL="https://databases.lovd.nl/shared/genes//RYR1";
CC -!- WEB RESOURCE: Name=Leiden Muscular Dystrophy pages Ryanodine receptor 1
CC (skeletal) (RYR1); Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/RYR1";
CC ---------------------------------------------------------------------------
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DR EMBL; J05200; AAA60294.1; -; mRNA.
DR EMBL; U48508; AAC51191.1; -; Genomic_DNA.
DR EMBL; U48449; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48450; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48451; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48452; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48453; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48454; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48455; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48456; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48457; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48458; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48459; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48460; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48461; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48462; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48463; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48464; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48465; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48466; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48467; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48468; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48469; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48470; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48471; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48472; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48473; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48474; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48475; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48476; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48477; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48478; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48479; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48480; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48481; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48482; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48483; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48484; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48485; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48486; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48487; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48488; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48489; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48490; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48491; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48492; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48493; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48494; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48495; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48496; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48497; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48498; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48499; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48500; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48501; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48502; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48503; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48504; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48505; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48506; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; U48507; AAC51191.1; JOINED; Genomic_DNA.
DR EMBL; AC067969; AAF66076.1; -; Genomic_DNA.
DR EMBL; AC005933; AAC71651.1; -; Genomic_DNA.
DR EMBL; AC011469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M91455; AAA60295.1; -; Genomic_DNA.
DR EMBL; S78717; AAB21245.2; -; Genomic_DNA.
DR EMBL; S77392; AAB34356.1; -; Genomic_DNA.
DR CCDS; CCDS33011.1; -. [P21817-1]
DR CCDS; CCDS42563.1; -. [P21817-2]
DR PIR; A35041; A35041.
DR RefSeq; NP_000531.2; NM_000540.2. [P21817-1]
DR RefSeq; NP_001036188.1; NM_001042723.1. [P21817-2]
DR PDB; 6UHI; X-ray; 2.88 A; A=849-962.
DR PDB; 6UHS; X-ray; 2.46 A; A=849-962.
DR PDBsum; 6UHI; -.
DR PDBsum; 6UHS; -.
DR SMR; P21817; -.
DR BioGRID; 112173; 25.
DR ComplexPortal; CPX-3135; Ryanodine 1 complex.
DR DIP; DIP-29708N; -.
DR ELM; P21817; -.
DR IntAct; P21817; 14.
DR MINT; P21817; -.
DR STRING; 9606.ENSP00000352608; -.
DR BindingDB; P21817; -.
DR ChEMBL; CHEMBL1846; -.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR DrugBank; DB01219; Dantrolene.
DR DrugBank; DB04786; Suramin.
DR DrugBank; DB09085; Tetracaine.
DR DrugCentral; P21817; -.
DR TCDB; 1.A.3.1.2; the ryanodine-inositol 1,4,5-triphosphate receptor ca(2+) channel (rir-cac) family.
DR CarbonylDB; P21817; -.
DR GlyGen; P21817; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P21817; -.
DR PhosphoSitePlus; P21817; -.
DR BioMuta; RYR1; -.
DR DMDM; 108935904; -.
DR EPD; P21817; -.
DR jPOST; P21817; -.
DR MassIVE; P21817; -.
DR PaxDb; P21817; -.
DR PeptideAtlas; P21817; -.
DR PRIDE; P21817; -.
DR ProteomicsDB; 53930; -. [P21817-1]
DR ProteomicsDB; 53931; -. [P21817-2]
DR ProteomicsDB; 53932; -. [P21817-3]
DR Antibodypedia; 44914; 174 antibodies from 24 providers.
DR DNASU; 6261; -.
DR Ensembl; ENST00000355481.8; ENSP00000347667.3; ENSG00000196218.14. [P21817-2]
DR Ensembl; ENST00000359596.8; ENSP00000352608.2; ENSG00000196218.14. [P21817-1]
DR GeneID; 6261; -.
DR KEGG; hsa:6261; -.
DR MANE-Select; ENST00000359596.8; ENSP00000352608.2; NM_000540.3; NP_000531.2.
DR UCSC; uc002oit.4; human. [P21817-1]
DR CTD; 6261; -.
DR DisGeNET; 6261; -.
DR GeneCards; RYR1; -.
DR GeneReviews; RYR1; -.
DR HGNC; HGNC:10483; RYR1.
DR HPA; ENSG00000196218; Tissue enriched (skeletal).
DR MalaCards; RYR1; -.
DR MIM; 117000; phenotype.
DR MIM; 145600; phenotype.
DR MIM; 180901; gene.
DR MIM; 255320; phenotype.
DR MIM; 619542; phenotype.
DR neXtProt; NX_P21817; -.
DR OpenTargets; ENSG00000196218; -.
DR Orphanet; 169189; Autosomal dominant centronuclear myopathy.
DR Orphanet; 169186; Autosomal recessive centronuclear myopathy.
DR Orphanet; 324581; Benign Samaritan congenital myopathy.
DR Orphanet; 597; Central core disease.
DR Orphanet; 98905; Congenital multicore myopathy with external ophthalmoplegia.
DR Orphanet; 424107; Congenital myopathy with myasthenic-like onset.
DR Orphanet; 466650; Exercise-induced malignant hyperthermia.
DR Orphanet; 99741; King-Denborough syndrome.
DR Orphanet; 33108; Lethal multiple pterygium syndrome.
DR Orphanet; 423; Malignant hyperthermia of anesthesia.
DR Orphanet; 178145; Moderate multiminicore disease with hand involvement.
DR PharmGKB; PA34896; -.
DR VEuPathDB; HostDB:ENSG00000196218; -.
DR eggNOG; KOG2243; Eukaryota.
DR GeneTree; ENSGT00940000155288; -.
DR HOGENOM; CLU_000040_2_0_1; -.
DR InParanoid; P21817; -.
DR OMA; VMMDDLQ; -.
DR OrthoDB; 5161at2759; -.
DR PhylomeDB; P21817; -.
DR TreeFam; TF315244; -.
DR PathwayCommons; P21817; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR SignaLink; P21817; -.
DR SIGNOR; P21817; -.
DR BioGRID-ORCS; 6261; 16 hits in 1073 CRISPR screens.
DR ChiTaRS; RYR1; human.
DR GeneWiki; RYR1; -.
DR GenomeRNAi; 6261; -.
DR Pharos; P21817; Tclin.
DR PRO; PR:P21817; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P21817; protein.
DR Bgee; ENSG00000196218; Expressed in gluteal muscle and 139 other tissues.
DR ExpressionAtlas; P21817; baseline and differential.
DR Genevisible; P21817; HS.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031674; C:I band; IDA:UniProtKB.
DR GO; GO:0031301; C:integral component of organelle membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0014701; C:junctional sarcoplasmic reticulum membrane; TAS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:1990425; C:ryanodine receptor complex; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IBA:GO_Central.
DR GO; GO:0016529; C:sarcoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0014802; C:terminal cisterna; ISS:UniProtKB.
DR GO; GO:0030018; C:Z disc; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0005262; F:calcium channel activity; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0048763; F:calcium-induced calcium release activity; IMP:UniProtKB.
DR GO; GO:0015278; F:calcium-release channel activity; TAS:ProtInc.
DR GO; GO:0005516; F:calmodulin binding; ISS:BHF-UCL.
DR GO; GO:0005219; F:ryanodine-sensitive calcium-release channel activity; IDA:CACAO.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISS:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; ISS:BHF-UCL.
DR GO; GO:0071313; P:cellular response to caffeine; IMP:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; ISS:UniProtKB.
DR GO; GO:0043931; P:ossification involved in bone maturation; ISS:UniProtKB.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISS:BHF-UCL.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:UniProtKB.
DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0031000; P:response to caffeine; ISS:BHF-UCL.
DR GO; GO:0001666; P:response to hypoxia; IDA:BHF-UCL.
DR GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB.
DR GO; GO:0043588; P:skin development; ISS:UniProtKB.
DR CDD; cd12877; SPRY1_RyR; 1.
DR CDD; cd12878; SPRY2_RyR; 1.
DR CDD; cd12879; SPRY3_RyR; 1.
DR Gene3D; 2.60.120.920; -; 3.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR014821; Ins145_P3_rcpt.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR036300; MIR_dom_sf.
DR InterPro; IPR016093; MIR_motif.
DR InterPro; IPR013662; RIH_assoc-dom.
DR InterPro; IPR000699; RIH_dom.
DR InterPro; IPR013333; Ryan_recept.
DR InterPro; IPR003032; Ryanodine_rcpt.
DR InterPro; IPR009460; Ryanrecept_TM4-6.
DR InterPro; IPR035910; RyR/IP3R_RIH_dom_sf.
DR InterPro; IPR033215; RyR1.
DR InterPro; IPR035761; SPRY1_RyR.
