Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

RYR2

Reviewed December 2009

What is the official name of the RYR2 gene?

The official name of this gene is “ryanodine receptor 2 (cardiac).”

RYR2 is the gene's official symbol. The RYR2 gene is also known by other names, listed below.

What is the normal function of the RYR2 gene?

The RYR2 gene provides instructions for making a protein called ryanodine receptor 2. This protein is part of a family of ryanodine receptors, which form channels that transport positively charged calcium atoms (calcium ions) within cells.

Channels made with the ryanodine receptor 2 protein are found in heart (cardiac) muscle cells called myocytes. These channels are embedded in the outer membrane of a cell structure called the sarcoplasmic reticulum, which acts as a storage center for calcium ions. The RYR2 channel controls the flow of calcium ions out of the sarcoplasmic reticulum.

For the heart to beat normally, the cardiac muscle must tense (contract) and relax in a coordinated way. This cycle of muscle contraction and relaxation results from the precise control of calcium ions within myocytes. In response to certain signals, the RYR2 channel releases calcium ions from the sarcoplasmic reticulum into the surrounding cell fluid (the cytoplasm). The resulting increase in calcium ion concentration triggers the cardiac muscle to contract, which pumps blood out of the heart. Calcium ions are then transported back into the sarcoplasmic reticulum, and the cardiac muscle relaxes. In this way, the release and reuptake of calcium ions in myocytes produces a regular heart rhythm.

Does the RYR2 gene share characteristics with other genes?

The RYR2 gene belongs to a family of genes called EF-hand domain containing (EF-hand domain containing).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the RYR2 gene related to health conditions?

catecholaminergic polymorphic ventricular tachycardia - caused by mutations in the RYR2 gene

More than 70 mutations in the RYR2 gene have been found to cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Almost all of these mutations change single protein building blocks (amino acids) in the ryanodine receptor 2 protein. These mutations alter the structure and function of the RYR2 channel.

Researchers are uncertain how RYR2 gene mutations lead to ventricular tachycardia, the abnormally fast and irregular heart rhythm (arrhythmia) that is characteristic of CPVT. Some studies have suggested that mutations interfere with the regulation of the RYR2 channel. Other studies have found that the altered RYR2 channel stays open abnormally, allowing calcium ions to "leak" out of the sarcoplasmic reticulum. It is clear that changes in the structure and function of the RYR2 channel disrupt the careful control of calcium ion flow in myocytes, which can trigger an abnormal heart rhythm in people with CPVT.

other disorders - caused by mutations in the RYR2 gene

Several other mutations in the RYR2 gene have been found to cause a heart condition called arrhythmogenic right ventricular cardiomyopathy (ARVC). This condition causes part of the heart muscle to break down over time, which increases the risk of arrhythmia and sudden death.

The RYR2 gene mutations responsible for ARVC change single amino acids in the ryanodine receptor 2 protein. These mutations alter the structure of the RYR2 channel, which probably allows calcium ions to "leak" out of the sarcoplasmic reticulum. This failure of calcium regulation within myocytes can trigger the abnormal heart rhythm characteristic of ARVC.

Where is the RYR2 gene located?

Cytogenetic Location: 1q43

Molecular Location on chromosome 1: base pairs 237,042,209 to 237,833,987

The RYR2 gene is located on the long (q) arm of chromosome 1 at position 43.

The RYR2 gene is located on the long (q) arm of chromosome 1 at position 43.

More precisely, the RYR2 gene is located from base pair 237,042,209 to base pair 237,833,987 on chromosome 1.

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 RYR2?

You and your healthcare professional may find the following resources about RYR2 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 RYR2 gene or gene products?

  • ARVC2
  • ARVD2
  • cardiac muscle ryanodine receptor
  • cardiac muscle ryanodine receptor-calcium release channel
  • CPVT1
  • VTSIP

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 RYR2?

acids ; arrhythmia ; calcium ; cardiac ; cardiomyopathy ; cell ; channel ; contraction ; cytoplasm ; gene ; ions ; muscle cells ; myocytes ; protein ; receptor ; sarcoplasmic reticulum ; tachycardia

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Bhuiyan ZA, van den Berg MP, van Tintelen JP, Bink-Boelkens MT, Wiesfeld AC, Alders M, Postma AV, van Langen I, Mannens MM, Wilde AA. Expanding spectrum of human RYR2-related disease: new electrocardiographic, structural, and genetic features. Circulation. 2007 Oct 2;116(14):1569-76. Epub 2007 Sep 17. (http://www.ncbi.nlm.nih.gov/pubmed/17875969?dopt=Abstract)
  • Cerrone M, Napolitano C, Priori SG. Catecholaminergic polymorphic ventricular tachycardia: A paradigm to understand mechanisms of arrhythmias associated to impaired Ca(2+) regulation. Heart Rhythm. 2009 Nov;6(11):1652-9. doi: 10.1016/j.hrthm.2009.06.033. Epub 2009 Jun 30. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19879546?dopt=Abstract)
  • Györke S. Molecular basis of catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm. 2009 Jan;6(1):123-9. doi: 10.1016/j.hrthm.2008.09.013. Epub 2008 Sep 16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19121813?dopt=Abstract)
  • Liu N, Priori SG. Disruption of calcium homeostasis and arrhythmogenesis induced by mutations in the cardiac ryanodine receptor and calsequestrin. Cardiovasc Res. 2008 Jan 15;77(2):293-301. Epub 2007 Aug 14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18006488?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6262)
  • Paavola J, Viitasalo M, Laitinen-Forsblom PJ, Pasternack M, Swan H, Tikkanen I, Toivonen L, Kontula K, Laine M. Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves. Eur Heart J. 2007 May;28(9):1135-42. Epub 2007 Mar 8. (http://www.ncbi.nlm.nih.gov/pubmed/17347175?dopt=Abstract)
  • Postma AV, Denjoy I, Kamblock J, Alders M, Lupoglazoff JM, Vaksmann G, Dubosq-Bidot L, Sebillon P, Mannens MM, Guicheney P, Wilde AA. Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients. J Med Genet. 2005 Nov;42(11):863-70. (http://www.ncbi.nlm.nih.gov/pubmed/16272262?dopt=Abstract)
  • Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, Sorrentino V, Danieli GA. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation. 2001 Jan 16;103(2):196-200. (http://www.ncbi.nlm.nih.gov/pubmed/11208676?dopt=Abstract)
  • Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F, Larderet G, Brahmbhatt B, Brown K, Bauce B, Muriago M, Basso C, Thiene G, Danieli GA, Rampazzo A. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001 Feb 1;10(3):189-94. (http://www.ncbi.nlm.nih.gov/pubmed/11159936?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: December 2009
Published: July 28, 2014