Reviewed May 2010
What is the official name of the PKP2 gene?
The official name of this gene is “plakophilin 2.”
PKP2 is the gene's official symbol. The PKP2 gene is also known by other names, listed below.
What is the normal function of the PKP2 gene?
The PKP2 gene provides instructions for making a protein called plakophilin 2. This protein is found primarily in cells of the myocardium, which is the muscular wall of the heart. Within these cells, plakophilin 2 is one of several proteins that make up structures called desmosomes. These structures form junctions that attach cells to one another. Desmosomes provide strength to the myocardium and are involved in signaling between neighboring cells.
How are changes in the PKP2 gene related to health conditions?
- arrhythmogenic right ventricular cardiomyopathy - caused by mutations in the PKP2 gene
More than 50 mutations in the PKP2 gene have been identified in people with arrhythmogenic right ventricular cardiomyopathy (ARVC). This condition most commonly affects the myocardium surrounding the right ventricle, one of the two lower chambers of the heart. ARVC increases the risk of an abnormal heartbeat (arrhythmia) and sudden death.
Some PKP2 gene mutations lead to the production of an abnormally short version of plakophilin 2. Other mutations alter the structure of plakophilin 2 by adding, deleting, or changing one or more of its protein building blocks (amino acids). Studies suggest that the altered protein impairs the formation and function of desmosomes.
Without normal desmosomes, cells of the myocardium detach from one another and die, particularly when the heart muscle is placed under stress (such as during vigorous exercise). The damaged myocardium is gradually replaced by fat and scar tissue. As this abnormal tissue builds up, the walls of the right ventricle become stretched out, preventing the heart from pumping blood effectively. These changes also disrupt the electrical signals that control the heartbeat, which can lead to arrhythmia.
Where is the PKP2 gene located?
Cytogenetic Location: 12p11
Molecular Location on chromosome 12: base pairs 32,790,746 to 32,896,846
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/5318))
The PKP2 gene is located on the short (p) arm of chromosome 12 at position 11.
More precisely, the PKP2 gene is located from base pair 32,790,746 to base pair 32,896,846 on chromosome 12.
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 PKP2?
You and your healthcare professional may find the following resources about PKP2 helpful.
Educational resources - Information pages
- Molecular Biology of the Cell (fourth edition, 2002): Desmosomes Connect Intermediate Filaments from Cell to Cell (http://www.ncbi.nlm.nih.gov/books/NBK26857/)
- Molecular Cell Biology (first edition, 2000): Desmosomes (http://www.ncbi.nlm.nih.gov/books/NBK21599/)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1131)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for PKP2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=5318%5Bgeneid%5D)
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%28PKP2%5BTIAB%5D%29%20OR%20%28plakophilin%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%201800%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/602861)
Research Resources - Tools for researchers
- ARVC Genetic Variants Database (http://grenada.lumc.nl/LOVD2/ARVC/home.php?select_db=PKP2)
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_PKP2.html)
- HGNC Gene Family: Armadillo repeat containing (http://www.genenames.org/cgi-bin/genefamilies/set/409)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=9024)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5318)
What other names do people use for the PKP2 gene or gene products?
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 PKP2?
intermediate filaments ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Bass-Zubek AE, Hobbs RP, Amargo EV, Garcia NJ, Hsieh SN, Chen X, Wahl JK 3rd, Denning MF, Green KJ. Plakophilin 2: a critical scaffold for PKC alpha that regulates intercellular junction assembly. J Cell Biol. 2008 May 19;181(4):605-13. doi: 10.1083/jcb.200712133. Epub 2008 May 12. (http://www.ncbi.nlm.nih.gov/pubmed/18474624?dopt=Abstract)
- Dalal D, James C, Devanagondi R, Tichnell C, Tucker A, Prakasa K, Spevak PJ, Bluemke DA, Abraham T, Russell SD, Calkins H, Judge DP. Penetrance of mutations in plakophilin-2 among families with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol. 2006 Oct 3;48(7):1416-24. Epub 2006 Sep 12. (http://www.ncbi.nlm.nih.gov/pubmed/17010805?dopt=Abstract)
- Dalal D, Molin LH, Piccini J, Tichnell C, James C, Bomma C, Prakasa K, Towbin JA, Marcus FI, Spevak PJ, Bluemke DA, Abraham T, Russell SD, Calkins H, Judge DP. Clinical features of arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in plakophilin-2. Circulation. 2006 Apr 4;113(13):1641-9. Epub 2006 Mar 20. (http://www.ncbi.nlm.nih.gov/pubmed/16549640?dopt=Abstract)
- Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse-Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E, Thierfelder L. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet. 2004 Nov;36(11):1162-4. Epub 2004 Oct 17. Erratum in: Nat Genet. 2005 Jan;37(1):106. (http://www.ncbi.nlm.nih.gov/pubmed/15489853?dopt=Abstract)
- Hall C, Li S, Li H, Creason V, Wahl JK 3rd. Arrhythmogenic right ventricular cardiomyopathy plakophilin-2 mutations disrupt desmosome assembly and stability. Cell Commun Adhes. 2009;16(1-3):15-27. doi: 10.1080/15419060903009329. (http://www.ncbi.nlm.nih.gov/pubmed/19533476?dopt=Abstract)
- Joshi-Mukherjee R, Coombs W, Musa H, Oxford E, Taffet S, Delmar M. Characterization of the molecular phenotype of two arrhythmogenic right ventricular cardiomyopathy (ARVC)-related plakophilin-2 (PKP2) mutations. Heart Rhythm. 2008 Dec;5(12):1715-23. doi: 10.1016/j.hrthm.2008.09.009. Epub 2008 Sep 6. (http://www.ncbi.nlm.nih.gov/pubmed/19084810?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5318)
- Syrris P, Ward D, Asimaki A, Sen-Chowdhry S, Ebrahim HY, Evans A, Hitomi N, Norman M, Pantazis A, Shaw AL, Elliott PM, McKenna WJ. Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy. Circulation. 2006 Jan 24;113(3):356-64. Epub 2006 Jan 16. (http://www.ncbi.nlm.nih.gov/pubmed/16415378?dopt=Abstract)
- van Tintelen JP, Entius MM, Bhuiyan ZA, Jongbloed R, Wiesfeld AC, Wilde AA, van der Smagt J, Boven LG, Mannens MM, van Langen IM, Hofstra RM, Otterspoor LC, Doevendans PA, Rodriguez LM, van Gelder IC, Hauer RN. Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation. 2006 Apr 4;113(13):1650-8. Epub 2006 Mar 27. (http://www.ncbi.nlm.nih.gov/pubmed/16567567?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.