DR InterPro; IPR035764; SPRY2_RyR.
DR InterPro; IPR035762; SPRY3_RyR.
DR InterPro; IPR003877; SPRY_dom.
DR PANTHER; PTHR13715:SF15; PTHR13715:SF15; 1.
DR Pfam; PF08709; Ins145_P3_rec; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF02815; MIR; 1.
DR Pfam; PF08454; RIH_assoc; 1.
DR Pfam; PF06459; RR_TM4-6; 1.
DR Pfam; PF01365; RYDR_ITPR; 2.
DR Pfam; PF02026; RyR; 4.
DR Pfam; PF00622; SPRY; 3.
DR PRINTS; PR00795; RYANODINER.
DR SMART; SM00472; MIR; 4.
DR SMART; SM00449; SPRY; 3.
DR SUPFAM; SSF100909; SSF100909; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49899; SSF49899; 2.
DR SUPFAM; SSF82109; SSF82109; 2.
DR PROSITE; PS50188; B302_SPRY; 3.
DR PROSITE; PS50919; MIR; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Calcium; Calcium channel;
KW Calcium transport; Calmodulin-binding; Developmental protein;
KW Direct protein sequencing; Disease variant; Ion channel; Ion transport;
KW Ligand-gated ion channel; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; S-nitrosylation;
KW Sarcoplasmic reticulum; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..5038
FT /note="Ryanodine receptor 1"
FT /id="PRO_0000219358"
FT TOPO_DOM 1..4559
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4560..4580
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4581..4641
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4642..4662
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4663..4780
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4781..4803
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4804
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4805..4821
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4822..4836
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4837..4857
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4858..4880
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT INTRAMEM 4881..4900
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4901..4920
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4921..4941
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4942..5038
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT DOMAIN 97..152
FT /note="MIR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 159..204
FT /note="MIR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 210..264
FT /note="MIR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 270..327
FT /note="MIR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 335..392
FT /note="MIR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 581..797
FT /note="B30.2/SPRY 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 841..954
FT /note="1"
FT REPEAT 955..1068
FT /note="2"
FT DOMAIN 1013..1208
FT /note="B30.2/SPRY 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 1344..1359
FT /note="3; truncated"
FT DOMAIN 1356..1570
FT /note="B30.2/SPRY 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 1372..1387
FT /note="4; truncated"
FT REPEAT 2726..2845
FT /note="5"
FT REPEAT 2846..2959
FT /note="6"
FT DOMAIN 4074..4102
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 669..680
FT /note="Interaction with FKBP1A"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT REGION 841..2959
FT /note="6 X approximate repeats"
FT REGION 1307..1385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1867..1923
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2391..2412
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2828..2858
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3478..3501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3614..3643
FT /note="Interaction with CALM"
FT /evidence="ECO:0000269|PubMed:18650434"
FT REGION 4251..4280
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4382..4538
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4589..4621
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 4895..4901
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT COMPBIAS 1370..1385
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1870..1919
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2828..2843
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4485..4501
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4502..4519
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4520..4534
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 3892
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 3966
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 4210..4214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 4717
FT /ligand="caffeine"
FT /ligand_id="ChEBI:CHEBI:27732"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 4955..4960
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 4980..4986
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 5002
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT MOD_RES 1337
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 2345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 2843
FT /note="Phosphoserine; by PKA and PKG"
FT /evidence="ECO:0000250|UniProtKB:E9PZQ0"
FT MOD_RES 3635
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT MOD_RES 4467
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 4471
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 4864
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18318008"
FT MOD_RES 4867
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18318008"
FT VAR_SEQ 3481..3485
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2298749"
FT /id="VSP_005951"
FT VAR_SEQ 3865..3869
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_005952"
FT VARIANT 13
FT /note="L -> R (in MHS1; dbSNP:rs193922744)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058560"
FT VARIANT 13
FT /note="L -> V (in CCD; autosomal recessive form)"
FT /evidence="ECO:0000269|PubMed:18253926"
FT /id="VAR_045694"
FT VARIANT 33
FT /note="K -> E (in KDS; dbSNP:rs193922746)"
FT /evidence="ECO:0000269|PubMed:18765655"
FT /id="VAR_086256"
FT VARIANT 35
FT /note="C -> R (in MHS1; increases calcium-induced calcium
FT release activity; dbSNP:rs193922747)"
FT /evidence="ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:26115329, ECO:0000269|PubMed:9066328"
FT /id="VAR_005589"
FT VARIANT 40
FT /note="G -> A (in MHS1; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071721"
FT VARIANT 44
FT /note="R -> C (in CCD and MHS1; dbSNP:rs193922748)"
FT /evidence="ECO:0000269|PubMed:12709367"
FT /id="VAR_045695"
FT VARIANT 109
FT /note="R -> W (in MMDO; dbSNP:rs118192173)"
FT /evidence="ECO:0000269|PubMed:16380615"
FT /id="VAR_032910"
FT VARIANT 160
FT /note="E -> G (in CCD; dbSNP:rs193922752)"
FT /evidence="ECO:0000269|PubMed:14985404,
FT ECO:0000269|PubMed:21674524"
