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Symbol RYR1 contributors: mct - updated : 31-08-2018
HGNC name ryanodine receptor 1 (skeletal)
HGNC id 10483
Corresponding disease
CCO central core disease of muscle
MHS1 malignant hyperthermia susceptibility, 1
MMDO multiminicore disease with external ophthalmoplegia
Location 19q13.2      Physical location : 38.924.339 - 39.078.203
Synonym name
  • sarcoplasmic reticulum calcium release channel
  • skeletal muscle ryanodine receptor
  • type 1-like ryanodine receptor
  • sarcoplasmic reticulum calcium release channel
  • Synonym symbol(s) HRR, RYR, MHS, RYDR, SKRR
    TYPE functioning gene
    STRUCTURE 153.87 kb     106 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (TATA box)
    Binding site   transcription factor
    text structure five TATA boxes, several transcription activator sites
    MAPPING cloned Y linked Y status confirmed
    Map cen - D19S49 - D19S75 - D19S191 - RYR1 ,D19S378 - D19S18 /D19S190 - D19S47 - qter
    Text see CCO
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    106 - 15391 565 5038 - 2007 17707769
    isoform 1
    105 - 15376 564 5033 - 2007 17707769
  • lacking an alternate in-frame exon, compared to variant 1
  • isoform 2 is shorter than isoform 1
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepharynx   highly
    Respiratoryrespiratory tractlarynx  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunedendritic cell
    Lymphoid/ImmuneT cell Homo sapiens
    cell lineage
    cell lines
    at STAGE
    IMPRINTING maternally
  • N terminal domain D3 involved in calcium dependent regulation of the calcium release channel
  • N-terminal and central domain elements are closely apposed near the FKBP binding site
  • five MIR and RIH domain
  • a central domain of RYR1 is the transducer for long-range allosteric gating of channel opening
  • three SPRY domain, and ASI/basic
  • SPRY2 domain interact in an F loop regulatory module , and SPRY2 domain forms a link between the N-terminal gating ring and the clamp region
  • mono polymer homomer , tetramer
    interspecies homolog to murine Ryr1 (96.00pc)
  • ryanodine receptor family
  • CATEGORY motor/contractile , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • involved in contraction of skeletal muscle triggered by release of calcium ions from sarcoplasmic reticulum following depolarization of transverse tubules
  • with SEPN1, are both required for normal muscle development and differentiation and for some calcium mobilization events in the embryo
  • with SERCA2B (ATP2A2 variant B) is involved in vasodilatation in pulmonary arterial smooth muscle
  • leaky RYR1 contributes to age-related loss of muscle function
  • large, homotetrameric sarcoplasmic reticulum membrane protein that is essential for Ca(2+) cycling in both skeletal and cardiac muscle
  • RYR1, RYR2, RYR3 strongly regulate Ca2+ influx in human T cells
  • RYR1, RYR2, RYR3 are important regulators of Ca2+ signaling and Ca2+-dependent functions in human immune cells, which could be potentially used as a tool for modulating immune responses
  • stabilization of RYR1 might be effective not only in neuronal death but also in neuronal dysfunction of Huntington disease
  • RYR1 release Ca(2+) from the sarcoplasmic reticulum to initiate skeletal muscle contraction
  • role for RYR1 on both the pre- and postsynaptic sides of the neuromuscular junction (NMJ)
  • important non-contractile role of RYR1 or RYR1-mediated Ca(2+) signaling during muscle organ development
  • intracellular calcium channel responsible for rapid release of Ca(2+) from the sarcoplasmic/endoplasmic reticulum (SR/ER) to the cytoplasm, which is essential for the excitation-contraction (E-C) coupling of cardiac and skeletal muscles
  • plays a crucial role in vasoconstriction and hemostasis
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text cellular calcium ion homeostasis
    a component
    small molecule
  • binding SEPN1 (RyR channel is a “redox sensor” regulated by a number of associated proteins including SEPN1)
  • interacting with TRPC3 (TRPC3 and RYR1 are functionally engaged via linker proteins in skeletal muscle)
  • CLIC2 can interact with RYR1 and modulate its channel activity
  • CHERP is an RYR1 interacting protein that may be involved in the regulation of excitation-contraction coupling
  • S100A1 and calmodulin bind to an overlapping domain on the RYR1 to tune the Ca2+ release process, and thereby regulate skeletal muscle function
  • interaction between FKBP1A and RYR1, RYR3 and ITPR1
  • RYR1, RYR2, RYR3 regulate SOCE by controlling Ca2+ store refilling
  • because SOCE regulates a variety of Ca2+-dependent T cell responses, RYR1, RYR2, RYR3 are in a position to control vital T cell functions
  • CAV3 forms a disc-shaped nonamer that binds the Ca(2+)-release channel, RYR1
  • FKBP1A promotes the RYR1 closed state, thereby inhibiting Ca2+ leakage in resting muscle
  • C-terminal domain of ASPH binds to residues including the S1-S2 linker of RYR1 and N-terminal domain of ASPH binds between RYR1 residues 1078 and 2156
  • CALM1 and S100A1 can concurrently bind to and functionally modulate RYR1 and RYR2, but this does not involve direct competition at the RYR CALM binding site
  • cell & other
    Other triggered by the dehydropyridine receptor(s)
    corresponding disease(s) CCO , MHS1 , MMDO
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    altered RYR1 function may contribute to the neurodegeneration in Huntington disease
    constitutional germinal mutation      
    associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome
    Susceptibility to aneurysmatic subarachnoid hemorrhage
    Variant & Polymorphism other
  • rare RYR1 variants in patients suffering from aneurysmatic subarachnoid hemorrhage
  • Candidate gene
    Therapy target
    RyR activity may not be irreversibly damaged in patients with SEPN1-associated disease and might provide a target for therapeutic intervention
    altered RYR function is involved in neuronal cell death, and its stabilization might be beneficial for treatment of Huntington disease (dantrolene or other similar RYR inhibitors may be beneficial for HD patients)