RYR1

About RYR1

RYR1 on chromosome 19q13.2 encodes ryanodine receptor 1, the main calcium release channel of the sarcoplasmic reticulum in skeletal muscle. When a nerve signal depolarizes the muscle membrane, RYR1 opens and releases stored calcium, triggering contraction. Variants in RYR1 are the major cause of malignant hyperthermia susceptibility, a pharmacogenetic disorder in which certain volatile anesthetic gases and the muscle relaxant succinylcholine trigger uncontrolled calcium release, leading to muscle rigidity, rapidly rising body temperature, and a potentially life threatening hypermetabolic crisis. Dantrolene, which reduces calcium release from RYR1, transformed survival from these episodes. People with susceptibility usually have no symptoms in daily life. RYR1 variants also cause several congenital myopathies, including central core disease, as well as exertional heat illness and rhabdomyolysis in some people.