PKP2 Gene: Plakophilin 2
Key Component of Desmosomes and Arrhythmogenic Right Ventricular Cardiomyopathy
Gene Information Card
| Symbol | PKP2 |
|---|---|
| Full Name | Plakophilin 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 12p11.21 |
| NCBI Gene ID | 5318 ncbi.nlm.nih.gov/gene/5318 |
| Ensembl ID | ENSG00000157207 |
| UniProt ID | Q99959 |
| OMIM ID | 602861 |
| HGNC ID | 9024 |
| Aliases | ARVD9, PKP2A, PKP2B |
Description
The PKP2 gene encodes plakophilin 2, a member of the armadillo-repeat protein family and a critical component of desmosomes. Desmosomes are intercellular junctions that provide mechanical strength to tissues, particularly cardiac muscle and epidermis. Plakophilin 2 is essential for desmosome assembly and stability, linking cadherins to intermediate filaments. Mutations in PKP2 are a major cause of arrhythmogenic right ventricular cardiomyopathy (ARVC), a disorder characterized by fibrofatty replacement of the myocardium and life-threatening arrhythmias.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Arrhythmogenic right ventricular cardiomyopathy (ARVC) | Loss-of-function mutations in PKP2 disrupt desmosome integrity, leading to myocyte detachment, cell death, and fibrofatty replacement, predisposing to arrhythmias. | ClinVar, OMIM |
| Sudden cardiac death | PKP2 mutations increase risk of ventricular arrhythmias and sudden death, often in young individuals. | ClinVar, NCBI |
| Naxos disease (associated with other desmosomal genes) | While primarily linked to JUP, PKP2 mutations can contribute to similar cardiocutaneous syndromes. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 27.8 | High |
| Skin | 15.2 | Medium |
| Esophagus | 12.1 | Medium |
| Skeletal muscle | 8.5 | Medium |
| Liver | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPS-derived) | 30.5 | High expression in cardiac cells |
| Keratinocytes | 18.0 | Medium expression in skin cells |
| HeLa | 5.2 | Low expression |
| HEK 293 | 3.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2013delC (p.Lys672Argfs*12) | Frameshift | Common in ARVC | Loss of function |
| c.2489+1G>A | Splice site | Recurrent | Loss of function |
| c.2146-1G>C | Splice site | Rare | Loss of function |
| c.1211dupA (p.Asn404Lysfs*8) | Frameshift | Reported | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most PKP2 mutations are loss-of-function, leading to haploinsufficiency or truncated protein, impairing desmosome assembly and cell adhesion.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PKP2.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type plakophilin 2 function, though loss-of-function is predominant.
View complete mutation data：
Gene Ontology (GO)
| • cell adhesion (GO:0007155) | • cell-cell junction (GO:0005913) |
| • desmosome (GO:0030057) | • intermediate filament (GO:0005882) |
| • protein binding (GO:0005515) |
Pathways
• Cell adhesion molecules (CAMs) - KEGG hsa04514
• Desmosome assembly - Reactome R-HSA-446728
• Arrhythmogenic right ventricular cardiomyopathy - KEGG hsa05412
Protein Summary
Plakophilin 2 is a 797-amino acid protein with armadillo repeats that localizes to desmosomes. It interacts with desmoplakin, plakoglobin, and cadherins, stabilizing cell-cell adhesion. In cardiac muscle, it is crucial for maintaining structural integrity under mechanical stress. Loss of plakophilin 2 leads to desmosome disassembly, myocyte death, and fibrofatty replacement, characteristic of ARVC.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PKP2 Knockout HEK293 Cell Line | EDJ-KQ5473 | Human | 5318 | Details Get a Quote |
| PKP2 Knockout A-549 Cell Line | EDJ-KQ28679 | Human | 5318 | Details Get a Quote |
| PKP2 Knockout HCT 116 Cell Line | EDJ-KQ28680 | Human | 5318 | Details Get a Quote |
| PKP2 Knockout HeLa Cell Line | EDJ-KQ28681 | Human | 5318 | Details Get a Quote |
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