
Gene Report
Approved Symbol | RYR2 |
---|---|
Approved Name | ryanodine receptor 2 (cardiac) |
Previous Symbol | ARVD2 |
Previous Name | "arrhythmogenic right ventricular dysplasia 2" |
Symbol Alias | ARVC2, VTSIP |
Location | 1q43 |
Position | chr1:237995948-237997288 (+) |
External Links |
Entrez Gene: 6262 Ensembl: ENSG00000198626 UCSC: uc001hyl.1 HGNC ID: 10484 |
No. of Studies (Positive/Negative) | 1(1/0)
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Type | Literature-origin |
Name in Literature | Reference | Research Type | Statistical Result | Relation Description | ![]() |
---|---|---|---|---|---|
RYR2 | Guilloux JP, 2012 | patients and normal controls | genes significantly affected in female MDD subjects genes significantly affected in female MDD subjects |
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1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus | Protein and Other Molecule | Cell and Molecular Pathway | Neural System | Cognition and Behavior | Symptoms and Signs | Environment | MDD |
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2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Gene mapped GO terms | ||||
ID | Name | Type | Evidence | |
---|---|---|---|---|
GO:0034704 | calcium channel complex | cellular component | IDA[10830164|16213210] | |
GO:0005509 | calcium ion binding | molecular function | IEA | |
GO:0010881 | regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion | biological process | IC[19220289]; ISS | |
GO:0048763 | calcium-induced calcium release activity | molecular function | IDA[17921453] | |
GO:0071313 | cellular response to caffeine | biological process | IDA[12919952]; ISS | |
GO:0019722 | calcium-mediated signaling | biological process | ISS | |
GO:0030018 | Z disc | cellular component | ISS | |
GO:0070296 | sarcoplasmic reticulum calcium ion transport | biological process | TAS[19095005] | |
GO:0098735 | positive regulation of the force of heart contraction | biological process | IMP[15105296] | |
GO:0035584 | calcium-mediated signaling using intracellular calcium source | biological process | IDA[17921453] | |
GO:0005790 | smooth endoplasmic reticulum | cellular component | IEA | |
GO:0033017 | sarcoplasmic reticulum membrane | cellular component | ISS; TAS[19095005] | |
GO:0055085 | transmembrane transport | biological process | TAS | |
GO:0042802 | identical protein binding | molecular function | IPI[10830164] | |
GO:0003300 | cardiac muscle hypertrophy | biological process | ISS | |
GO:0043234 | protein complex | cellular component | IDA[18468998] | |
GO:0043621 | protein self-association | molecular function | IEA | |
GO:0015278 | calcium-release channel activity | molecular function | IDA[17921453] | |
GO:0006874 | cellular calcium ion homeostasis | biological process | ISS | |
GO:0001666 | response to hypoxia | biological process | ISS | |
GO:0031000 | response to caffeine | biological process | IDA[17921453] | |
GO:0005515 | protein binding | molecular function | IPI[10830164|11237759|17921453|20195357|23233753] | |
GO:0014701 | junctional sarcoplasmic reticulum membrane | cellular component | TAS[17569730] | |
GO:0060402 | calcium ion transport into cytosol | biological process | IDA[17921453] | |
GO:0051284 | positive regulation of sequestering of calcium ion | biological process | IDA[12443530|12919952] | |
GO:0030509 | BMP signaling pathway | biological process | IEA | |
GO:0051775 | response to redox state | biological process | IDA[19226252] | |
GO:0086064 | cell communication by electrical coupling involved in cardiac conduction | biological process | IC | |
GO:0034237 | protein kinase A regulatory subunit binding | molecular function | IDA[10830164] | |
GO:0060048 | cardiac muscle contraction | biological process | IMP[10830164] | |
GO:0044325 | ion channel binding | molecular function | ISS | |
GO:0014850 | response to muscle activity | biological process | IMP[17875969] | |
GO:0002027 | regulation of heart rate | biological process | IMP[11159936|12919952|15197150] | |
