Gene:
RYR1
ryanodine receptor 1 (skeletal)

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.


FDA Label for succinylcholine and BCHE, CACNA1S, RYR1

Summary

Succinylcholine is rapid acting, depolarizing skeletal muscle relaxant indicated as an adjunct to general anesthesia, to facilitate tracheal intubation and mechanical ventilation. The FDA label warns that individuals who are carriers of the atypical variant of the plasma cholinesterase gene (BCHE) are at risk of prolonged apnea if administered succinylcholine, contraindicates succinylcholine in individuals diagnosed with Duchene's or Becker's muscular dystrophy because of risk of rhabdomyolysis, hyperkalemia and cardiac arrest and contraindicates succinylcholine in individuals with a family history of malignant hyperthermia, a potentially fatal hypermetabolic state in skeletal muscle.

Annotation

Annotation

Although the succinylcholine chloride (Anectine) drug label does not specifically mention genetic testing, the FDA highlights that precaution should be taken prior to administering succinylcholine for individuals carrying one of many genetic variants known to increase the risk of:

  • Prolonged apnea
  • Malignant hyperthermia
  • Hyperkalemia

Specific variants in the RYR1 and CACNA1S genes are associated with risk of malignant hyperthermia in individuals administered succinylcholine. The currently accepted standard for testing for susceptibility to malignant hyperthermia is the in vitro contracture test (also known as the caffeine halothane contracture test).

Excerpts from the succinylcholine chloride (Anectine) drug label:


RISK OF CARDIAC ARREST FROM HYPERKALEMIC RHABDOMYOLYSIS
There have been rare reports of acute rhabdomyolysis with hyperkalemia followed by ventricular dysrhythmias, cardiac arrest, and death after the administration of succinylcholine to apparently healthy children who were subsequently found to have undiagnosed skeletal muscle myopathy, most frequently Duchenne's muscular dystrophy.

Succinylcholine is contraindicated in persons with personal or familial history of malignant hyperthermia, skeletal muscle myopathies, and known hypersensitivity to the drug.

WARNINGS
SUCCINYLCHOLINE IS METABOLIZED BY PLASMA CHOLINESTERASE AND SHOULD BE USED WITH CAUTION, IF AT ALL, IN PATIENTS KNOWN TO BE OR SUSPECTED OF BEING HOMOZYGOUS FOR THE ATYPICAL PLASMA CHOLINESTERASE GENE.

Patients homozygous for atypical plasma cholinesterase gene (1 in 2500 patients) are extremely sensitive to the neuromuscular blocking effect of succinylcholine. In these patients, a 5- to 10-mg test dose of succinylcholine may be administered to evaluate sensitivity to succinylcholine, or neuromuscular blockade may be produced by the cautious administration of a 1-mg/mL solution of succinylcholine by slow IV infusion. Apnea or prolonged muscle paralysis should be treated with controlled respiration.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the succinylcholine chloride drug label.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Apnea
    • Warnings section, Pediatric use section, Adverse reactions section, Precautions section, other
    • source: FDA Label
  • Hyperkalemia
    • Boxed warning section, Contraindications section, Pediatric use section, Adverse reactions section, Warnings and precautions section, other
    • source: FDA Label
  • Malignant Hyperthermia
    • Boxed warning section, Contraindications section, Warnings section, Pediatric use section, Adverse reactions section, other
    • source: FDA Label
  • BCHE
    • Adverse reactions section, Warnings and precautions section, other
    • source: FDA Label

