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Genetics Home Reference: your guide to understanding genetic conditions
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RYR1

Reviewed July 2010

What is the official name of the RYR1 gene?

The official name of this gene is “ryanodine receptor 1 (skeletal).”

RYR1 is the gene's official symbol. The RYR1 gene is also known by other names, listed below.

What is the normal function of the RYR1 gene?

The RYR1 gene provides instructions for making a protein called ryanodine receptor 1. This protein is part of a family of ryanodine receptors, which form channels that transport positively charged calcium atoms (ions) within cells. Channels made with the ryanodine receptor 1 protein play a critical role in muscles used for movement (skeletal muscles).

For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of positively charged ions, including calcium, into muscle cells.

When muscles are at rest, calcium ions are stored in a cellular structure called the sarcoplasmic reticulum inside each muscle cell. In response to certain signals, the RYR1 channel releases calcium ions from the sarcoplasmic reticulum into the surrounding cell fluid (cytoplasm). The resulting increase in calcium ion concentration stimulates muscle fibers to contract, allowing the body to move. The process by which certain chemical signals trigger muscle contraction is called excitation-contraction (E-C) coupling.

How are changes in the RYR1 gene related to health conditions?

central core disease - caused by mutations in the RYR1 gene

More than 40 mutations in the RYR1 gene have been identified in people with central core disease (CCD). Most of these mutations affect single protein building blocks (amino acids) in critical regions of the ryanodine receptor 1 protein. These mutations change the structure of the RYR1 channel, which alters the normal flow of stored calcium ions within muscle cells. A disruption in calcium ion release prevents muscles from contracting normally, leading to the muscle weakness characteristic of central core disease.

Researchers have proposed two mechanisms to explain how RYR1 gene mutations underlie muscle weakness in people with central core disease. Some genetic changes cause the RYR1 channel to be "leaky," allowing calcium ions to flow slowly but continually out of the sarcoplasmic reticulum. The leaky channels greatly reduce the amount of stored calcium ions. As a result, not enough calcium ions are available in the sarcoplasmic reticulum to trigger muscle contractions. Muscle weakness results from the inability of skeletal muscles to contract appropriately.

Other RYR1 gene mutations change the structure of the RYR1 channel in a way that impedes the normal flow of calcium ions. Although the sarcoplasmic reticulum stores plenty of these ions, the receptor cannot release them in response to the usual signals. Without enough calcium ions flowing out of the sarcoplasmic reticulum at the appropriate time, muscles cannot contract normally and muscle weakness results. This mechanism is known as E-C uncoupling.

congenital fiber-type disproportion - caused by mutations in the RYR1 gene

At least seven mutations in the RYR1 gene have been found to cause congenital fiber-type disproportion. Some mutations change single amino acids in the ryanodine receptor 1 protein. Other RYR1 gene mutations create a premature stop signal in the instructions for making the receptor, resulting in an abnormally short, nonfunctional protein. Researchers suspect that disruption of the RYR1 channel may play a role in the muscle weakness and other features of congenital fiber-type disproportion, although the role of RYR1 gene mutations in this condition is unclear.

multiminicore disease - caused by mutations in the RYR1 gene

Several mutations in the RYR1 gene have been found to cause atypical forms of multiminicore disease. These mutations change single amino acids in the ryanodine receptor 1 protein, which alters the structure and function of the protein. The effects of these changes are unclear. Some mutations may reduce the amount of ryanodine receptor 1 protein produced by the cell or lead to an unstable version of the protein. Other mutations may interfere with the normal regulation of the RYR1 channel. Researchers believe that some RYR1 gene mutations change the shape of the channel in such a way that calcium ions cannot flow through properly. A disruption in calcium ion transport prevents muscles from contracting normally, leading to the muscle weakness characteristic of multiminicore disease.

malignant hyperthermia - increased risk from variations of the RYR1 gene

At least 30 mutations in the RYR1 gene are known to increase the risk of malignant hyperthermia. Most of these mutations change single amino acids in important regions of the ryanodine receptor 1 protein. These mutations alter the structure of the RYR1 channel, causing it to open more easily and close more slowly in response to certain drugs (particularly some anesthetic gases and a type of muscle relaxant used during surgery). As a result, large amounts of calcium ions are released from the sarcoplasmic reticulum within muscle cells. An overabundance of available calcium ions causes skeletal muscles to contract abnormally, which leads to muscle rigidity in people with malignant hyperthermia. An increase in calcium ion concentration within muscle cells also activates processes that generate heat (leading to increased body temperature) and produce excess acid (leading to acidosis).

Many other changes in the RYR1 gene have been described in people with an increased risk of malignant hyperthermia. It is unclear, however, whether these variations are directly related to malignant hyperthermia risk.

Where is the RYR1 gene located?

Cytogenetic Location: 19q13.1

Molecular Location on chromosome 19: base pairs 38,433,699 to 38,587,563

The RYR1 gene is located on the long (q) arm of chromosome 19 at position 13.1.

The RYR1 gene is located on the long (q) arm of chromosome 19 at position 13.1.