GO:0098907 | regulation of SA node cell action potential | biological process | IMP[17875969] | |
GO:0016529 | sarcoplasmic reticulum | cellular component | IDA[10830164|12919952] | |
GO:0005886 | plasma membrane | cellular component | ISS | |
GO:0003220 | left ventricular cardiac muscle tissue morphogenesis | biological process | ISS | |
GO:1903779 | regulation of cardiac conduction | biological process | TAS | |
GO:0055117 | regulation of cardiac muscle contraction | biological process | IMP[11159936] | |
GO:0003143 | embryonic heart tube morphogenesis | biological process | ISS | |
GO:0061337 | cardiac conduction | biological process | TAS | |
GO:0086029 | Purkinje myocyte to ventricular cardiac muscle cell signaling | biological process | ISS | |
GO:0034220 | ion transmembrane transport | biological process | TAS | |
GO:0071872 | cellular response to epinephrine stimulus | biological process | ISS; TAS[23507255] | |
GO:0006816 | calcium ion transport | biological process | IDA[17921453] | |
GO:0014808 | release of sequestered calcium ion into cytosol by sarcoplasmic reticulum | biological process | IMP[12919952]; ISS | |
GO:1901896 | positive regulation of calcium-transporting ATPase activity | biological process | IDA[12443530] | |
GO:0010882 | regulation of cardiac muscle contraction by calcium ion signaling | biological process | IMP[17875969] | |
GO:0072599 | establishment of protein localization to endoplasmic reticulum | biological process | IDA[12443530] | |
GO:0086005 | ventricular cardiac muscle cell action potential | biological process | ISS | |
GO:0005516 | calmodulin binding | molecular function | IMP[19220289]; IPI[23040497]; ISS | |
GO:0043924 | suramin binding | molecular function | IMP[19220289] | |
GO:0051209 | release of sequestered calcium ion into cytosol | biological process | IDA[12443530|17921453]; ISS | |
GO:0005262 | calcium channel activity | molecular function | ISS | |
GO:0034236 | protein kinase A catalytic subunit binding | molecular function | IDA[10830164] | |
GO:0070062 | extracellular exosome | cellular component | IDA[23376485] | |
GO:0010460 | positive regulation of heart rate | biological process | ISS | |
GO:0098910 | regulation of atrial cardiac muscle cell action potential | biological process | IMP[17875969] | |
GO:0097050 | type B pancreatic cell apoptotic process | biological process | IMP[15044459] | |
GO:0005219 | ryanodine-sensitive calcium-release channel activity | molecular function | IDA[17921453] | |
GO:0098911 | regulation of ventricular cardiac muscle cell action potential | biological process | IMP[17875969] | |
GO:0019899 | enzyme binding | molecular function | IPI[16213210] | |
GO:0051480 | regulation of cytosolic calcium ion concentration | biological process | ISS | |
GO:0016020 | membrane | cellular component | IDA[12443530] | |
GO:0005829 | cytosol | cellular component | ISS | |
GO:0060070 | canonical Wnt signaling pathway | biological process | IEA | |
GO:0035994 | response to muscle stretch | biological process | IMP[15105296] | |
GO:0098904 | regulation of AV node cell action potential | biological process | IMP[17875969] | |
GO:0005513 | detection of calcium ion | biological process | IDA[10830164] |
Literature-origin KEGG pathway | ||||
ID | Name | Brief Description | Full Description | |
---|---|---|---|---|
hsa05412 | arrhythmogenic right_ventricular_cardiomyopathy_arvc | Arrhythmogenic right ventricular cardiomyopathy (ARVC) | Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an...... Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are progressive myocyte loss and fibrofatty replacement, with a predilection for the right ventricle. A number of genetic studies have identified mutations in various components of the cardiac desmosome that have important roles in the pathogenesis of ARVD/C. Disruption of desmosomal function by defective proteins might lead to death of myocytes under mechanical stress. The myocardial injury may be accompanied by inflammation. Since regeneration of cardiac myocytes is limited, repair by fibrofatty replacement occurs. Several studies have implicated that desmosome dysfunction results in the delocalization and nuclear translocation of plakoglobin. As a result, competition between plakoglobin and beta-catenin will lead to the inhibition of Wnt/beta-catenin signaling, resulting in a shift from a myocyte fate towards an adipocyte fate of cells. The ryanodine receptor plays a crucial part in electromechanical coupling by control of release of calcium from the sarcoplasmic reticulum into the cytosol. Therefore, defects in this receptor could result in an imbalance of calcium homeostasis that might trigger cell death. More... | |
hsa04020 | calcium signaling_pathway | Calcium signaling pathway | Ca2+ that enters the cell from the outside is a principal so...... Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it. The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM). More... |
Gene mapped KEGG pathways | ||||
ID | Name | Brief Description | Full Description | |
---|---|---|---|---|
hsa05410 | hypertrophic cardiomyopathy_hcm | Hypertrophic cardiomyopathy (HCM) | Hypertrophic cardiomyopathy (HCM) is a primary myocardial di...... Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological features of myocyte hypertrophy, myofibrillar disarray, and interstitial fibrosis. HCM is one of the most common inherited cardiac disorders, with a prevalence in young adults of 1 in 500. Hundreds of mutations in 11 genes that encode protein constituents of the sarcomere have been identified in HCM. These mutations increase the Ca2+ sensitivity of cardiac myofilaments. Increased myofilament Ca2+ sensitivity is expected to increase the ATP utilization by actomyosin at submaximal Ca2+ concentrations, which might cause an imbalance in energy supply and demand in the heart under severe stress. The inefficient use of ATP suggests that an inability to maintain normal ATP levels could be the central abnormality. This theory might be supported by the discovery of the role of a mutant PRKAG2 gene in HCM, which in active form acts as a central sensing mechanism protecting cells from depletion of ATP supplies. The increase in the myofilament Ca2+ sensitivity well account for the diastolic dysfunction of model animals as well as human patients of HCM. It has been widely proposed that left ventricular hypertrophy is not a primary manifestation but develops as compensatory response to sarcomere dysfunction. More... | |
hsa04260 | cardiac muscle_contraction | Cardiac muscle contraction | Contraction of the heart is a complex process initiated by t...... Contraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation of voltage-dependent L-type Ca channels (DHP receptors) upon membrane depolarization triggers the release of Ca2+ via Ca2+ release channels (ryanodine receptors) of sarcoplasmic reticulum (SR) through a Ca2+ -induced Ca release (CICR) mechanism. Ca2+ ions released via the CICR mechanism diffuse through the cytosolic space to contractile proteins to bind to troponinC resulting in the release of inhibition induced by troponinI. The Ca2+ binding to troponinC thereby triggers the sliding of thin and thick filaments, that is, the activation of a crossbridge and subsequent cardiac force development and/or cell shortening. Recovery occurs as Ca2+ is pumped out of the cell by the Na+/Ca2+ exchanger (NCX) or is returned to the sarcoplasmic reticulum (SR) by sarco(endo)plasmic Ca2+ -ATPase (SERCA) pumps on the non-junctional region of the SR. More... | |