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Related Drugs?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs118192161 11203069C>T, 15512C>T, 38934851C>T, 487C>T, Arg163Cys
C > T
Missense
Arg163Cys
No VIP available CA VA
rs118192162 11214217A>C, 11214217A>G, 1565A>C, 1565A>G, 26660A>C, 26660A>G, 38945999A>C, 38945999A>G, Tyr522Cys, Tyr522Ser
A > C
A > G
Missense
Tyr522Ser
Tyr522Cys
No VIP available CA VA
rs118192163 11253423G>A, 11253423G>C, 38985205G>A, 38985205G>C, 6488G>A, 6488G>C, 65866G>A, 65866G>C, Arg2163His, Arg2163Pro
G > C
G > A
Missense
Arg2163Pro
Arg2163His
No VIP available CA VA
rs118192167 11338862A>G, 14372A>G, 14387A>G, 151305A>G, 39070644A>G, Tyr4791Cys, Tyr4796Cys
A > G
Missense
Tyr4796Cys
No VIP available No Clinical Annotations available VA
rs118192168 11339261G>A, 14530G>A, 14545G>A, 151704G>A, 39071043G>A, Val4844Ile, Val4849Ile
G > A
Missense
Val4849Ile
No VIP available CA VA
rs118192170 11343847T>C, 14678T>C, 14693T>C, 156290T>C, 39075629T>C, Ile4893Thr, Ile4898Thr
T > C
Missense
Ile4898Thr
No VIP available CA VA
rs118192172 11216403C>T, 1840C>T, 28846C>T, 38948185C>T, Arg614Cys
C > T
Missense
Arg614Cys
No VIP available CA VA
rs118192175 11253422C>T, 38985204C>T, 6487C>T, 65865C>T, Arg2163Cys
C > T
Missense
Arg2163Cys
No VIP available CA VA
rs118192176 11253437G>A, 38985219G>A, 6502G>A, 65880G>A, Val2168Met
G > A
Missense
Val2168Met
No VIP available CA VA
rs118192177 11255141C>G, 11255141C>T, 38986923C>G, 38986923C>T, 6617C>G, 6617C>T, 67584C>G, 67584C>T, Thr2206Arg, Thr2206Met
C > G
C > T
Missense
Thr2206Met
Thr2206Arg
No VIP available CA VA
rs121918592 1021G>A, 1021G>C, 11207570G>A, 11207570G>C, 20013G>A, 20013G>C, 38939352G>A, 38939352G>C, Gly341Arg
G > C
G > A
Missense
Gly341Arg
No VIP available CA VA
rs121918593 11258851G>A, 38990633G>A, 71294G>A, 7300G>A, Gly2434Arg
G > A
Missense
Gly2434Arg
No VIP available CA VA
rs121918594 11259513G>A, 38991295G>A, 71956G>A, 7373G>A, Arg2458His
G > A
Missense
Arg2458His
No VIP available CA VA
rs121918595 11338952C>T, 14462C>T, 14477C>T, 151395C>T, 39070734C>T, Thr4821Ile, Thr4826Ile
C > T
Missense
Thr4826Ile
No VIP available No Clinical Annotations available VA
rs1801086 11205568G>A, 11205568G>C, 11205568G>M, 18011G>A, 18011G>C, 18011G>M, 38937350G>A, 38937350G>C, 38937350G>M, 742G>A, 742G>C, 742G>M, Gly248Arg, RYR1:ARG248GLY
G > C
G > A
Missense
Gly248Arg
No VIP available No Clinical Annotations available VA
rs193922772 11216404G>T, 1841G>T, 28847G>T, 38948186G>T, Arg614Leu
G > T
G > A
Missense
Arg614Leu
No VIP available No Clinical Annotations available VA
rs193922803 11258528C>T, 38990310C>T, 7063C>T, 70971C>T, Arg2355Trp
C > T
Missense
Arg2355Trp
No VIP available CA VA
rs28933397 11259512C>T, 38991294C>T, 71955C>T, 7372C>T, 7372CT, ARG2458CYS, Arg2458Cys
C > T
Missense
Arg2458Cys
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  None
Alternate Symbols:  RYR
PharmGKB Accession Id: PA34896

Details

Cytogenetic Location: chr19 : q13.2 - q13.2
GP mRNA Boundary: chr19 : 38924340 - 39078204
GP Gene Boundary: chr19 : 38914340 - 39081204
Strand: plus
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.
No related genes are available

Curated Information ?

Evidence Drug Class
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
hmg coa reductase inhibitors

Curated Information ?

Publications related to RYR1: 11

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Functional characterization of 2 known ryanodine receptor mutations causing malignant hyperthermia. Anesthesia and analgesia. 2014. Schiemann Anja H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study. Orphanet journal of rare diseases. 2014. Klingler Werner, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genetic risk for malignant hyperthermia in non-anesthesia-induced myopathies. Molecular genetics and metabolism. 2011. Vladutiu Georgirene D, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Malignant hyperthermia: a pharmacogenetic disorder. Pharmacogenomics. 2008. Stowell Kathryn M. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies. Brain : a journal of neurology. 2007. Zhou Haiyan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
An autosomal dominant congenital myopathy with cores and rods is associated with a neomutation in the RYR1 gene encoding the skeletal muscle ryanodine receptor. Human molecular genetics. 2000. Monnier N, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A novel ryanodine receptor mutation and genotype-phenotype correlation in a large malignant hyperthermia New Zealand Maori pedigree. Human molecular genetics. 2000. Brown R L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Ryanodine receptor mutations in malignant hyperthermia and central core disease. Human mutation. 2000. McCarthy T V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Segregation of malignant hyperthermia, central core disease and chromosome 19 markers. British journal of anaesthesia. 1999. Curran J L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia. Genomics. 1992. Gillard E F, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia. Genomics. 1991. Gillard E F, et al. PubMed

LinkOuts

Entrez Gene:
6261
OMIM:
117000
145600
180901
255320
UCSC Genome Browser:
NM_000540
RefSeq RNA:
NM_000540
NM_001042723
RefSeq Protein:
NP_000531
NP_001036188
MutDB:
RYR1
ALFRED:
LO000292N
HuGE:
RYR1
Comparative Toxicogenomics Database:
6261
ModBase:
P21817
HGNC:
10483

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