FT /id="VAR_045696"
FT VARIANT 163
FT /note="R -> C (in CCD and MHS1; 2-3% of the cases;
FT increases calcium-induced calcium release activity;
FT dbSNP:rs118192161)"
FT /evidence="ECO:0000269|PubMed:11575529,
FT ECO:0000269|PubMed:12059893, ECO:0000269|PubMed:12208234,
FT ECO:0000269|PubMed:12411788, ECO:0000269|PubMed:15448513,
FT ECO:0000269|PubMed:23558838, ECO:0000269|PubMed:26115329,
FT ECO:0000269|PubMed:8220423, ECO:0000305|PubMed:16163667"
FT /id="VAR_005590"
FT VARIANT 163
FT /note="R -> L (in MHS1; induces an increase sensitivity to
FT caffeine; increases calcium-induced calcium release
FT activity; dbSNP:rs193922753)"
FT /evidence="ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:26115329"
FT /id="VAR_045697"
FT VARIANT 165
FT /note="G -> R (in MHS1; dbSNP:rs193922754)"
FT /evidence="ECO:0000269|PubMed:16163667"
FT /id="VAR_045698"
FT VARIANT 166
FT /note="D -> N (in MHS1; dbSNP:rs193922755)"
FT /evidence="ECO:0000269|PubMed:12059893,
FT ECO:0000269|PubMed:16163667"
FT /id="VAR_045699"
FT VARIANT 177
FT /note="R -> C (in MHS1; dbSNP:rs193922757)"
FT /evidence="ECO:0000269|PubMed:16163667"
FT /id="VAR_045700"
FT VARIANT 178
FT /note="Y -> C (in MHS1)"
FT /evidence="ECO:0000269|PubMed:16163667"
FT /id="VAR_045701"
FT VARIANT 215
FT /note="G -> E (in CCD; autosomal recessive form;
FT dbSNP:rs118192115)"
FT /evidence="ECO:0000269|PubMed:12937085"
FT /id="VAR_045702"
FT VARIANT 226
FT /note="M -> K (in MHS1; dbSNP:rs112596687)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058561"
FT VARIANT 227
FT /note="D -> V (in MHS1; dbSNP:rs193922760)"
FT /evidence="ECO:0000269|PubMed:16163667"
FT /id="VAR_045703"
FT VARIANT 248
FT /note="G -> R (in MHS1; unknown pathological significance;
FT increases calcium-induced calcium release activity;
FT dbSNP:rs1801086)"
FT /evidence="ECO:0000269|PubMed:11575529,
FT ECO:0000269|PubMed:1354642, ECO:0000269|PubMed:15448513,
FT ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:23558838,
FT ECO:0000269|PubMed:26115329"
FT /id="VAR_005591"
FT VARIANT 291
FT /note="A -> T (in dbSNP:rs2229140)"
FT /id="VAR_051890"
FT VARIANT 328
FT /note="R -> W (in MHS1; has increased sensitivity to both
FT caffeine and halothane; dbSNP:rs193922762)"
FT /evidence="ECO:0000269|PubMed:12883402,
FT ECO:0000269|PubMed:16163667"
FT /id="VAR_045704"
FT VARIANT 341
FT /note="G -> R (in MHS1; 10% of the cases; increases
FT calcium-induced calcium release activity;
FT dbSNP:rs121918592)"
FT /evidence="ECO:0000269|PubMed:12059893,
FT ECO:0000269|PubMed:12411788, ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:23558838, ECO:0000269|PubMed:26115329,
FT ECO:0000269|PubMed:8012359"
FT /id="VAR_005592"
FT VARIANT 367
FT /note="R -> L (in MHS1; dbSNP:rs113332073)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058562"
FT VARIANT 382
FT /note="H -> N (in MHS1)"
FT /evidence="ECO:0000269|PubMed:20142353"
FT /id="VAR_068510"
FT VARIANT 401
FT /note="R -> C (in MHS1; increases calcium-induced calcium
FT release activity; dbSNP:rs193922764)"
FT /evidence="ECO:0000269|PubMed:12066726,
FT ECO:0000269|PubMed:12208234, ECO:0000269|PubMed:26115329"
FT /id="VAR_045705"
FT VARIANT 401
FT /note="R -> H (in MHS1; increases calcium-induced calcium
FT release activity; dbSNP:rs193922766)"
FT /evidence="ECO:0000269|PubMed:12059893,
FT ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:26115329"
FT /id="VAR_045706"
FT VARIANT 401
FT /note="R -> S (in MHS1)"
FT /evidence="ECO:0000269|PubMed:16163667"
FT /id="VAR_045707"
FT VARIANT 402
FT /note="M -> T (in MMDO; dbSNP:rs118192117)"
FT /evidence="ECO:0000269|PubMed:20583297"
FT /id="VAR_063846"
FT VARIANT 403
FT /note="I -> M (in CCD and MHS1; dbSNP:rs118192116)"
FT /evidence="ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:8220423"
FT /id="VAR_005593"
FT VARIANT 471
FT /note="R -> C (in dbSNP:rs1376393998)"
FT /evidence="ECO:0000269|PubMed:1354642"
FT /id="VAR_005594"
FT VARIANT 485
FT /note="M -> V (in dbSNP:rs147723844)"
FT /evidence="ECO:0000269|PubMed:16380615"
FT /id="VAR_032911"
FT VARIANT 487
FT /note="L -> P (in MHS1; unknown pathological significance;
FT dbSNP:rs1008860336)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071722"
FT VARIANT 518
FT /note="V -> A (in MHS1; unknown pathological significance;
FT dbSNP:rs1195513704)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071723"
FT VARIANT 522
FT /note="Y -> S (in CCD and MHS1; increases calcium-induced
FT calcium release activity; dbSNP:rs118192162)"
FT /evidence="ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:26115329, ECO:0000269|PubMed:7829078"
FT /id="VAR_005595"
FT VARIANT 530
FT /note="R -> H (in MHS1; dbSNP:rs111888148)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058563"
FT VARIANT 533
FT /note="R -> C (in MHS1; dbSNP:rs193922768)"
FT /evidence="ECO:0000269|PubMed:12709367"
FT /id="VAR_045708"
FT VARIANT 533
FT /note="R -> H (in MHS1; dbSNP:rs144336148)"
FT /id="VAR_008971"
FT VARIANT 544
FT /note="D -> Y (in MHS1; dbSNP:rs113812662)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058564"
FT VARIANT 552
FT /note="R -> W (in MHS1; dbSNP:rs193922770)"
FT /evidence="ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:9138151"
FT /id="VAR_005596"
FT VARIANT 614
FT /note="R -> C (in CCD and MHS1; 3-5% of the cases;
FT increases calcium-induced calcium release activity;
FT dbSNP:rs118192172)"
FT /evidence="ECO:0000269|PubMed:11575529,
FT ECO:0000269|PubMed:12059893, ECO:0000269|PubMed:12411788,
FT ECO:0000269|PubMed:12937085, ECO:0000269|PubMed:14985404,
FT ECO:0000269|PubMed:15448513, ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:1774074, ECO:0000269|PubMed:23558838,
FT ECO:0000269|PubMed:26115329, ECO:0000269|PubMed:7751854"
FT /id="VAR_005597"
FT VARIANT 614
FT /note="R -> L (in MHS1; increases calcium-induced calcium
FT release activity; dbSNP:rs193922772)"
FT /evidence="ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:26115329, ECO:0000269|PubMed:9389851"
FT /id="VAR_005598"
FT VARIANT 705
FT /note="G -> R (probable disease-associated variant found in
FT primary myopathy causing fetal akinesia and pregnancy loss;
FT dbSNP:rs565825739)"
FT /evidence="ECO:0000269|PubMed:27616680"
FT /id="VAR_078775"
FT VARIANT 899
FT /note="N -> K (in dbSNP:rs201401814)"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071724"
FT VARIANT 974
FT /note="V -> M (in dbSNP:rs748676912)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071725"
FT VARIANT 975
FT /note="R -> W (in CCD; unknown pathological significance;
FT dbSNP:rs371278145)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071726"
FT VARIANT 1043
