Human Gene RYR2 (ENST00000366574.7) from GENCODE V44
  Description: Homo sapiens ryanodine receptor 2 (RYR2), mRNA. (from RefSeq NM_001035)
RefSeq Summary (NM_001035): This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia. [provided by RefSeq, Jul 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments.
Gencode Transcript: ENST00000366574.7
Gencode Gene: ENSG00000198626.18
Transcript (Including UTRs)
   Position: hg38 chr1:237,042,184-237,833,988 Size: 791,805 Total Exon Count: 105 Strand: +
Coding Region
   Position: hg38 chr1:237,042,522-237,832,647 Size: 790,126 Coding Exon Count: 105 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:237,042,184-237,833,988)mRNA (may differ from genome)Protein (4967 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGImyGene2
neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: RYR2_HUMAN
DESCRIPTION: RecName: Full=Ryanodine receptor 2; Short=RYR-2; Short=RyR2; Short=hRYR-2; AltName: Full=Cardiac muscle ryanodine receptor; AltName: Full=Cardiac muscle ryanodine receptor-calcium release channel; AltName: Full=Type 2 ryanodine receptor;
FUNCTION: Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development.
SUBUNIT: Homotetramer. Can also form heterotetramers with RYR1 and RYR3 (By similarity). Interacts with FKBP1A and FKBP1B; these interactions may stabilize the channel in its closed state and prevent Ca(2+) leaks. Interacts with CALM and S100A1; these interactions regulate channel activity. Identified in a complex composed of RYR2, FKBP1B, PKA catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A and PP1. Interacts directly with FKBP1B, PKA, PP1 and PP2A.
INTERACTION: Q00987:MDM2; NbExp=2; IntAct=EBI-1170425, EBI-389668;
SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane; Multi-pass membrane protein. Membrane; Multi-pass membrane protein (Probable). Note=The number of predicted transmembrane domains varies between orthologs, but both N-terminus and C-terminus seem to be cytoplasmic (By similarity).
TISSUE SPECIFICITY: Detected in heart muscle (at protein level). Heart muscle, brain (cerebellum and hippocampus) and placenta.
DEVELOPMENTAL STAGE: Expressed in myometrium during pregnancy.
INDUCTION: By TGFB1.
DOMAIN: The calcium release channel activity resides in the C- terminal region while the remaining part of the protein resides in the cytoplasm (Probable).
PTM: Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2808 and Ser-2814 increases the open probability of the calcium channel. Phosphorylation is increased in failing heart, leading to calcium leaks and increased cytoplasmic Ca(2+) levels.
DISEASE: Defects in RYR2 are the cause of familial arrhythmogenic right ventricular dysplasia type 2 (ARVD2) [MIM:600996]; also known as arrhythmogenic right ventricular cardiomyopathy 2 (ARVC2). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall.
DISEASE: Defects in RYR2 are the cause of catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) [MIM:604772]; also known as stress-induced polymorphic ventricular tachycardia (VTSIP). CPVT1 is an autosomal dominant form of arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death.
MISCELLANEOUS: Channel activity is modulated by the alkaloid ryanodine that binds to the open Ca-release channel with high affinity. At low concentrations, ryanodine maintains the channel in an open conformation. High ryanodine concentrations inhibit channel activity. Channel activity is regulated by calmodulin (CALM). The calcium release is activated by increased cytoplasmic calcium levels, by nitric oxyde (NO), caffeine and ATP. Channel activity is inhibited by magnesium ions, possibly by competition for calcium binding sites (By similarity).
SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2 subfamily.
SIMILARITY: Contains 3 B30.2/SPRY domains.
SIMILARITY: Contains 5 MIR domains.
SEQUENCE CAUTION: Sequence=CAH71369.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAH71393.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAH73918.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAI14440.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAI15350.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAI15936.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAI22065.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RYR2";
WEB RESOURCE: Name=Wikipedia; Note=Ryanodine receptor entry; URL="http://en.wikipedia.org/wiki/Ryanodine_receptor";
WEB RESOURCE: Name=Wikipedia; Note=RYR2 entry; URL="http://en.wikipedia.org/wiki/RYR2";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: RYR2
Diseases sorted by gene-association score: ventricular tachycardia, catecholaminergic polymorphic, 1* (1241), arrhythmogenic right ventricular dysplasia 2* (1227), catecholaminergic polymorphic ventricular tachycardia* (568), familial isolated arrhythmogenic ventricular dysplasia, right dominant form* (350), familial isolated arrhythmogenic ventricular dysplasia, biventricular form* (350), familial isolated arrhythmogenic ventricular dysplasia, left dominant form* (350), ventricular fibrillation, familial, 1* (294), arrhythmogenic right ventricular dysplasia/cardiomyopathy 2* (100), ryr2-related catecholaminergic polymorphic ventricular tachycardia* (100), heart disease (20), arrhythmogenic right ventricular cardiomyopathy (16), central core disease (13), dilated cardiomyopathy (12), malignant hyperthermia (11), cardiac arrest (9), cardiomyopathy (9), heart conduction disease (8), arrhythmogenic right ventricular dysplasia 8 (8), long qt syndrome (8), cyclic vomiting syndrome (7), arrhythmogenic right ventricular dysplasia 9 (7), arrhythmogenic right ventricular dysplasia 1 (7), long qt syndrome 6 (6), left ventricular noncompaction (6), long qt syndrome 2 (5), muscle disorders (5), long qt syndrome 5 (5), sudden infant death syndrome (4), atrial fibrillation (4), long qt syndrome 1 (3), intrinsic cardiomyopathy (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 68.22 RPKM in Heart - Left Ventricle
Total median expression: 208.22 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -204.80338-0.606 Picture PostScript Text
3' UTR -307.701341-0.229 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001870 - B30.2/SPRY
IPR000699 - Ca-rel_channel
IPR008985 - ConA-like_lec_gl_sf
IPR011992 - EF-hand-like_dom
IPR018249 - EF_HAND_2
IPR002048 - EF_hand_Ca-bd
IPR014821 - Ins145_P3_rcpt
IPR005821 - Ion_trans_dom
IPR016093 - MIR_motif
IPR013662 - RIH_assoc-dom
IPR013333 - Ryan_recept
IPR003032 - Ryanodine_rcpt
IPR015925 - Ryanodine_recept-rel
IPR009460 - Ryanrecept_TM4-6
IPR018355 - SPla/RYanodine_receptor_subgr
IPR003877 - SPRY_rcpt

