Property Summary

NCBI Gene PubMed Count 78
PubMed Score 125.51
PubTator Score 137.60

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (20)

Disease log2 FC p
urothelial carcinoma -1.400 4.4e-02
Barrett's esophagus 1.500 3.7e-02
psoriasis -1.300 7.7e-04
osteosarcoma -2.624 9.8e-04
cystic fibrosis -3.074 8.0e-07
glioblastoma -1.300 3.7e-04
primitive neuroectodermal tumor -1.200 2.5e-02
intraductal papillary-mucinous adenoma (... 1.500 8.4e-03
intraductal papillary-mucinous carcinoma... 1.800 1.3e-02
intraductal papillary-mucinous neoplasm ... 2.000 1.1e-02
lung cancer 2.700 5.2e-06
interstitial cystitis -2.100 3.1e-04
pediatric high grade glioma -1.100 2.8e-04
atypical teratoid/rhabdoid tumor 1.300 2.4e-02
posterior fossa group A ependymoma 1.200 6.7e-04
lung carcinoma 1.700 3.0e-09
Breast cancer -1.300 2.3e-04
acute myeloid leukemia -1.300 2.4e-03
ovarian cancer -1.500 4.7e-03
pituitary cancer -2.000 2.6e-03

 GWAS Trait (1)

Protein-protein Interaction (6)

Gene RIF (61)

