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CASQ2 gene

calsequestrin 2
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Normal Function

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.

Health Conditions Related to Genetic Changes

Catecholaminergic polymorphic ventricular tachycardia

At least 30 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.

More About This Health Condition

Other Names for This Gene

  • calsequestrin 2 (cardiac muscle)
  • calsequestrin 2, fast-twitch, cardiac muscle
  • cardiac calsequestrin 2
  • CASQ2_HUMAN
  • PDIB2

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • Wang Q, Michalak M. Calsequestrin. Structure, function, and evolution. Cell Calcium. 2020 Sep;90:102242. doi: 10.1016/j.ceca.2020.102242. Epub 2020 Jun 20. Citation on PubMed
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