Pfam Domains:
PF08709 - Inositol 1,4,5-trisphosphate/ryanodine receptor
PF00520 - Ion transport protein
PF02815 - MIR domain
PF08454 - RyR and IP3R Homology associated
PF06459 - Ryanodine Receptor TM 4-6
PF01365 - RIH domain
PF02026 - RyR domain
PF00622 - SPRY domain

ModBase Predicted Comparative 3D Structure on Q92736
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
MGIRGD  WormBase 
Protein SequenceProtein Sequence  Protein Sequence 
AlignmentAlignment  Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005216 ion channel activity
GO:0005219 ryanodine-sensitive calcium-release channel activity
GO:0005262 calcium channel activity
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0005516 calmodulin binding
GO:0015278 calcium-release channel activity
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0034236 protein kinase A catalytic subunit binding
GO:0034237 protein kinase A regulatory subunit binding
GO:0042802 identical protein binding
GO:0043621 protein self-association
GO:0043924 suramin binding
GO:0044325 ion channel binding
GO:0048763 calcium-induced calcium release activity
GO:0097159 organic cyclic compound binding

Biological Process:
GO:0001666 response to hypoxia
GO:0002027 regulation of heart rate
GO:0003143 embryonic heart tube morphogenesis
GO:0003220 left ventricular cardiac muscle tissue morphogenesis
GO:0003300 cardiac muscle hypertrophy
GO:0005513 detection of calcium ion
GO:0006811 ion transport
GO:0006816 calcium ion transport
GO:0006874 cellular calcium ion homeostasis
GO:0007275 multicellular organism development
GO:0010460 positive regulation of heart rate
GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
GO:0010882 regulation of cardiac muscle contraction by calcium ion signaling
GO:0014808 release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
GO:0014850 response to muscle activity
GO:0019722 calcium-mediated signaling
GO:0030509 BMP signaling pathway
GO:0031000 response to caffeine
GO:0034220 ion transmembrane transport
GO:0035584 calcium-mediated signaling using intracellular calcium source
GO:0035994 response to muscle stretch
GO:0051209 release of sequestered calcium ion into cytosol
GO:0051284 positive regulation of sequestering of calcium ion
GO:0051480 regulation of cytosolic calcium ion concentration
GO:0051775 response to redox state
GO:0055085 transmembrane transport
GO:0055117 regulation of cardiac muscle contraction
GO:0060048 cardiac muscle contraction
GO:0060070 canonical Wnt signaling pathway
GO:0060401 cytosolic calcium ion transport
GO:0060402 calcium ion transport into cytosol
GO:0070296 sarcoplasmic reticulum calcium ion transport
GO:0070588 calcium ion transmembrane transport
GO:0071313 cellular response to caffeine
GO:0071872 cellular response to epinephrine stimulus
GO:0072599 establishment of protein localization to endoplasmic reticulum
GO:0086005 ventricular cardiac muscle cell action potential
GO:0086029 Purkinje myocyte to ventricular cardiac muscle cell signaling
GO:0086064 cell communication by electrical coupling involved in cardiac conduction
GO:0097050 type B pancreatic cell apoptotic process
GO:0098735 positive regulation of the force of heart contraction
GO:0098904 regulation of AV node cell action potential
GO:0098907 regulation of SA node cell action potential
GO:0098910 regulation of atrial cardiac muscle cell action potential
GO:0098911 regulation of ventricular cardiac muscle cell action potential
GO:1901896 positive regulation of calcium-transporting ATPase activity
GO:1903779 regulation of cardiac conduction