PMID Text
26995964 PKP2 regulates Wnt activity during adipogenic and cardiomyogenic differentiation in arrhythmogenic right ventricular cardiomyopathy.
26321091 Family members - desmosomal mutation carriers who restricted exercise at or below the upper bound of the American Heart Association goal were less likely to be diagnosed and had no Ventricular Tachycardia.
26260507 A heterozygous pathogenic variant in the plakophilin-2 (c.2392A>G, p.T798A) gene was found in an arrhythmogenic LV cardiomyopathy patient and his deceased mother who had had arrhythmogenic cardiomyopathy affecting both ventricles.
25972099 Data suggest juxtamembrane regions/domains of desmocollin-2 (DSC2), plakophilin 2 (PKP2), and plakophilin 3 (PKP3) are involved in desmosome formation in epithelial cells; DSC2 participates in desmosome formation in absence of desmoglein 2 (DSG2).
25936878 Exercise test is valuable for the diagnosis of ARVC in patients with PKP2 gene mutation.
25900994 Case Report: PKP2/DSP mutations in patient with Brugada syndrome and ventricular tachycardia.
25889434 Plakofilin2 mutation plays an important role in the pathogenesis of Brugada syndrome.
25857910 The introduction of the PKP2 R735X mutation into mice resulted in an exercise-dependent arrhythmogenic right ventricular cardiomyopathy.
25786693 Extreme variability in clinical penetrance for a splice-site PKP2 mutation was found in a Bangladeshi family. Some family members were affected by arrhythmogenic right ventricular cardiomyopathy, and some are asymptomatic.
25398255 Currently, 13 genes have been associated with the disease but nearly 40 % of clinically diagnosed cases remain without a genetic diagnosis.
25113560 PKP2 is a novel activator of the EGFR signaling pathway.
25087486 Six variants of uncertain clinical significance in the PKP2, JUP, and DSG2 genes showed a deleterious effect on mRNA splicing, indicating these are ARVD/C-related pathogenic splice site mutations.
24967631 mutations in PKP2 are associated with a later age of onset of arrhythmogenic right ventricular cardiomyopathy
24704780 PKP2 haploinsufficiency contributes to pathogenesis in arrhythmogenic cardiomyopathy.
24352520 Missense mutations in plakophilin-2 cause sodium current deficit and associate with a Brugada syndrome phenotype.
24276085 Downstream Hippo molecules STE20-like protein kinases 1/2, large tumor suppressor kinases 1/2, and Yes-associated protein (YAP, the effector of the pathway) are phosphorylated, offering novel mechanisms for arrhythmogenic cardiomyopathy pathogenesis.
23884246 These data uncover a potential role for PKP2 upstream of beta1 integrin and RhoA in integrating cell-cell and cell-substrate contact signaling in basal keratinocytes.
23651034 Of a total of 715 Sudden cardiac death cases, seven (1.0%) carried one of the ten mutations assayed: three carried KCNH2 R176W, one KCNH2 L552S, two PKP2 Q59L, and one RYR2 R3570W.
23486541 The copy number variations analysis identified a heterozygous deletion of about 122 kb on chromosome 12p11.21, including the entire plakophilin-2 gene and shared by all affected family members.
23270881 PKP2 gene mutation is associated with arrhythmogenic cardiomyopathy in a large Dutch family.
23147395 Results show that PKP2 mutations are insufficient to cause ARVD due to variable expression and incomplete penetrance
22781308 haploinsufficiency is the most likely cause for the genesis of dominant arrhythmogenic right ventricular cardiomyopathy due to mutations in PKP2
22170284 While many of the reported ARVC mutations are truncating mutations, the possibly damaging variant found in this family, is a missense alteration affecting a highly conserved residue 506 located in exon 7.
22119253 PKP2 gene upregulation is associated with bladder cancer invasion.
22035158 The authors report on a pedigree of cases involving a mutation in the plakophilin 2 gene that was associated with the development of arrhythmogenic right ventricular cardiomyopathy.
22019812 PKP2 mutations are not specific for arrhythmogenic right ventricular cardiomyopathy and may result in sudden unexpected death with negative autopsy.
21947748 In breast cancer, compared with normal tissue, PKP1 and PKP2 expressions were indifferent (P > 0.05), but PKP3 expression was significantly increased
21378009 PKP2A was shown to be the major isoform expressed in human heart tissue and PKP2B protein was undetectable; results strongly suggest that p.Arg490Trp and other variants located in PKP2 exon 6 may not be disease causing
20864495 Studies identified two mutations in DSG2, four in DSC2, two in DSP, four in JUP and seven in PKP2.
20693980 Adherens junctions connecting cardiac myxoma cells show exactly such general acquisition of Pkp2.
20554761 Data suggest that PKP2 may functionally link RhoA- and PKC-dependent pathways to drive actin reorganization.
20400443 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20215590 Observational study of genetic testing. (HuGE Navigator)
20031617 Observational study of gene-disease association. (HuGE Navigator)
20031616 Observational study of gene-disease association. (HuGE Navigator)
19955750 Fifteen percent of Danish arrhythmogenic right ventricular cardiomyopathy/dysplasia patients carried PKP2 mutations.
19955750 Observational study of gene-disease association. (HuGE Navigator)
19880068 mutations in plakophylin-2 (PKP2) gene in ARVC
19880068 Observational study of gene-disease association. (HuGE Navigator)
19863551 Observational study of genetic testing. (HuGE Navigator)
19551809 massive acquisition of Pkp2 and its integration into adherens junctions (AJ) plaques of a large number of transformed cell lines is demonstrated with biochemical and immunolocalization techniques.
19533476 Mutant plakophilin-2 proteins were unable to disrupt established desmosomes when expressed in an E-cadherin-expressing epithelial cell model; they were unable to initiate de novo assembly of desmosomes in an N-cadherin-expressing epithelial cell model.
19427443 Direct sequencing of PKP2 led to the identification of 5 novel heterozygous mutations (R158K, Q211X, L419S, A793D, and N852fsX930) in 39% of patients (7 of 18) with ARVD/C.
19427443 Observational study of gene-disease association. (HuGE Navigator)
19302745 Data discovered a plakophilin-2 mutation that prolongs the QT interval dispersion in the southern Chinese Arrhythmogenic right ventricular cardiomyopathy population.
19302745 Observational study of gene-disease association. (HuGE Navigator)
19084810 Their expression did not disrupt localization of endogenous PKP2, connexin-43 (Cx43), or desmoplakin (DP). However, we observed reduced abundance of Cx43 after R79x expression.
18662195 Reduced connexin43 expression and localization to the intercalated disk occurs in heterozygous human PKP-2 mutations, potentially explaining the delayed conduction and propensity to develop arrhythmias seen in this disease.
18632414 Mutations in the desmosome genes were identified in four of the five patients (three with a DSG2 mutation and one with a DSP mutation). Five gene mutations were noted in four patients and all mutations were novel (one patient had a DSG2 double mutation).
18596851 Observational study of gene-disease association. (HuGE Navigator)
18474624 PKP2 knockdown is accompanied by increased phosphorylation of PKC substrates, raising the possibility that global alterations in PKC signaling may contribute to pathogenesis of congenital defects caused by PKP2 deficiency.
17521752 The present study adds to the growing body of evidence that plakophilin-2 missense mutations represent a major inherited cause of arrhythmogenic right ventricular dysplasia (ARVD) in patients of Finnish ancestry.
17041889 Novel homozygous mutation in PKP2 (c.[2484C>T]+[2484C>T]), which is predicted to be translationally silent, produced an alternatively spliced variant and Arrhytmogenic right ventricular dysplasia.
17010805 PKP2 mutations in a group of families with ARVD/C have both reduced penetrance and variable expressivity. Gender may have an influence on penetrance of PKP2 mutations, with male mutation carriers more likely to develop specific phenotypic manifestations
16876743 Premature truncation of the plakophilin-2 protein appears to be the predominant mechanism whereby PKP2 mutations elicit the arrhythmogenic right ventricular cardiomyopathy phenotype.
16567567 PKP2 mutations can be identified in nearly half of the Dutch patients fulfilling the arrhythmogenic right ventricular dysplasia/cardiomyopathy(ARVC)criteria.
16549640 PKP2 mutation in arrhythmogenic right ventricular dysplasia/cardiomyopathy(ARVD/C) correlates with earlier onset of symptoms and arrhythmia. Patients experience implanted cardioverter/defibrillator(ICD) interventions irrespective of classic risk factors.
16415378 mutations in the desmosomal plakophilin-2 gene can cause arrhythmogenic right ventricular cardiomyopathy
15489853 In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome.
11790773 Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta -catenin signaling
9721216 This paper incorrectly maps the locus to 12p13. A later paper by the primary authors corrects the map location to 12p11 (PMID:10828611).