hsa05414 | dilated cardiomyopathy | Dilated cardiomyopathy | Dilated cardiomyopathy (DCM) is a heart muscle disease chara...... Dilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac death from ventricular arrhythmia. Genetically inherited forms of DCM (familial DCM) have been identified in 25-35% of patients presenting with this disease, and the inherited gene defects are an important cause of familial DCM. The pathophysiology may be separated into two categories: defects in force generation and defects in force transmission. In cases where an underlying pathology cannot be identified, the patient is diagnosed with an idiopathic DCM. Current hypotheses regarding causes of idiopathic DCM focus on chronic viral myocarditis and/or on autoimmune abnormalities. Viral myocarditis may progress to an autoimmune phase and then to progressive cardiac dilatation. Antibodies to the beta1-adrenergic receptor (beta1AR), which are detected in a substantial number of patients with idiopathic DCM, may increase the concentration of intracellular cAMP and intracellular Ca2+, a condition often leading to a transient hyper-performance of the heart followed by depressed heart function and heart failure. More... |
Gene mapped BioCarta pathways | ||||
ID | Name | Brief Description | Full Description | |
---|---|---|---|---|
NO1_PATHWAY | no1 pathway | Actions of Nitric Oxide in the Heart | Nitric oxide (NO) has a number of important physiological ac...... Nitric oxide (NO) has a number of important physiological actions in the cardiovascular system. In the heart, NO plays role in keeping the vessels patent via vasodilation and prevention of platelet aggregation. It also plays an important role in regulating the force and rate of contraction. In vivo NO is released by shear stress of ligands that increase intracellular Ca2+ in endothelial cells. The increase intracellular Ca2+ activates nitric oxide synthase III (NOSIII) by promoting the binding of Ca/Calmodulin to the enzyme. NOSIII, which is resident in the Golgi complex, is transported together with caveolin-1 to the caveolae at the plasma membrane via vesicles. Shear stress signals via a potassium channel and the cytoskeleton, which results in tyrosine phosphorylation of specific proteins, activation of phosphatidylinositol 3-kinase, and subsequently in activation of Akt kinase. Akt activation by shear stress but also by VEGF activates NOSIII by serine phosphorylation, which increases the affinity of NOSIII for calmodulin. After agonist binding at the plasma membrane, NOSIII-activating receptors translocate to caveolae. VEGF receptor signals via its tyrosine kinase domain. Furthermore, agonist receptors activate calcium channels of the endoplasmic reticulum (ER) via phospholipase C and inositol 1,4,5-trisphosphate. This calcium flux induces binding of calmodulin to NOSIII, whereas the NOSIII-caveolin-1 interaction is disrupted. At the same time, NOSIII is translocated into the cytosol. On binding of calmodulin, NOSIII generates NO, is enhanced by the interaction with Hsp90. Once activated, NOSIII catabolizes L-arginine to NO, which diffuses out of the cell. NO stimulates guanylate (G-) cyclase and increases cGMP levels. cGMP activates cGMP-dependent protein kinase (PKG), cGMP-inhibited phosphodiesterase (PDEIII), and cGMP-stimulated phosphodiesterase (PDEII). PKG may reduce the force and rate of contraction, possibly by phosphorylating troponin I or by phosphorylating phospholamban. PDEIII is inhibited by the increases in cGMP brought about by NO. This may result in an increase in cAMP and cAMP-dependent protein kinase (PKA). PKA in turn activates Ca2+ channels, countering the effects of PKG. In contrast, cGMP may stimulate PDEII, reduce cAMP levels and PKA activity, and thereby reduce Ca2+ channel activity. Ach, acetylcholine. CAT-1, cationic amino acid transporter. More... |

Gene | Interactor | Interactor in MK4MDD? | Experiment Type | PMID | |
---|---|---|---|---|---|
RYR2 | SRI | No | in vivo | 7592856 | |
RYR2 | ALB | No | in vivo | 15174051 | |
RYR2 | PRKACA | No | in vitro;in vivo | 10830164 | |
RYR2 | SMAD5 | No | yeast 2-hybrid | 15231748 | |
RYR2 | CACNA1C | Yes | in vitro | 11576544 | |
RYR2 | ITPR1 | Yes | in vivo | 12754204 | |
RYR2 | HOMER1 | No | in vitro;in vivo | 12887973 | |
RYR2 | FKBP1B | No | in vitro;in vivo;yeast 2-hybrid | 12446682 , 12443530 , 10830164 , 11237759 | |
RYR2 | PRKAR2A | Yes | in vitro;in vivo | 10830164 | |
RYR2 | AKAP6 | No | in vivo | 11352932 | |
RYR2 | RYR1 | No | in vivo | 12213830 | |
RYR2 | RYR3 | No | in vivo | 12213830 |