FT /note="R -> C (in MHS1; dbSNP:rs111272095)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058565"
FT VARIANT 1043
FT /note="R -> H (in MHS1; unknown pathological significance;
FT dbSNP:rs374776563)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071727"
FT VARIANT 1056
FT /note="D -> H (in MHS1)"
FT /evidence="ECO:0000269|PubMed:24013571"
FT /id="VAR_071728"
FT VARIANT 1056
FT /note="D -> N (in MHS1)"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071729"
FT VARIANT 1058
FT /note="E -> K (in MHS1)"
FT /evidence="ECO:0000269|PubMed:20142353"
FT /id="VAR_068511"
FT VARIANT 1088
FT /note="Y -> C (probable disease-associated variant found in
FT a family with Samaritan myopathy)"
FT /evidence="ECO:0000269|PubMed:22752422"
FT /id="VAR_068512"
FT VARIANT 1109
FT /note="R -> K (in dbSNP:rs35719391)"
FT /id="VAR_032912"
FT VARIANT 1109
FT /note="R -> L"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071730"
FT VARIANT 1127
FT /note="R -> H (in MHS1; dbSNP:rs545579559)"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071731"
FT VARIANT 1342
FT /note="S -> G (in dbSNP:rs34694816)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_032913"
FT VARIANT 1352
FT /note="A -> G (may be associated with susceptibility to
FT malignant hyperthermia; dbSNP:rs112105381)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058566"
FT VARIANT 1393
FT /note="K -> R (in MHS1; unknown pathological significance;
FT dbSNP:rs137933390)"
FT /evidence="ECO:0000269|PubMed:20142353,
FT ECO:0000269|PubMed:23558838"
FT /id="VAR_068513"
FT VARIANT 1467
FT /note="K -> R (in MHS1; dbSNP:rs145573319)"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071732"
FT VARIANT 1489
FT /note="S -> N (in dbSNP:rs34404839)"
FT /id="VAR_032914"
FT VARIANT 1571
FT /note="I -> V (in MHS1; dbSNP:rs146429605)"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071733"
FT VARIANT 1679
FT /note="R -> H (may be associated with susceptibility to
FT malignant hyperthermia; dbSNP:rs146504767)"
FT /evidence="ECO:0000269|PubMed:20142353"
FT /id="VAR_068514"
FT VARIANT 1704
FT /note="G -> S (in CCD; autosomal recessive form;
FT dbSNP:rs193922779)"
FT /evidence="ECO:0000269|PubMed:18253926"
FT /id="VAR_045709"
FT VARIANT 1787
FT /note="P -> L (may be associated with susceptibility to
FT malignant hyperthermia; dbSNP:rs34934920)"
FT /evidence="ECO:0000269|PubMed:1354642,
FT ECO:0000269|PubMed:19191329, ECO:0000269|PubMed:21674524,
FT ECO:0000269|PubMed:23558838"
FT /id="VAR_005599"
FT VARIANT 1832
FT /note="G -> A (in dbSNP:rs193922784)"
FT /evidence="ECO:0000269|PubMed:11928716,
FT ECO:0000269|PubMed:19191329, ECO:0000269|PubMed:8661021"
FT /id="VAR_045710"
FT VARIANT 2013
FT /note="K -> Q (in MHS1)"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071734"
FT VARIANT 2035
FT /note="H -> L (in MMDO; dbSNP:rs367543056)"
FT /evidence="ECO:0000269|PubMed:20583297"
FT /id="VAR_063847"
FT VARIANT 2060
FT /note="G -> C (may be associated with susceptibility to
FT malignant hyperthermia; dbSNP:rs35364374)"
FT /evidence="ECO:0000269|PubMed:1354642,
FT ECO:0000269|PubMed:16380615, ECO:0000269|PubMed:19191329,
FT ECO:0000269|PubMed:20681998, ECO:0000269|PubMed:21674524,
FT ECO:0000269|PubMed:23558838"
FT /id="VAR_005600"
FT VARIANT 2101
FT /note="M -> K (in dbSNP:rs746818096)"
FT /evidence="ECO:0000269|PubMed:12709367"
FT /id="VAR_045711"
FT VARIANT 2117
FT /note="V -> L (in MHS1; dbSNP:rs193922788)"
FT /evidence="ECO:0000269|PubMed:12709367"
FT /id="VAR_045712"
FT VARIANT 2129
FT /note="D -> E (in MHS1; dbSNP:rs117886618)"
FT /evidence="ECO:0000269|PubMed:11241852,
FT ECO:0000269|PubMed:12059893"
FT /id="VAR_045713"
FT VARIANT 2163
FT /note="R -> C (in MHS1; increases calcium-induced calcium
FT release activity; dbSNP:rs118192175)"
FT /evidence="ECO:0000269|PubMed:15448513,
FT ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:9497245,
FT ECO:0000305|PubMed:27586648"
FT /id="VAR_005601"
FT VARIANT 2163
FT /note="R -> H (in CCD and MHS1; increases calcium-induced
FT calcium release activity; dbSNP:rs118192163)"
FT /evidence="ECO:0000269|PubMed:12208234,
FT ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:23558838,
FT ECO:0000269|PubMed:9497245, ECO:0000305|PubMed:27586648"
FT /id="VAR_005602"
FT VARIANT 2163
FT /note="R -> P (in MHS1; dbSNP:rs118192163)"
FT /evidence="ECO:0000269|PubMed:12709367"
FT /id="VAR_008972"
FT VARIANT 2168
FT /note="V -> M (in CCD and MHS1; no difference in the
FT thapsigargin-sensitive calcium stores of cells carrying
FT this mutation and the wild-type; increases calcium-induced
FT calcium release activity; dbSNP:rs118192176)"
FT /evidence="ECO:0000269|PubMed:11575529,
FT ECO:0000269|PubMed:11709545, ECO:0000269|PubMed:11741831,
FT ECO:0000269|PubMed:12059893, ECO:0000269|PubMed:12709367,
FT ECO:0000269|PubMed:15448513, ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:23558838, ECO:0000269|PubMed:9497245,
FT ECO:0000305|PubMed:27586648"
FT /id="VAR_005603"
FT VARIANT 2204
FT /note="H -> Q (in CCD; dbSNP:rs141646642)"
FT /evidence="ECO:0000269|PubMed:21674524"
FT /id="VAR_068515"
FT VARIANT 2206
FT /note="T -> M (in MHS1; induces an increase sensitivity to
FT caffeine; dbSNP:rs118192177)"
FT /evidence="ECO:0000269|PubMed:11575529,
FT ECO:0000269|PubMed:12059893, ECO:0000269|PubMed:12208234,
FT ECO:0000269|PubMed:15448513, ECO:0000269|PubMed:23558838,
FT ECO:0000269|PubMed:9497245, ECO:0000305|PubMed:16163667,
FT ECO:0000305|PubMed:27586648"
FT /id="VAR_005604"
FT VARIANT 2206
FT /note="T -> R (in MHS1 and KDS; dbSNP:rs118192177)"
FT /evidence="ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:21514828"
FT /id="VAR_008973"
FT VARIANT 2214
FT /note="V -> I (in MHS1; dbSNP:rs193922795)"
FT /evidence="ECO:0000269|PubMed:11575529,
FT ECO:0000269|PubMed:15448513"
FT /id="VAR_045714"
FT VARIANT 2248
FT /note="R -> C (in dbSNP:rs763352221)"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071735"
FT VARIANT 2248
FT /note="R -> H (in MHS1; unknown pathological significance;
FT dbSNP:rs140152019)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071736"
FT VARIANT 2280
FT /note="V -> I (in MHS1; dbSNP:rs193922797)"
FT /evidence="ECO:0000269|PubMed:12208234"
FT /id="VAR_045715"
FT VARIANT 2321
FT /note="I -> V (in dbSNP:rs34390345)"
FT /evidence="ECO:0000269|PubMed:19191329,
FT ECO:0000269|PubMed:23558838"
FT /id="VAR_058567"
FT VARIANT 2336
FT /note="R -> H (in MHS1; dbSNP:rs112563513)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058568"
FT VARIANT 2342
FT /note="N -> S (in MHS1; dbSNP:rs147213895)"
FT /evidence="ECO:0000269|PubMed:15221887"
FT /id="VAR_045716"
FT VARIANT 2344