Cellular Component:
GO:0005790 smooth endoplasmic reticulum
GO:0005886 plasma membrane
GO:0014701 junctional sarcoplasmic reticulum membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016529 sarcoplasmic reticulum
GO:0030017 sarcomere
GO:0030018 Z disc
GO:0032991 macromolecular complex
GO:0033017 sarcoplasmic reticulum membrane
GO:0034704 calcium channel complex


-  Descriptions from all associated GenBank mRNAs
  X98330 - H.sapiens mRNA for ryanodine receptor 2.
BC172794 - Synthetic construct Homo sapiens clone IMAGE:9094280 cardiac muscle ryanodine receptor (RYR2) gene, partial cds.
Y08218 - H.sapiens mRNA for ryanodine receptor 2.
AK294792 - Homo sapiens cDNA FLJ54506 partial cds, highly similar to Ryanodine receptor 2.
BC172780 - Synthetic construct Homo sapiens clone IMAGE:9094266 cardiac muscle ryanodine receptor (RYR2) gene, partial cds.
JD462503 - Sequence 443527 from Patent EP1572962.
JD191102 - Sequence 172126 from Patent EP1572962.
AB204532 - Homo sapiens RyR mRNA for cardiac-type ryaodine receptor, partial cds.
AB204534 - Homo sapiens RyR mRNA for islet-type ryanodine receptor, partial cds.
AB204535 - Homo sapiens RyR mRNA for kidney-type ryanodine receptor, partial cds.
LP857455 - Sequence 2 from Patent WO2017141157.
LP857456 - Sequence 3 from Patent WO2017141157.
LP857472 - Sequence 19 from Patent WO2017141157.
LP857473 - Sequence 20 from Patent WO2017141157.
LP857488 - Sequence 35 from Patent WO2017141157.
LP857487 - Sequence 34 from Patent WO2017141157.
LP857486 - Sequence 33 from Patent WO2017141157.
LP857485 - Sequence 32 from Patent WO2017141157.
LP857484 - Sequence 31 from Patent WO2017141157.
LP857483 - Sequence 30 from Patent WO2017141157.
LP857482 - Sequence 29 from Patent WO2017141157.
LP857481 - Sequence 28 from Patent WO2017141157.
LP857480 - Sequence 27 from Patent WO2017141157.
LP857479 - Sequence 26 from Patent WO2017141157.
LP857478 - Sequence 25 from Patent WO2017141157.
LP857477 - Sequence 24 from Patent WO2017141157.
LP857476 - Sequence 23 from Patent WO2017141157.
LP857475 - Sequence 22 from Patent WO2017141157.
LP857474 - Sequence 21 from Patent WO2017141157.
X91869 - H.sapiens mRNA for ryanodine receptor.
BC172779 - Synthetic construct Homo sapiens clone IMAGE:9094265 cardiac muscle ryanodine receptor (RYR2) gene, partial cds.
LP857489 - Sequence 36 from Patent WO2017141157.
LP857490 - Sequence 37 from Patent WO2017141157.
LP857506 - Sequence 53 from Patent WO2017141157.
LP857507 - Sequence 54 from Patent WO2017141157.
LP857522 - Sequence 69 from Patent WO2017141157.
LP857521 - Sequence 68 from Patent WO2017141157.
LP857520 - Sequence 67 from Patent WO2017141157.
LP857519 - Sequence 66 from Patent WO2017141157.
LP857518 - Sequence 65 from Patent WO2017141157.
LP857517 - Sequence 64 from Patent WO2017141157.
LP857516 - Sequence 63 from Patent WO2017141157.
LP857515 - Sequence 62 from Patent WO2017141157.
LP857514 - Sequence 61 from Patent WO2017141157.
LP857513 - Sequence 60 from Patent WO2017141157.
LP857512 - Sequence 59 from Patent WO2017141157.
LP857511 - Sequence 58 from Patent WO2017141157.
LP857510 - Sequence 57 from Patent WO2017141157.
LP857509 - Sequence 56 from Patent WO2017141157.
