AlphaFold predicted structure
PKP2 · Q99959
Mean pLDDT
64.1/ 100
Low
881 residues
Confidence breakdown
- Very high(≥ 90)42%
- Confident(70–90)9%
- Low(50–70)6%
- Very low(< 50)44%
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AlphaFold (Jumper et al., 2021) · CC BY 4.0
PKP2
Chr 12p11.21plakophilin 2
- MANE:
- ENST00000340811.9
Annotations refreshed 1 month ago.
Predicted protein structure
Clinical relevance (Genomics England PanelApp)
Diagnostic Grade (Green)
Arrhythmogenic right ventricular cardiomyopathy
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedDilated and arrhythmogenic cardiomyopathy
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedPaediatric or syndromic cardiomyopathy
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedFetal anomalies
BIALLELIC, autosomal or pseudoautosomalBrugada syndrome and cardiac sodium channel disease
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedDilated Cardiomyopathy and conduction defects
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedHereditary neuropathy
Hereditary neuropathy or pain disorder
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Disease associations (Open Targets)
Arrhythmogenic right ventricular dysplasia
0.84arrhythmogenic right ventricular cardiomyopathy
0.77cardiomyopathy
0.61Abnormality of the cardiovascular system
0.57familial isolated arrhythmogenic right ventricular dysplasia
0.55atrial fibrillation
0.47cardiac arrhythmia
0.47left ventricular noncompaction
0.45ventricular tachycardia
0.43hypertrophic cardiomyopathy
0.43
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Protein function (UniProt)
Plakophilin-2
A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:25208567). Regulates focal adhesion turnover resulting in changes in focal adhesion size, cell adhesion and cell spreading, potentially via transcriptional modulation of beta-integrins (PubMed:23884246). Required to maintain gingival epithelial barrier function (PubMed:34368962). Important component of the desmosome that is also required for localization of desmosome component proteins such as DSC2, DSG2 and JUP to the desmosome cell-cell junction (PubMed:22781308, PubMed:25208567). Required for the formation of desmosome cell junctions in cardiomyocytes, thereby required for the correct formation of the heart, specifically trabeculation and formation of the atria walls (By similarity). Loss of desmosome cell junctions leads to mis-localization of DSP and DSG2 resulting in disruption of cell-cell adhesion and disordered intermediate filaments (By similarity). Modulates profibrotic gene expression in cardiomyocytes via regulation of DSP expression and subsequent activation of downstream TGFB1 and MAPK14/p38 MAPK signaling (By similarity). Required for cardiac sodium current propagation and electrical synchrony in cardiac myocytes, via ANK3 stabilization and modulation of SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). Required for mitochondrial function, nuclear envelope integrity and positive regulation of SIRT3 transcription via maintaining DES localization at its nuclear envelope and cell tip anchoring points, and thereby preserving regulation of the transcriptional program (PubMed:35959657). Maintenance of nuclear envelope integrity protects against DNA damage and transcriptional dysregulation of genes, especially those involved in the electron transport chain, thereby preserving mitochondrial function and protecting against superoxide radical anion generation (PubMed:35959657). Binds single-stranded DNA (ssDNA) (PubMed:20613778). May regulate the localization of GJA1 to gap junctions in intercalated disks of the heart (PubMed:18662195). Involved in the inhibition of viral infection by influenza A viruses (IAV) (PubMed:28169297). Acts as a host restriction factor for IAV viral propagation, potentially via disrupting the interaction of IAV polymerase complex proteins (PubMed:28169297)
Diseases associated with PKP2
Curated MONDO disease pages that list PKP2 among their top associated genes.