FT /note="E -> D (in MHS1; unknown pathological significance;
FT dbSNP:rs193922798)"
FT /evidence="ECO:0000269|PubMed:16163667"
FT /id="VAR_045717"
FT VARIANT 2346
FT /note="V -> M (in MHS1; dbSNP:rs193922799)"
FT /evidence="ECO:0000269|PubMed:14985404,
FT ECO:0000269|PubMed:16163667"
FT /id="VAR_045718"
FT VARIANT 2347
FT /note="Missing (in MHS1)"
FT /evidence="ECO:0000269|PubMed:11389482"
FT /id="VAR_045719"
FT VARIANT 2348
FT /note="E -> G (in MHS1; dbSNP:rs193922801)"
FT /evidence="ECO:0000269|PubMed:14985404"
FT /id="VAR_045720"
FT VARIANT 2350
FT /note="A -> T (in MHS1; reveals an altered calcium
FT dependence and increased caffeine sensitivity; increases
FT calcium-induced calcium release activity;
FT dbSNP:rs193922802)"
FT /evidence="ECO:0000269|PubMed:11525881,
FT ECO:0000269|PubMed:15448513, ECO:0000269|PubMed:16163667,
FT ECO:0000305|PubMed:27586648"
FT /id="VAR_045721"
FT VARIANT 2351
FT /note="N -> H (in MHS1; unknown pathological significance;
FT dbSNP:rs376176332)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071738"
FT VARIANT 2354
FT /note="V -> M (in MHS1; unknown pathological significance;
FT dbSNP:rs746971794)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071739"
FT VARIANT 2355
FT /note="R -> C (in MHS1)"
FT /evidence="ECO:0000269|PubMed:12123492"
FT /id="VAR_045722"
FT VARIANT 2358
FT /note="I -> L (in MHS1; unknown pathological significance;
FT dbSNP:rs759306349)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071740"
FT VARIANT 2367
FT /note="A -> T (in MHS1; dbSNP:rs146306934)"
FT /evidence="ECO:0000269|PubMed:11575529,
FT ECO:0000269|PubMed:15448513"
FT /id="VAR_045723"
FT VARIANT 2375
FT /note="G -> A (increases calcium-induced calcium release
FT activity; dbSNP:rs193922807)"
FT /evidence="ECO:0000305|PubMed:27586648"
FT /id="VAR_077682"
FT VARIANT 2383
FT /note="A -> Q (in MHS1; requires 2 nucleotide
FT substitutions; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071741"
FT VARIANT 2400
FT /note="D -> G (in MHS1; dbSNP:rs976108591)"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071742"
FT VARIANT 2404
FT /note="E -> K (in MHS1; dbSNP:rs111364296)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058569"
FT VARIANT 2421
FT /note="A -> P (in CCD; autosomal recessive form;
FT dbSNP:rs193922808)"
FT /evidence="ECO:0000269|PubMed:18253926"
FT /id="VAR_045724"
FT VARIANT 2423
FT /note="M -> K (in MMDO and CCD; autosomal recessive form;
FT dbSNP:rs118192174)"
FT /evidence="ECO:0000269|PubMed:16380615,
FT ECO:0000269|PubMed:18253926"
FT /id="VAR_032915"
FT VARIANT 2428
FT /note="A -> T (in MHS1; induces an increase sensitivity to
FT caffeine; dbSNP:rs193922809)"
FT /evidence="ECO:0000269|PubMed:12059893,
FT ECO:0000305|PubMed:16163667"
FT /id="VAR_045725"
FT VARIANT 2431
FT /note="D -> N (in MHS1; dbSNP:rs193922810)"
FT /evidence="ECO:0000269|PubMed:11575529,
FT ECO:0000269|PubMed:15448513"
FT /id="VAR_045726"
FT VARIANT 2434
FT /note="G -> R (in MHS1; increases calcium-induced calcium
FT release activity; dbSNP:rs121918593)"
FT /evidence="ECO:0000269|PubMed:11575529,
FT ECO:0000269|PubMed:12059893, ECO:0000269|PubMed:12208234,
FT ECO:0000269|PubMed:15448513, ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:23558838, ECO:0000269|PubMed:7849712,
FT ECO:0000269|PubMed:7881417, ECO:0000305|PubMed:27586648"
FT /id="VAR_005605"
FT VARIANT 2435
FT /note="R -> H (in CCD and MHS1; increases calcium-induced
FT calcium release activity; dbSNP:rs28933396)"
FT /evidence="ECO:0000269|PubMed:12059893,
FT ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:8220422,
FT ECO:0000305|PubMed:27586648"
FT /id="VAR_005606"
FT VARIANT 2435
FT /note="R -> L (in MHS1; dbSNP:rs28933396)"
FT /evidence="ECO:0000269|PubMed:10051009,
FT ECO:0000269|PubMed:12208234, ECO:0000269|PubMed:12709367"
FT /id="VAR_008974"
FT VARIANT 2437
FT /note="A -> V (in MHS1; dbSNP:rs193922812)"
FT /evidence="ECO:0000269|PubMed:15448513"
FT /id="VAR_045727"
FT VARIANT 2452
FT /note="R -> W (in MHS1 and KDS; dbSNP:rs118192124)"
FT /evidence="ECO:0000269|PubMed:10823104,
FT ECO:0000269|PubMed:12059893, ECO:0000269|PubMed:14985404,
FT ECO:0000269|PubMed:21514828"
FT /id="VAR_045728"
FT VARIANT 2454
FT /note="R -> C (in MHS1; induces an increase sensitivity to
FT caffeine; increases calcium-induced calcium release
FT activity; dbSNP:rs193922816)"
FT /evidence="ECO:0000269|PubMed:10612851,
FT ECO:0000269|PubMed:12411788, ECO:0000305|PubMed:16163667,
FT ECO:0000305|PubMed:27586648"
FT /id="VAR_008975"
FT VARIANT 2454
FT /note="R -> H (in MHS1; severe form; increases calcium-
FT induced calcium release activity; dbSNP:rs118192122)"
FT /evidence="ECO:0000269|PubMed:10051009,
FT ECO:0000269|PubMed:10823104, ECO:0000269|PubMed:11575529,
FT ECO:0000269|PubMed:12059893, ECO:0000269|PubMed:12709367,
FT ECO:0000269|PubMed:15448513, ECO:0000269|PubMed:23558838,
FT ECO:0000305|PubMed:16163667, ECO:0000305|PubMed:27586648"
FT /id="VAR_008976"
FT VARIANT 2458
FT /note="R -> C (in MHS1; dbSNP:rs28933397)"
FT /evidence="ECO:0000269|PubMed:12208234,
FT ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:9450902,
FT ECO:0000305|PubMed:27586648"
FT /id="VAR_008977"
FT VARIANT 2458
FT /note="R -> H (in MHS1; dbSNP:rs121918594)"
FT /evidence="ECO:0000269|PubMed:14985404,
FT ECO:0000269|PubMed:9450902, ECO:0000305|PubMed:27586648"
FT /id="VAR_008978"
FT VARIANT 2508
FT /note="R -> C (in MHS1, CCD and KDS; increases sensitivity
FT to caffeine and 4-chloro-m-cresol; increases calcium-
FT induced calcium release activity; dbSNP:rs118192178)"
FT /evidence="ECO:0000269|PubMed:19685112,
FT ECO:0000269|PubMed:27918309, ECO:0000305|PubMed:27586648"
FT /id="VAR_075399"
FT VARIANT 2508
FT /note="R -> G (in CCD; increases sensitivity to caffeine
FT and 4-chloro-m-cresol; dbSNP:rs118192178)"
FT /evidence="ECO:0000269|PubMed:20142353,
FT ECO:0000269|PubMed:26381711"
FT /id="VAR_068516"
FT VARIANT 2508
FT /note="R -> H (in MHS1; increases sensitivity to caffeine
FT and 4-chloro-m-cresol; increases calcium-induced calcium
FT release activity; dbSNP:rs193922818)"
FT /evidence="ECO:0000269|PubMed:26381711,
FT ECO:0000305|PubMed:27586648"
FT /id="VAR_077683"
FT VARIANT 2509
FT /note="V -> I (in dbSNP:rs2071088)"
FT /id="VAR_051891"
FT VARIANT 2550
FT /note="L -> V (in dbSNP:rs193922821)"
FT /evidence="ECO:0000269|PubMed:1354642,
FT ECO:0000269|PubMed:19191329, ECO:0000269|PubMed:8661021"
FT /id="VAR_058570"
FT VARIANT 2593
FT /note="R -> G (in MHS1; dbSNP:rs756685891)"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071743"
FT VARIANT 2627
FT /note="V -> M (in MHS1)"
FT /evidence="ECO:0000269|PubMed:24013571"
FT /id="VAR_071744"
FT VARIANT 2676