More precisely, the RYR1 gene is located from base pair 38,433,699 to base pair 38,587,563 on chromosome 19.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about RYR1?

You and your healthcare professional may find the following resources about RYR1 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the RYR1 gene or gene products?

  • CCD
  • MHS
  • MHS1
  • PPP1R137
  • ryanodine receptor type1
  • RYDR
  • RYR
  • RYR-1
  • RYR1_HUMAN
  • sarcoplasmic reticulum calcium release channel
  • skeletal muscle ryanodine receptor
  • Skeletal muscle-type ryanodine receptor
  • SKRR

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding RYR1?

acidosis ; acids ; atypical ; calcium ; cell ; channel ; congenital ; contraction ; cytoplasm ; gene ; hyperthermia ; increased body temperature ; ions ; ion transport ; muscle cell ; muscle cells ; muscle relaxant ; protein ; receptor ; sarcoplasmic reticulum ; skeletal muscle ; surgery

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (/glossary).

References

  • Avila G. Intracellular Ca2+ dynamics in malignant hyperthermia and central core disease: established concepts, new cellular mechanisms involved. Cell Calcium. 2005 Feb;37(2):121-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15589992?dopt=Abstract)
  • Clarke NF, Waddell LB, Cooper ST, Perry M, Smith RL, Kornberg AJ, Muntoni F, Lillis S, Straub V, Bushby K, Guglieri M, King MD, Farrell MA, Marty I, Lunardi J, Monnier N, North KN. Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion. Hum Mutat. 2010 Jul;31(7):E1544-50. doi: 10.1002/humu.21278. (http://www.ncbi.nlm.nih.gov/pubmed/20583297?dopt=Abstract)
  • Gene Review: Central Core Disease (http://www.ncbi.nlm.nih.gov/books/NBK1391)
  • Gene Review: Malignant Hyperthermia Susceptibility (http://www.ncbi.nlm.nih.gov/books/NBK1146)
  • Gene Review: Multiminicore Disease (http://www.ncbi.nlm.nih.gov/books/NBK1290)
  • Jungbluth H. Central core disease. Orphanet J Rare Dis. 2007 May 15;2:25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17504518?dopt=Abstract)
  • Jungbluth H. Multi-minicore Disease. Orphanet J Rare Dis. 2007 Jul 13;2:31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17631035?dopt=Abstract)
  • Lyfenko AD, Ducreux S, Wang Y, Xu L, Zorzato F, Ferreiro A, Meissner G, Treves S, Dirksen RT. Two central core disease (CCD) deletions in the C-terminal region of RYR1 alter muscle excitation-contraction (EC) coupling by distinct mechanisms. Hum Mutat. 2007 Jan;28(1):61-8. (http://www.ncbi.nlm.nih.gov/pubmed/16958053?dopt=Abstract)
  • Lyfenko AD, Goonasekera SA, Dirksen RT. Dynamic alterations in myoplasmic Ca2+ in malignant hyperthermia and central core disease. Biochem Biophys Res Commun. 2004 Oct 1;322(4):1256-66. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15336973?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6261)
  • Robinson R, Carpenter D, Shaw MA, Halsall J, Hopkins P. Mutations in RYR1 in malignant hyperthermia and central core disease. Hum Mutat. 2006 Oct;27(10):977-89. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16917943?dopt=Abstract)
  • Rossi AE, Dirksen RT. Sarcoplasmic reticulum: the dynamic calcium governor of muscle. Muscle Nerve. 2006 Jun;33(6):715-31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16477617?dopt=Abstract)
  • Treves S, Anderson AA, Ducreux S, Divet A, Bleunven C, Grasso C, Paesante S, Zorzato F. Ryanodine receptor 1 mutations, dysregulation of calcium homeostasis and neuromuscular disorders. Neuromuscul Disord. 2005 Oct;15(9-10):577-87. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16084090?dopt=Abstract)
  • Wu S, Ibarra MC, Malicdan MC, Murayama K, Ichihara Y, Kikuchi H, Nonaka I, Noguchi S, Hayashi YK, Nishino I. Central core disease is due to RYR1 mutations in more than 90% of patients. Brain. 2006 Jun;129(Pt 6):1470-80. Epub 2006 Apr 18. (http://www.ncbi.nlm.nih.gov/pubmed/16621918?dopt=Abstract)
  • Zhou H, Jungbluth H, Sewry CA, Feng L, Bertini E, Bushby K, Straub V, Roper H, Rose MR, Brockington M, Kinali M, Manzur A, Robb S, Appleton R, Messina S, D'Amico A, Quinlivan R, Swash M, Müller CR, Brown S, Treves S, Muntoni F. Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies. Brain. 2007 Aug;130(Pt 8):2024-36. Epub 2007 May 4. (http://www.ncbi.nlm.nih.gov/pubmed/17483490?dopt=Abstract)
  • Zorzato F, Jungbluth H, Zhou H, Muntoni F, Treves S. Functional effects of mutations identified in patients with multiminicore disease. IUBMB Life. 2007 Jan;59(1):14-20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17365175?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2010
Published: May 4, 2015