RYR2 Gene (Ryanodine Receptor 2)
Key regulator of cardiac calcium-induced calcium release and associated with arrhythmogenic disorders
Gene Information Card
| Symbol | RYR2 |
|---|---|
| Full Name | Ryanodine Receptor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q43 |
| NCBI Gene ID | 6262 ncbi.nlm.nih.gov/gene/6262 |
| Ensembl ID | ENSG00000198626 |
| UniProt ID | Q92736 |
| OMIM ID | 180902 |
| HGNC ID | 10484 |
| Aliases | ARVC2, ARVD2, VTSIP, hRYR-2, RyR2, RYR-2 |
Description
The RYR2 gene encodes the ryanodine receptor 2, a large intracellular calcium release channel expressed predominantly in cardiac muscle. It mediates calcium release from the sarcoplasmic reticulum following calcium influx through L-type calcium channels, a process essential for excitation-contraction coupling in the heart. Mutations in RYR2 are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) and arrhythmogenic right ventricular cardiomyopathy (ARVC).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) | Gain-of-function mutations increase diastolic calcium leak from the sarcoplasmic reticulum, triggering delayed afterdepolarizations and arrhythmias under stress | ClinVar, OMIM |
| Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) | Loss-of-function or dominant-negative mutations impair channel stability and calcium handling, leading to myocyte death and fibrofatty replacement | ClinVar, OMIM |
| Sudden Cardiac Death | Pathogenic RYR2 variants predispose to lethal arrhythmias, especially in young individuals without structural heart disease | ClinVar, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 78.5 | High |
| Skeletal Muscle | 12.3 | Medium |
| Brain | 5.1 | Low |
| Liver | 0.2 | Not detected |
| Kidney | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPS-derived) | 85.2 | High expression; used in functional studies |
| HEK293 | 0.5 | Low endogenous; often used for recombinant expression |
| SH-SY5Y | 2.1 | Low; neuronal expression reported |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1259G>A (p.Arg420Gln) | Missense | Rare | Gain-of-function; increased channel open probability |
| c.4499T>C (p.Leu1500Pro) | Missense | Rare | Loss-of-function; reduced calcium release |
| c.1231C>T (p.Arg411Cys) | Missense | Rare | Dominant-negative; impaired channel assembly |
Mutation functional classification
Loss of Function (LOF)
Reduced calcium release or channel expression; associated with ARVC phenotypes.
Gain of Function (GOF)
Increased diastolic calcium leak; strongly linked to CPVT and stress-induced arrhythmias.
Dominant Negative (DN)
Mutant subunits disrupt wild-type channel function; observed in some ARVC families.
View complete mutation data：
Gene Ontology (GO)
| • Calcium ion transmembrane transport | • Calcium-induced calcium release |
| • Ryanodine-sensitive calcium-release channel activity | • Sarcoplasmic reticulum calcium ion transport |
| • Cardiac muscle contraction | • Regulation of heart contraction |
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Cardiac muscle contraction (KEGG: hsa04260)
• Adrenergic signaling in cardiomyocytes (KEGG: hsa04261)
Protein Summary
The ryanodine receptor 2 (RyR2) is a homotetrameric calcium channel of approximately 2.2 MDa, localized to the sarcoplasmic reticulum membrane in cardiac myocytes. It is the primary mediator of calcium-induced calcium release, coupling membrane depolarization to muscle contraction. RyR2 is regulated by cytosolic calcium, ATP, and phosphorylation. Pathogenic variants alter channel gating, leading to arrhythmogenic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RYR2 Knockout HEK293 Cell Line | EDJ-KQ1426 | Human | 6262 | Details Get a Quote |
| RYR2 Knockout HeLa Cell Line | EDJ-KQ54375 | Human | 6262 | Details Get a Quote |
| RYR2 Knockout A-549 Cell Line | EDJ-KQ62869 | Human | 6262 | Details Get a Quote |
| RYR2 Knockout HCT 116 Cell Line | EDJ-KQ71334 | Human | 6262 | Details Get a Quote |
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