FT /note="R -> W (associated in cis with S-2787; may be
FT associated with susceptibility to malignant hyperthermia;
FT dbSNP:rs193922826)"
FT /evidence="ECO:0000269|PubMed:14732627,
FT ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:19191329"
FT /id="VAR_045729"
FT VARIANT 2730
FT /note="D -> G (in MHS1; dbSNP:rs112196644)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058571"
FT VARIANT 2776
FT /note="S -> F (in KDS; unknown pathological significance;
FT dbSNP:rs147707463)"
FT /evidence="ECO:0000269|PubMed:21514828"
FT /id="VAR_086257"
FT VARIANT 2779
FT /note="E -> K (in dbSNP:rs2915952)"
FT /id="VAR_051892"
FT VARIANT 2787
FT /note="T -> S (associated in cis with W-2676; may be
FT associated with susceptibility to malignant hyperthermia;
FT dbSNP:rs35180584)"
FT /evidence="ECO:0000269|PubMed:14732627,
FT ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:19191329"
FT /id="VAR_045730"
FT VARIANT 2880
FT /note="E -> K (in MHS1; dbSNP:rs112772310)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058572"
FT VARIANT 2963
FT /note="L -> P (in CCD; dbSNP:rs756870293)"
FT /evidence="ECO:0000269|PubMed:27234031"
FT /id="VAR_076568"
FT VARIANT 2976
FT /note="H -> Y"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071745"
FT VARIANT 3118
FT /note="A -> V (in dbSNP:rs2915960)"
FT /id="VAR_045731"
FT VARIANT 3217
FT /note="S -> P (in MHS1; dbSNP:rs113422327)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058573"
FT VARIANT 3238
FT /note="E -> G (in CCD; unknown pathological significance;
FT dbSNP:rs200950673)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071746"
FT VARIANT 3290
FT /note="E -> K (in MHS1; dbSNP:rs112151058)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058574"
FT VARIANT 3326
FT /note="N -> K (in MMDO; dbSNP:rs367543057)"
FT /evidence="ECO:0000269|PubMed:20583297"
FT /id="VAR_063848"
FT VARIANT 3360
FT /note="P -> Q"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071747"
FT VARIANT 3366
FT /note="R -> H (in CCD; dbSNP:rs137932199)"
FT /evidence="ECO:0000269|PubMed:21674524"
FT /id="VAR_068517"
FT VARIANT 3402
FT /note="C -> G (in MMDO; dbSNP:rs367543058)"
FT /evidence="ECO:0000269|PubMed:20583297"
FT /id="VAR_063849"
FT VARIANT 3410
FT /note="P -> Q (in MHS1)"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071748"
FT VARIANT 3501
FT /note="D -> Y (in MHS1; dbSNP:rs763259167)"
FT /evidence="ECO:0000269|PubMed:20681998"
FT /id="VAR_071749"
FT VARIANT 3527
FT /note="P -> S (in CCD; autosomal recessive form;
FT dbSNP:rs118192164)"
FT /evidence="ECO:0000269|PubMed:12112081"
FT /id="VAR_045732"
FT VARIANT 3539
FT /note="R -> H (in CCD; autosomal recessive form;
FT dbSNP:rs143987857)"
FT /evidence="ECO:0000269|PubMed:18253926"
FT /id="VAR_045733"
FT VARIANT 3583
FT /note="E -> Q (in dbSNP:rs55876273)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058575"
FT VARIANT 3711
FT /note="T -> R (in MHS1; unknown pathological significance;
FT dbSNP:rs375915752)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071750"
FT VARIANT 3756
FT /note="Q -> E (in dbSNP:rs4802584)"
FT /evidence="ECO:0000269|PubMed:11928716,
FT ECO:0000269|PubMed:19191329"
FT /id="VAR_032916"
FT VARIANT 3772
FT /note="R -> Q (in CCD; autosomal recessive form;
FT dbSNP:rs193922839)"
FT /evidence="ECO:0000269|PubMed:18253926"
FT /id="VAR_045734"
FT VARIANT 3772
FT /note="R -> W (in MHS1; dbSNP:rs763112609)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058576"
FT VARIANT 3806
FT /note="G -> R (in MHS1; dbSNP:rs111565359)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058577"
FT VARIANT 3916
FT /note="I -> M (in MHS1; dbSNP:rs193922840)"
FT /evidence="ECO:0000269|PubMed:12411788,
FT ECO:0000269|PubMed:16163667"
FT /id="VAR_045735"
FT VARIANT 3933
FT /note="Y -> C (in CCD and MHS1; dbSNP:rs147136339)"
FT /evidence="ECO:0000269|PubMed:20681998,
FT ECO:0000269|PubMed:21674524"
FT /id="VAR_068518"
FT VARIANT 4136
FT /note="R -> S (in MHS1; dbSNP:rs193922849)"
FT /evidence="ECO:0000269|PubMed:12208234"
FT /id="VAR_045736"
FT VARIANT 4178
FT /note="G -> V (in MHS1; unknown pathological significance;
FT dbSNP:rs1568576165)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071751"
FT VARIANT 4214..4216
FT /note="Missing (in CCD)"
FT /id="VAR_045737"
FT VARIANT 4230
FT /note="M -> R (in MHS1; unknown pathological significance;
FT dbSNP:rs1568581848)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071752"
FT VARIANT 4234
FT /note="V -> L (in MHS1; dbSNP:rs193922852)"
FT /evidence="ECO:0000269|PubMed:12208234,
FT ECO:0000269|PubMed:24013571"
FT /id="VAR_045738"
FT VARIANT 4493
FT /note="P -> A (in dbSNP:rs149455643)"
FT /evidence="ECO:0000269|PubMed:21674524"
FT /id="VAR_068519"
FT VARIANT 4501
FT /note="P -> L (may be associated with susceptibility to
FT malignant hyperthermia; dbSNP:rs73933023)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058578"
FT VARIANT 4558
FT /note="R -> Q (in CCD; autosomal recessive form;
FT dbSNP:rs118192130)"
FT /evidence="ECO:0000269|PubMed:17226826,
FT ECO:0000269|PubMed:18253926"
FT /id="VAR_045739"
FT VARIANT 4637
FT /note="T -> A (in CCD; dbSNP:rs118192166)"
FT /evidence="ECO:0000269|PubMed:11113224"
FT /id="VAR_045740"
FT VARIANT 4637
FT /note="T -> I (in core/rod disease; dbSNP:rs118192134)"
FT /evidence="ECO:0000269|PubMed:12565913"
FT /id="VAR_045741"
FT VARIANT 4638
FT /note="G -> D (in CCD; dbSNP:rs118192135)"
FT /evidence="ECO:0000269|PubMed:12565913,
FT ECO:0000269|PubMed:14985404"
FT /id="VAR_045742"
FT VARIANT 4647..4648
FT /note="Missing (in CCD)"
FT /evidence="ECO:0000269|PubMed:11709545"
FT /id="VAR_045743"
FT VARIANT 4650
FT /note="L -> P (in CCD; autosomal recessive form;
FT dbSNP:rs118192138)"
FT /evidence="ECO:0000269|PubMed:12937085"
FT /id="VAR_045744"
FT VARIANT 4651
FT /note="H -> P (in CCD; dbSNP:rs118192139)"
FT /evidence="ECO:0000269|PubMed:12565913"
FT /id="VAR_045745"
FT VARIANT 4668
FT /note="P -> S (in dbSNP:rs193922863)"
FT /evidence="ECO:0000269|PubMed:11928716"
FT /id="VAR_045746"
FT VARIANT 4684
FT /note="F -> S (in MHS1; dbSNP:rs193922864)"
FT /evidence="ECO:0000269|PubMed:16163667"
FT /id="VAR_045747"
FT VARIANT 4724
FT /note="K -> Q (in CCD; autosomal recessive form;
FT dbSNP:rs118192141)"
FT /evidence="ECO:0000269|PubMed:12937085"
FT /id="VAR_045748"
FT VARIANT 4737
FT /note="R -> Q (in MHS1; dbSNP:rs193922868)"
FT /evidence="ECO:0000269|PubMed:16163667"
FT /id="VAR_045749"
FT VARIANT 4737
FT /note="R -> W (in MHS1; unknown pathological significance;
FT slightly increases Ca(2+) release in response to 4-chloro-
FT m-cresol; dbSNP:rs193922867)"
FT /evidence="ECO:0000269|PubMed:12208234,
