RYR1
Ryanodine Receptor 1
Gene Summary
RefSeq / NCBIThis gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
Clinical Phenotype
Malignant hyperthermia susceptibility (MHS), central core disease, multiminicore myopathy, and centronuclear myopathy. The most genetically heterogeneous congenital myopathy gene.
Molecular Mechanism
RYR1 encodes the sarcoplasmic reticulum calcium release channel. Gain-of-function dominant mutations → uncontrolled Ca²⁺ release, malignant hyperthermia. Loss-of-function recessive mutations → structural congenital myopathy with cores on biopsy.
Clinical Hallmarks & Key Evidence
Malignant hyperthermia (MH) is a pharmacogenetic emergency triggered by volatile anesthetics (halothane, sevoflurane) or succinylcholine — not by stress or fever alone.
Rosenberg H et al. Orphanet J Rare Dis. 2007;2:21.
Central core disease shows type 1 fiber predominance and central cores (areas devoid of oxidative enzyme activity) on NADH-TR stain — the histologic hallmark.
Jungbluth H. Orphanet J Rare Dis. 2007;2:25.
Dantrolene, which blocks RYR1-mediated Ca²⁺ release, is the specific antidote for MH crisis; it must be available in any facility using volatile anesthetics.
Gronert GA. Anesthesiology. 1980;53(5):395-423.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.