Gene RYR2

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Also known as

Ryanodine Receptor 2, ARVC2, ARVD2, CPVT1, VTSIP

Overview

RYR2 (Ryanodine Receptor 2) encodes the cardiac ryanodine receptor, a massive calcium channel protein located in the sarcoplasmic reticulum of heart muscle cells. This receptor plays a critical role in excitation-contraction coupling, the process by which electrical signals trigger heart muscle contraction. When activated by a small influx of calcium through voltage-gated channels, RYR2 releases large amounts of stored calcium from the sarcoplasmic reticulum into the cytoplasm, enabling the synchronized contraction of cardiac myocytes that produces each heartbeat.

Mutations in RYR2 are primarily associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), a life-threatening inherited arrhythmia syndrome characterized by exercise- or stress-induced ventricular arrhythmias that can lead to syncope and sudden cardiac death, typically in children and young adults with structurally normal hearts. RYR2 mutations can also cause arrhythmogenic right ventricular cardiomyopathy (ARVC). These mutations typically result in abnormal calcium leak from the sarcoplasmic reticulum under conditions of increased sympathetic stimulation. Genetic testing for RYR2 variants is essential for diagnosis and family screening, as affected individuals require specific management including beta-blockers, exercise restriction, and sometimes implantable cardioverter-defibrillators to prevent sudden death.

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