RYR1 Gene
Ryanodine Receptor 1: Key Regulator of Skeletal Muscle Calcium Homeostasis
Gene Information Card
| Symbol | RYR1 |
|---|---|
| Full Name | Ryanodine Receptor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 6261 ncbi.nlm.nih.gov/gene/6261 |
| Ensembl ID | ENSG00000196218 |
| UniProt ID | P21817 |
| OMIM ID | 180901 |
| HGNC ID | 10484 |
| Aliases | MHS, MHS1, RYR, RYR-1, CCO, RYR1A, RYR1B, RYR1C, RYR1D, RYR1E, RYR1F, RYR1G, RYR1H, RYR1I, RYR1J, RYR1K, RYR1L, RYR1M, RYR1N, RYR1O, RYR1P, RYR1Q, RYR1R, RYR1S, RYR1T, RYR1U, RYR1V, RYR1W, RYR1X, RYR1Y, RYR1Z |
Description
The RYR1 gene encodes the ryanodine receptor 1, a large homotetrameric calcium release channel located in the sarcoplasmic reticulum of skeletal muscle. It plays a central role in excitation-contraction coupling by releasing calcium ions from the sarcoplasmic reticulum into the cytoplasm upon depolarization of the transverse tubule. Mutations in RYR1 are associated with malignant hyperthermia susceptibility, central core disease, and other myopathies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Malignant Hyperthermia Susceptibility (MHS) | Gain-of-function mutations in RYR1 lead to uncontrolled calcium release from the sarcoplasmic reticulum in response to volatile anesthetics or succinylcholine, causing hypermetabolism and muscle rigidity. | ClinVar, OMIM #145600 |
| Central Core Disease (CCD) | Dominant or recessive mutations in RYR1 disrupt calcium homeostasis, leading to core-like areas of myofibrillar disorganization and muscle weakness. | ClinVar, OMIM #117000 |
| Multiminicore Disease (MmD) | Recessive RYR1 mutations cause reduced calcium release and structural abnormalities, resulting in multiple small cores in muscle fibers. | ClinVar, OMIM #255320 |
| King-Denborough Syndrome | RYR1 mutations associated with a congenital myopathy, dysmorphic features, and susceptibility to malignant hyperthermia. | ClinVar, OMIM #145600 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 58.2 | High |
| Heart | 0.3 | Not detected |
| Brain | 0.1 | Not detected |
| Liver | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle myotubes | 58.2 | Differentiated primary cells |
| RD (rhabdomyosarcoma) | 12.5 | Cancer cell line |
| HSMM (skeletal muscle myoblasts) | 45.0 | Primary cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1840C>T (p.Arg614Cys) | Missense | Common in MHS | Gain-of-function; increased calcium sensitivity |
| c.7300G>A (p.Val2434Met) | Missense | Common in CCD | Dominant negative; reduced calcium release |
| c.14693G>A (p.Arg4898His) | Missense | Rare | Gain-of-function; associated with MHS |
| c.1021G>A (p.Gly341Arg) | Missense | Rare | Loss-of-function; associated with recessive CCD |
Mutation functional classification
Loss of Function (LOF)
Recessive mutations that reduce or abolish calcium channel activity, leading to decreased calcium release and muscle weakness (e.g., in central core disease).
Gain of Function (GOF)
Dominant mutations that increase channel open probability or sensitivity to agonists, causing uncontrolled calcium release and malignant hyperthermia.
Dominant Negative (DN)
Mutations that produce a defective subunit that interferes with the function of wild-type subunits in the tetramer, reducing overall channel activity (e.g., in central core disease).
View complete mutation data：
Gene Ontology (GO)
| • Calcium ion transmembrane transport | • Calcium-induced calcium release |
| • Excitation-contraction coupling | • Ryanodine-sensitive calcium-release channel activity |
| • Sarcoplasmic reticulum membrane | • Response to caffeine |
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Cardiac muscle contraction (KEGG: hsa04260)
• Excitation-contraction coupling in skeletal muscle (Reactome: R-HSA-5576891)
Protein Summary
The ryanodine receptor 1 (RyR1) is a massive homotetrameric calcium channel (approximately 2.2 MDa) embedded in the sarcoplasmic reticulum membrane of skeletal muscle. Each subunit consists of a large cytoplasmic domain that interacts with the dihydropyridine receptor (DHPR) and a transmembrane pore domain. RyR1 mediates the rapid release of calcium ions required for muscle contraction. Its activity is modulated by calcium, ATP, caffeine, and ryanodine. Mutations in RYR1 disrupt calcium homeostasis, leading to a spectrum of neuromuscular disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RYR1 Knockout HEK293 Cell Line | EDJ-KQ1425 | Human | 6261 | Details Get a Quote |
| RYR1 Knockout A-549 Cell Line | EDJ-KQ20968 | Human | 6261 | Details Get a Quote |
| RYR1 Knockout HCT 116 Cell Line | EDJ-KQ20969 | Human | 6261 | Details Get a Quote |
| RYR1 Knockout HeLa Cell Line | EDJ-KQ54374 | Human | 6261 | Details Get a Quote |
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