FT ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:26631338"
FT /id="VAR_045750"
FT VARIANT 4743
FT /note="G -> D (in CCD; dbSNP:rs193922869)"
FT /evidence="ECO:0000269|PubMed:21674524"
FT /id="VAR_068520"
FT VARIANT 4793
FT /note="L -> P (in CCD; dbSNP:rs118192179)"
FT /evidence="ECO:0000269|PubMed:11709545"
FT /id="VAR_045751"
FT VARIANT 4796
FT /note="Y -> C (in CCD; dbSNP:rs118192167)"
FT /evidence="ECO:0000269|PubMed:11709545"
FT /id="VAR_045752"
FT VARIANT 4806
FT /note="N -> D (in CCD; dbSNP:rs886039586)"
FT /evidence="ECO:0000269|PubMed:27234031"
FT /id="VAR_076569"
FT VARIANT 4814
FT /note="L -> F (in CCD; dbSNP:rs118192142)"
FT /evidence="ECO:0000269|PubMed:14985404"
FT /id="VAR_045753"
FT VARIANT 4824
FT /note="L -> P (in MHS1; dbSNP:rs193922874)"
FT /evidence="ECO:0000269|PubMed:14985404,
FT ECO:0000269|PubMed:15448513"
FT /id="VAR_045754"
FT VARIANT 4825
FT /note="R -> C (in CCD; dbSNP:rs118192180)"
FT /evidence="ECO:0000269|PubMed:11709545"
FT /id="VAR_045755"
FT VARIANT 4826
FT /note="T -> I (in MHS1; dbSNP:rs121918595)"
FT /evidence="ECO:0000269|PubMed:10888602,
FT ECO:0000269|PubMed:16163667"
FT /id="VAR_045756"
FT VARIANT 4837
FT /note="Q -> E (in MHS1; unknown pathological significance;
FT dbSNP:rs1568604577)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071753"
FT VARIANT 4838
FT /note="L -> V (in MHS1; dbSNP:rs193922878)"
FT /evidence="ECO:0000269|PubMed:11928716,
FT ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:19191329"
FT /id="VAR_045757"
FT VARIANT 4842
FT /note="V -> M (in CCD; autosomal recessive form;
FT dbSNP:rs193922879)"
FT /evidence="ECO:0000269|PubMed:18253926"
FT /id="VAR_045758"
FT VARIANT 4846
FT /note="A -> V (in CCD; autosomal recessive form;
FT dbSNP:rs118192143)"
FT /evidence="ECO:0000269|PubMed:17204054,
FT ECO:0000269|PubMed:17226826"
FT /id="VAR_045759"
FT VARIANT 4849
FT /note="V -> I (in MHS1 and CCD; autosomal recessive form;
FT dbSNP:rs118192168)"
FT /evidence="ECO:0000269|PubMed:12136074,
FT ECO:0000269|PubMed:16163667, ECO:0000269|PubMed:17226826,
FT ECO:0000269|PubMed:18253926"
FT /id="VAR_045760"
FT VARIANT 4860
FT /note="Missing (in CCD; dbSNP:rs118192145)"
FT /evidence="ECO:0000269|PubMed:11709545"
FT /id="VAR_045761"
FT VARIANT 4861
FT /note="R -> C (in CCD; dbSNP:rs118192181)"
FT /evidence="ECO:0000269|PubMed:12565913,
FT ECO:0000269|PubMed:17226826"
FT /id="VAR_045762"
FT VARIANT 4861
FT /note="R -> H (in CCD and MHS1; release of calcium from
FT intracellular stores in the absence of any pharmacological
FT activator of RYR; dbSNP:rs63749869)"
FT /evidence="ECO:0000269|PubMed:11709545,
FT ECO:0000269|PubMed:11741831, ECO:0000269|PubMed:12565913,
FT ECO:0000269|PubMed:14670767, ECO:0000269|PubMed:14985404,
FT ECO:0000269|PubMed:17226826, ECO:0000269|PubMed:23558838,
FT ECO:0000269|PubMed:24561095"
FT /id="VAR_045763"
FT VARIANT 4863..4869
FT /note="FYNKSED -> Y (in CCD)"
FT /id="VAR_045764"
FT VARIANT 4864
FT /note="Y -> C (in CCD; dbSNP:rs118192146)"
FT /evidence="ECO:0000269|PubMed:14670767"
FT /id="VAR_045765"
FT VARIANT 4876
FT /note="K -> R (in MHS1; dbSNP:rs113210953)"
FT /evidence="ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:19191329"
FT /id="VAR_045766"
FT VARIANT 4882
FT /note="T -> M (in CCD; dbSNP:rs193922884)"
FT /evidence="ECO:0000269|PubMed:18312400"
FT /id="VAR_068521"
FT VARIANT 4891
FT /note="G -> R (in CCD; dbSNP:rs118192149)"
FT /evidence="ECO:0000269|PubMed:11741831"
FT /id="VAR_045767"
FT VARIANT 4893
FT /note="R -> Q (in CCD; dbSNP:rs118192151)"
FT /evidence="ECO:0000269|PubMed:12565913"
FT /id="VAR_045768"
FT VARIANT 4893
FT /note="R -> W (in CCD; release of calcium from
FT intracellular stores in the absence of any pharmacological
FT activator of RYR; smaller thapsigargin-sensitive
FT intracellular calcium stores; normal sensitivity of the
FT calcium release to the RYR inhibitor dantrolene;
FT dbSNP:rs118192150)"
FT /evidence="ECO:0000269|PubMed:11709545,
FT ECO:0000269|PubMed:11741831, ECO:0000269|PubMed:14670767"
FT /id="VAR_045769"
FT VARIANT 4897
FT /note="G -> A (in CCD)"
FT /evidence="ECO:0000269|PubMed:24561095"
FT /id="VAR_071754"
FT VARIANT 4897
FT /note="G -> V (in CCD; dbSNP:rs118192148)"
FT /evidence="ECO:0000269|PubMed:17226826"
FT /id="VAR_045770"
FT VARIANT 4898
FT /note="I -> T (in CCD; severe phenotype;
FT dbSNP:rs118192170)"
FT /evidence="ECO:0000269|PubMed:10097181,
FT ECO:0000269|PubMed:11709545, ECO:0000269|PubMed:11741831,
FT ECO:0000269|PubMed:12565913, ECO:0000269|PubMed:24561095"
FT /id="VAR_045771"
FT VARIANT 4899
FT /note="G -> E (in CCD; dbSNP:rs118192183)"
FT /evidence="ECO:0000269|PubMed:11709545,
FT ECO:0000269|PubMed:12937085"
FT /id="VAR_045772"
FT VARIANT 4899
FT /note="G -> R (in CCD; release of calcium from
FT intracellular stores in the absence of any pharmacological
FT activator of RYR; smaller thapsigargin-sensitive
FT intracellular calcium stores; normal sensitivity of the
FT calcium release to the RYR inhibitor dantrolene;
FT dbSNP:rs193922891)"
FT /evidence="ECO:0000269|PubMed:11741831"
FT /id="VAR_045773"
FT VARIANT 4906
FT /note="A -> G (in MHS1; unknown pathological significance;
FT dbSNP:rs118192153)"
FT /evidence="ECO:0000269|PubMed:23558838"
FT /id="VAR_071755"
FT VARIANT 4906
FT /note="A -> V (in CCD; dbSNP:rs118192153)"
FT /evidence="ECO:0000269|PubMed:11741831"
FT /id="VAR_045774"
FT VARIANT 4914
FT /note="R -> G (in CCD; dbSNP:rs118192184)"
FT /evidence="ECO:0000269|PubMed:11709545,
FT ECO:0000269|PubMed:12565913"
FT /id="VAR_045775"
FT VARIANT 4914
FT /note="R -> T (in CCD; dbSNP:rs118192154)"
FT /evidence="ECO:0000269|PubMed:12565913,
FT ECO:0000269|PubMed:17226826"
FT /id="VAR_045776"
FT VARIANT 4927..4928
FT /note="Missing (in CCD)"
FT /evidence="ECO:0000269|PubMed:12565913"
FT /id="VAR_045777"
FT VARIANT 4938
FT /note="I -> M (in CCD; dbSNP:rs118192159)"
FT /evidence="ECO:0000269|PubMed:14985404"
FT /id="VAR_045778"
FT VARIANT 4938
FT /note="I -> T (in MHS1; dbSNP:rs111657878)"
FT /evidence="ECO:0000269|PubMed:19191329"
FT /id="VAR_058579"
FT VARIANT 4939
FT /note="D -> E (in MHS1; dbSNP:rs193922895)"
FT /evidence="ECO:0000269|PubMed:14985404,
FT ECO:0000269|PubMed:16163667"
FT /id="VAR_045779"
FT VARIANT 4940
FT /note="A -> T (in CCD; dbSNP:rs118192158)"
FT /evidence="ECO:0000269|PubMed:12565913,
FT ECO:0000269|PubMed:14670767"
FT /id="VAR_045780"
FT VARIANT 4942
FT /note="G -> V (in MHS1; dbSNP:rs193922896)"
FT /evidence="ECO:0000269|PubMed:12208234"
FT /id="VAR_045781"
FT VARIANT 4973
FT /note="P -> L (in MHS1; dbSNP:rs146876145)"
FT /evidence="ECO:0000269|PubMed:12208234,
FT ECO:0000269|PubMed:12411788, ECO:0000269|PubMed:16163667"