LP857508 - Sequence 55 from Patent WO2017141157.
LP857523 - Sequence 70 from Patent WO2017141157.
LP857524 - Sequence 71 from Patent WO2017141157.
LP857540 - Sequence 87 from Patent WO2017141157.
LP857541 - Sequence 88 from Patent WO2017141157.
LP857557 - Sequence 104 from Patent WO2017141157.
LP857556 - Sequence 103 from Patent WO2017141157.
LP857555 - Sequence 102 from Patent WO2017141157.
LP857554 - Sequence 101 from Patent WO2017141157.
LP857553 - Sequence 100 from Patent WO2017141157.
LP857552 - Sequence 99 from Patent WO2017141157.
LP857551 - Sequence 98 from Patent WO2017141157.
LP857550 - Sequence 97 from Patent WO2017141157.
LP857549 - Sequence 96 from Patent WO2017141157.
LP857548 - Sequence 95 from Patent WO2017141157.
LP857547 - Sequence 94 from Patent WO2017141157.
LP857546 - Sequence 93 from Patent WO2017141157.
LP857545 - Sequence 92 from Patent WO2017141157.
LP857544 - Sequence 91 from Patent WO2017141157.
LP857543 - Sequence 90 from Patent WO2017141157.
LP857542 - Sequence 89 from Patent WO2017141157.
AK294729 - Homo sapiens cDNA FLJ58358 complete cds, highly similar to Ryanodine receptor 2.
AB204533 - Homo sapiens RyR mRNA for cardiac-type ryanodine receptor, partial cds.
AB204536 - Homo sapiens RyR mRNA for islet-type ryanodine receptor, partial cds.
AJ002511 - Homo sapiens mRNA for ryanodine receptor 2, partial.
AK297823 - Homo sapiens cDNA FLJ61140 complete cds, highly similar to Ryanodine receptor 2.
JD379160 - Sequence 360184 from Patent EP1572962.
JD301772 - Sequence 282796 from Patent EP1572962.
JD036912 - Sequence 17936 from Patent EP1572962.
JD202704 - Sequence 183728 from Patent EP1572962.
JD437835 - Sequence 418859 from Patent EP1572962.
JD144299 - Sequence 125323 from Patent EP1572962.
JD303637 - Sequence 284661 from Patent EP1572962.
JD037200 - Sequence 18224 from Patent EP1572962.
JD261484 - Sequence 242508 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04020 - Calcium signaling pathway
hsa04260 - Cardiac muscle contraction
hsa05410 - Hypertrophic cardiomyopathy (HCM)
hsa05412 - Arrhythmogenic right ventricular cardiomyopathy (ARVC)
hsa05414 - Dilated cardiomyopathy

BioCarta from NCI Cancer Genome Anatomy Project
h_no1Pathway - Actions of Nitric Oxide in the Heart

Reactome (by CSHL, EBI, and GO)

Protein Q92736 (Reactome details) participates in the following event(s):

R-HSA-2855020 RYR tetramers transport Ca2+ from sarcoplasmic reticulum lumen to cytosol
R-HSA-2672351 Stimuli-sensing channels
R-HSA-5578775 Ion homeostasis
R-HSA-983712 Ion channel transport
R-HSA-5576891 Cardiac conduction
R-HSA-382551 Transport of small molecules
R-HSA-397014 Muscle contraction

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000366574.1, ENST00000366574.2, ENST00000366574.3, ENST00000366574.4, ENST00000366574.5, ENST00000366574.6, NM_001035, Q15411, Q546N8, Q5T3P2, Q92736, RYR2_HUMAN, uc001hyl.1, uc001hyl.2, uc001hyl.3
UCSC ID: ENST00000366574.7
RefSeq Accession: NM_001035
Protein: Q92736 (aka RYR2_HUMAN)
CCDS: CCDS55691.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene RYR2:
hyper-card (Hypertrophic Cardiomyopathy Overview)
cvt (Catecholaminergic Polymorphic Ventricular Tachycardia)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.