RYR2
Chr 1ADryanodine receptor 2
Also known as: ARVC2, ARVD2, RYR-2, RyR, VACRDS, VTSIP
This gene encodes a cardiac ryanodine receptor that functions as a cytosolic calcium-activated calcium channel, mediating calcium release from the sarcoplasmic reticulum to trigger cardiac muscle contraction. Mutations cause catecholaminergic polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is likely not tolerated.
Limited evidence — not for standalone diagnostic reporting
4 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Extremely missense-constrained (top ~0.01%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
RYR2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Tissue and Metabolic Characterization of Arrhythmogenic Cardiomyopathies by Hybrid PET-MRI Imaging, Impact of the Observed Profiles on the Phenotype and on the Evolution of Cardiomyopathy
RECRUITINGA Study of SGT-501 Gene Therapy in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
RECRUITINGInternational CRDS Registry
RECRUITINGExternal Resources
Links to major genomics databases and tools