Reviewed December 2009
What is the official name of the CASQ2 gene?
The official name of this gene is “calsequestrin 2 (cardiac muscle).”
CASQ2 is the gene's official symbol. The CASQ2 gene is also known by other names, listed below.
What is the normal function of the CASQ2 gene?
The CASQ2 gene provides instructions for making a protein called calsequestrin 2. This protein is found in heart (cardiac) muscle cells called myocytes, where it is involved in the storage and transport of positively charged calcium atoms (calcium ions).
Within myocytes, calsequestrin 2 is located in a cell structure called the sarcoplasmic reticulum, which acts as a storage center for calcium ions. Most of these ions are stored by attaching (binding) to calsequestrin 2. This protein also helps regulate a protein called the RYR2 channel, which 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, calcium ions stored by calsequestrin 2 in the sarcoplasmic reticulum are released 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 CASQ2 gene share characteristics with other genes?
The CASQ2 gene belongs to a family of genes called PDI (protein disulfide isomerases).
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 CASQ2 gene related to health conditions?
- catecholaminergic polymorphic ventricular tachycardia - caused by mutations in the CASQ2 gene
At least seven mutations in the CASQ2 gene have been identified in people with catecholaminergic polymorphic ventricular tachycardia (CPVT). Some of these mutations change single protein building blocks (amino acids) in the calsequestrin 2 protein, while other mutations prevent the cell from producing any functional calsequestrin 2. Studies suggest that the altered or missing protein is unable to perform its usual roles in calcium binding within myocytes. A lack of properly functioning calsequestrin 2 may also affect regulation of the RYR2 channel, allowing calcium ions to "leak" out of the sarcoplasmic reticulum. These changes disrupt the careful control of calcium ion flow within myocytes, which can trigger an abnormal heart rhythm in people with CPVT.
Where is the CASQ2 gene located?
Cytogenetic Location: 1p13.1
Molecular Location on chromosome 1: base pairs 115,700,002 to 115,768,804
The CASQ2 gene is located on the short (p) arm of chromosome 1 at position 13.1.
More precisely, the CASQ2 gene is located from base pair 115,700,002 to base pair 115,768,804 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 CASQ2?
You and your healthcare professional may find the following resources about CASQ2 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28CASQ2%5BTIAB%5D%29%20OR%20%28calsequestrin%202%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/114251)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_CASQ2.html)
- HGNC Gene Family: Protein disulfide isomerases (http://www.genenames.org/cgi-bin/genefamilies/set/692)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=1513)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/845)
What other names do people use for the CASQ2 gene or gene products?
- calsequestrin 2, fast-twitch, cardiac muscle
- cardiac calsequestrin 2
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 CASQ2?
muscle cells ;
sarcoplasmic reticulum ;
You may find definitions for these and many other terms in the Genetics Home Reference
- 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)
- di Barletta MR, Viatchenko-Karpinski S, Nori A, Memmi M, Terentyev D, Turcato F, Valle G, Rizzi N, Napolitano C, Gyorke S, Volpe P, Priori SG. Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia. Circulation. 2006 Sep 5;114(10):1012-9. Epub 2006 Aug 14. (http://www.ncbi.nlm.nih.gov/pubmed/16908766?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)
- Katz G, Arad M, Eldar M. Catecholaminergic polymorphic ventricular tachycardia from bedside to bench and beyond. Curr Probl Cardiol. 2009 Jan;34(1):9-43. doi: 10.1016/j.cpcardiol.2008.09.002. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19068246?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)
- Mohamed U, Napolitano C, Priori SG. Molecular and electrophysiological bases of catecholaminergic polymorphic ventricular tachycardia. J Cardiovasc Electrophysiol. 2007 Jul;18(7):791-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17578347?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/845)
- Postma AV, Denjoy I, Hoorntje TM, Lupoglazoff JM, Da Costa A, Sebillon P, Mannens MM, Wilde AA, Guicheney P. Absence of calsequestrin 2 causes severe forms of catecholaminergic polymorphic ventricular tachycardia. Circ Res. 2002 Oct 18;91(8):e21-6. (http://www.ncbi.nlm.nih.gov/pubmed/12386154?dopt=Abstract)
- Terentyev D, Nori A, Santoro M, Viatchenko-Karpinski S, Kubalova Z, Gyorke I, Terentyeva R, Vedamoorthyrao S, Blom NA, Valle G, Napolitano C, Williams SC, Volpe P, Priori SG, Gyorke S. Abnormal interactions of calsequestrin with the ryanodine receptor calcium release channel complex linked to exercise-induced sudden cardiac death. Circ Res. 2006 May 12;98(9):1151-8. Epub 2006 Apr 6. (http://www.ncbi.nlm.nih.gov/pubmed/16601229?dopt=Abstract)
- Valle G, Galla D, Nori A, Priori SG, Gyorke S, de Filippis V, Volpe P. Catecholaminergic polymorphic ventricular tachycardia-related mutations R33Q and L167H alter calcium sensitivity of human cardiac calsequestrin. Biochem J. 2008 Jul 15;413(2):291-303. doi: 10.1042/BJ20080163. (http://www.ncbi.nlm.nih.gov/pubmed/18399795?dopt=Abstract)
- Viatchenko-Karpinski S, Terentyev D, Györke I, Terentyeva R, Volpe P, Priori SG, Napolitano C, Nori A, Williams SC, Györke S. Abnormal calcium signaling and sudden cardiac death associated with mutation of calsequestrin. Circ Res. 2004 Mar 5;94(4):471-7. Epub 2004 Jan 8. (http://www.ncbi.nlm.nih.gov/pubmed/14715535?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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.