FT /id="VAR_045782"
FT MUTAGEN 522
FT /note="Y->C: Increases calcium-induced calcium release
FT activity."
FT /evidence="ECO:0000269|PubMed:26115329"
FT MUTAGEN 2508
FT /note="R->K: Increases sensitivity to caffeine and 4-
FT chloro-m-cresol."
FT /evidence="ECO:0000269|PubMed:26381711"
FT MUTAGEN 2508
FT /note="R->S: Increases sensitivity to caffeine and 4-
FT chloro-m-cresol."
FT /evidence="ECO:0000269|PubMed:26381711"
FT CONFLICT 1365..1368
FT /note="GEAQ -> RGA (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 2324
FT /note="N -> K (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 2840
FT /note="R -> A (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 3380
FT /note="R -> A (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 864..887
FT /evidence="ECO:0007829|PDB:6UHS"
FT TURN 898..901
FT /evidence="ECO:0007829|PDB:6UHS"
FT HELIX 909..911
FT /evidence="ECO:0007829|PDB:6UHS"
FT HELIX 914..933
FT /evidence="ECO:0007829|PDB:6UHS"
FT STRAND 936..940
FT /evidence="ECO:0007829|PDB:6UHS"
SQ SEQUENCE 5038 AA; 565176 MW; EC32277F4885CC7F CRC64;
MGDAEGEDEV QFLRTDDEVV LQCSATVLKE QLKLCLAAEG FGNRLCFLEP TSNAQNVPPD
LAICCFVLEQ SLSVRALQEM LANTVEAGVE SSQGGGHRTL LYGHAILLRH AHSRMYLSCL
TTSRSMTDKL AFDVGLQEDA TGEACWWTMH PASKQRSEGE KVRVGDDIIL VSVSSERYLH
LSTASGELQV DASFMQTLWN MNPICSRCEE GFVTGGHVLR LFHGHMDECL TISPADSDDQ
RRLVYYEGGA VCTHARSLWR LEPLRISWSG SHLRWGQPLR VRHVTTGQYL ALTEDQGLVV
VDASKAHTKA TSFCFRISKE KLDVAPKRDV EGMGPPEIKY GESLCFVQHV ASGLWLTYAA
PDPKALRLGV LKKKAMLHQE GHMDDALSLT RCQQEESQAA RMIHSTNGLY NQFIKSLDSF
SGKPRGSGPP AGTALPIEGV ILSLQDLIIY FEPPSEDLQH EEKQSKLRSL RNRQSLFQEE
GMLSMVLNCI DRLNVYTTAA HFAEFAGEEA AESWKEIVNL LYELLASLIR GNRSNCALFS
TNLDWLVSKL DRLEASSGIL EVLYCVLIES PEVLNIIQEN HIKSIISLLD KHGRNHKVLD
VLCSLCVCNG VAVRSNQDLI TENLLPGREL LLQTNLINYV TSIRPNIFVG RAEGTTQYSK
WYFEVMVDEV TPFLTAQATH LRVGWALTEG YTPYPGAGEG WGGNGVGDDL YSYGFDGLHL
WTGHVARPVT SPGQHLLAPE DVISCCLDLS VPSISFRING CPVQGVFESF NLDGLFFPVV
SFSAGVKVRF LLGGRHGEFK FLPPPGYAPC HEAVLPRERL HLEPIKEYRR EGPRGPHLVG
PSRCLSHTDF VPCPVDTVQI VLPPHLERIR EKLAENIHEL WALTRIEQGW TYGPVRDDNK
RLHPCLVDFH SLPEPERNYN LQMSGETLKT LLALGCHVGM ADEKAEDNLK KTKLPKTYMM
SNGYKPAPLD LSHVRLTPAQ TTLVDRLAEN GHNVWARDRV GQGWSYSAVQ DIPARRNPRL
VPYRLLDEAT KRSNRDSLCQ AVRTLLGYGY NIEPPDQEPS QVENQSRCDR VRIFRAEKSY
TVQSGRWYFE FEAVTTGEMR VGWARPELRP DVELGADELA YVFNGHRGQR WHLGSEPFGR
PWQPGDVVGC MIDLTENTII FTLNGEVLMS DSGSETAFRE IEIGDGFLPV CSLGPGQVGH
LNLGQDVSSL RFFAICGLQE GFEPFAINMQ RPVTTWFSKG LPQFEPVPLE HPHYEVSRVD
GTVDTPPCLR LTHRTWGSQN SLVEMLFLRL SLPVQFHQHF RCTAGATPLA PPGLQPPAED
EARAAEPDPD YENLRRSAGG WSEAENGKEG TAKEGAPGGT PQAGGEAQPA RAENEKDATT
EKNKKRGFLF KAKKVAMMTQ PPATPTLPRL PHDVVPADNR DDPEIILNTT TYYYSVRVFA
GQEPSCVWAG WVTPDYHQHD MSFDLSKVRV VTVTMGDEQG NVHSSLKCSN CYMVWGGDFV
SPGQQGRISH TDLVIGCLVD LATGLMTFTA NGKESNTFFQ VEPNTKLFPA VFVLPTHQNV
IQFELGKQKN IMPLSAAMFQ SERKNPAPQC PPRLEMQMLM PVSWSRMPNH FLQVETRRAG
ERLGWAVQCQ EPLTMMALHI PEENRCMDIL ELSERLDLQR FHSHTLRLYR AVCALGNNRV
AHALCSHVDQ AQLLHALEDA HLPGPLRAGY YDLLISIHLE SACRSRRSML SEYIVPLTPE
TRAITLFPPG RSTENGHPRH GLPGVGVTTS LRPPHHFSPP CFVAALPAAG AAEAPARLSP
AIPLEALRDK ALRMLGEAVR DGGQHARDPV GGSVEFQFVP VLKLVSTLLV MGIFGDEDVK
QILKMIEPEV FTEEEEEEDE EEEGEEEDEE EKEEDEEETA QEKEDEEKEE EEAAEGEKEE
GLEEGLLQMK LPESVKLQMC HLLEYFCDQE LQHRVESLAA FAERYVDKLQ ANQRSRYGLL
IKAFSMTAAE TARRTREFRS PPQEQINMLL QFKDGTDEED CPLPEEIRQD LLDFHQDLLA
HCGIQLDGEE EEPEEETTLG SRLMSLLEKV RLVKKKEEKP EEERSAEESK PRSLQELVSH
MVVRWAQEDF VQSPELVRAM FSLLHRQYDG LGELLRALPR AYTISPSSVE DTMSLLECLG
QIRSLLIVQM GPQEENLMIQ SIGNIMNNKV FYQHPNLMRA LGMHETVMEV MVNVLGGGES
KEIRFPKMVT SCCRFLCYFC RISRQNQRSM FDHLSYLLEN SGIGLGMQGS TPLDVAAASV
IDNNELALAL QEQDLEKVVS YLAGCGLQSC PMLVAKGYPD IGWNPCGGER YLDFLRFAVF
VNGESVEENA NVVVRLLIRK PECFGPALRG EGGSGLLAAI EEAIRISEDP ARDGPGIRRD
RRREHFGEEP PEENRVHLGH AIMSFYAALI DLLGRCAPEM HLIQAGKGEA LRIRAILRSL
VPLEDLVGII SLPLQIPTLG KDGALVQPKM SASFVPDHKA SMVLFLDRVY GIENQDFLLH
VLDVGFLPDM RAAASLDTAT FSTTEMALAL NRYLCLAVLP LITKCAPLFA GTEHRAIMVD
SMLHTVYRLS RGRSLTKAQR DVIEDCLMSL CRYIRPSMLQ HLLRRLVFDV PILNEFAKMP
LKLLTNHYER CWKYYCLPTG WANFGVTSEE ELHLTRKLFW GIFDSLAHKK YDPELYRMAM
PCLCAIAGAL PPDYVDASYS SKAEKKATVD AEGNFDPRPV ETLNVIIPEK LDSFINKFAE
YTHEKWAFDK IQNNWSYGEN IDEELKTHPM LRPYKTFSEK DKEIYRWPIK ESLKAMIAWE
WTIEKAREGE EEKTEKKKTR KISQSAQTYD PREGYNPQPP DLSAVTLSRE LQAMAEQLAE
NYHNTWGRKK KQELEAKGGG THPLLVPYDT LTAKEKARDR EKAQELLKFL QMNGYAVTRG
LKDMELDSSS IEKRFAFGFL QQLLRWMDIS QEFIAHLEAV VSSGRVEKSP HEQEIKFFAK
ILLPLINQYF TNHCLYFLST PAKVLGSGGH ASNKEKEMIT SLFCKLAALV RHRVSLFGTD
APAVVNCLHI LARSLDARTV MKSGPEIVKA GLRSFFESAS EDIEKMVENL RLGKVSQART
QVKGVGQNLT YTTVALLPVL TTLFQHIAQH QFGDDVILDD VQVSCYRTLC SIYSLGTTKN
TYVEKLRPAL GECLARLAAA MPVAFLEPQL NEYNACSVYT TKSPRERAIL GLPNSVEEMC
PDIPVLERLM ADIGGLAESG ARYTEMPHVI EITLPMLCSY LPRWWERGPE APPSALPAGA
PPPCTAVTSD HLNSLLGNIL RIIVNNLGID EASWMKRLAV FAQPIVSRAR PELLQSHFIP
TIGRLRKRAG KVVSEEEQLR LEAKAEAQEG ELLVRDEFSV LCRDLYALYP LLIRYVDNNR
AQWLTEPNPS AEELFRMVGE IFIYWSKSHN FKREEQNFVV QNEINNMSFL TADNKSKMAK
AGDIQSGGSD QERTKKKRRG DRYSVQTSLI VATLKKMLPI GLNMCAPTDQ DLITLAKTRY
ALKDTDEEVR EFLHNNLHLQ GKVEGSPSLR WQMALYRGVP GREEDADDPE KIVRRVQEVS
AVLYYLDQTE HPYKSKKAVW HKLLSKQRRR AVVACFRMTP LYNLPTHRAC NMFLESYKAA
WILTEDHSFE DRMIDDLSKA GEQEEEEEEV EEKKPDPLHQ LVLHFSRTAL TEKSKLDEDY
LYMAYADIMA KSCHLEEGGE NGEAEEEVEV SFEEKQMEKQ RLLYQQARLH TRGAAEMVLQ
MISACKGETG AMVSSTLKLG ISILNGGNAE VQQKMLDYLK DKKEVGFFQS IQALMQTCSV
LDLNAFERQN KAEGLGMVNE DGTVINRQNG EKVMADDEFT QDLFRFLQLL CEGHNNDFQN
YLRTQTGNTT TINIIICTVD YLLRLQESIS DFYWYYSGKD VIEEQGKRNF SKAMSVAKQV
FNSLTEYIQG PCTGNQQSLA HSRLWDAVVG FLHVFAHMMM KLAQDSSQIE LLKELLDLQK
DMVVMLLSLL EGNVVNGMIA RQMVDMLVES SSNVEMILKF FDMFLKLKDI VGSEAFQDYV
TDPRGLISKK DFQKAMDSQK QFSGPEIQFL LSCSEADENE MINCEEFANR FQEPARDIGF
NVAVLLTNLS EHVPHDPRLH NFLELAESIL EYFRPYLGRI EIMGASRRIE RIYFEISETN
RAQWEMPQVK ESKRQFIFDV VNEGGEAEKM ELFVSFCEDT IFEMQIAAQI SEPEGEPETD
EDEGAGAAEA GAEGAEEGAA GLEGTAATAA AGATARVVAA AGRALRGLSY RSLRRRVRRL
RRLTAREAAT AVAALLWAAV TRAGAAGAGA AAGALGLLWG SLFGGGLVEG AKKVTVTELL
AGMPDPTSDE VHGEQPAGPG GDADGEGASE GAGDAAEGAG DEEEAVHEAG PGGADGAVAV
TDGGPFRPEG AGGLGDMGDT TPAEPPTPEG SPILKRKLGV DGVEEELPPE PEPEPEPELE
PEKADAENGE KEEVPEPTPE PPKKQAPPSP PPKKEEAGGE FWGELEVQRV KFLNYLSRNF
YTLRFLALFL AFAINFILLF YKVSDSPPGE DDMEGSAAGD VSGAGSGGSS GWGLGAGEEA
EGDEDENMVY YFLEESTGYM EPALRCLSLL HTLVAFLCII GYNCLKVPLV IFKREKELAR
KLEFDGLYIT EQPEDDDVKG QWDRLVLNTP SFPSNYWDKF VKRKVLDKHG DIYGRERIAE
LLGMDLATLE ITAHNERKPN PPPGLLTWLM SIDVKYQIWK FGVIFTDNSF LYLGWYMVMS
LLGHYNNFFF AAHLLDIAMG VKTLRTILSS VTHNGKQLVM TVGLLAVVVY LYTVVAFNFF
RKFYNKSEDE DEPDMKCDDM MTCYLFHMYV GVRAGGGIGD EIEDPAGDEY ELYRVVFDIT
FFFFVIVILL AIIQGLIIDA FGELRDQQEQ VKEDMETKCF ICGIGSDYFD TTPHGFETHT
LEEHNLANYM FFLMYLINKD ETEHTGQESY VWKMYQERCW DFFPAGDCFR KQYEDQLS