AA Sequence

MAAPGAPAEYGYIRTVLGQQILGQLDSSSLALPSEAKLKLAGSSGRGGQTVKSLRIQEQVQQTLARKGRS      1 - 70
SVGNGNLHRTSSVPEYVYNLHLVENDFVGGRSPVPKTYDMLKAGTTATYEGRWGRGTAQYSSQKSVEERS     71 - 140
LRHPLRRLEISPDSSPERAHYTHSDYQYSQRSQAGHTLHHQESRRAALLVPPRYARSEIVGVSRAGTTSR    141 - 210
QRHFDTYHRQYQHGSVSDTVFDSIPANPALLTYPRPGTSRSMGNLLEKENYLTAGLTVGQVRPLVPLQPV    211 - 280
TQNRASRSSWHQSSFHSTRTLREAGPSVAVDSSGRRAHLTVGQAAAGGSGNLLTERSTFTDSQLGNADME    281 - 350
MTLERAVSMLEADHMLPSRISAAATFIQHECFQKSEARKRVNQLRGILKLLQLLKVQNEDVQRAVCGALR    351 - 420
NLVFEDNDNKLEVAELNGVPRLLQVLKQTRDLETKKQITDHTVNLRSRNGWPGAVAHACNPSTLGGQGGR    421 - 490
ITRSGVRDQPDQHGLLWNLSSNDKLKNLMITEALLTLTENIIIPFSGWPEGDYPKANGLLDFDIFYNVTG    491 - 560
CLRNMSSAGADGRKAMRRCDGLIDSLVHYVRGTIADYQPDDKATENCVCILHNLSYQLEAELPEKYSQNI    561 - 630
YIQNRNIQTDNNKSIGCFGSRSRKVKEQYQDVPMPEEKSNPKGVEWLWHSIVIRMYLSLIAKSVRNYTQE    631 - 700
ASLGALQNLTAGSGPMPTSVAQTVVQKESGLQHTRKMLHVGDPSVKKTAISLLRNLSRNLSLQNEIAKET    701 - 770
LPDLVSIIPDTVPSTDLLIETTASACYTLNNIIQNSYQNARDLLNTGGIQKIMAISAGDAYASNKASKAA    771 - 840
SVLLYSLWAHTELHHAYKKAQFKKTDFVNSRTAKAYHSLKD                                 841 - 881
//

Text Mined References (89)

PMID Year Title
26995964 2015 [THE EFFECT OF PLAKOPHILIN-2 GENE MUTATIONS ON ACTIVITY OF THE CANONICAL Wnt SIGNALING PATHWAY].
26321091 2016 Safety of American Heart Association-recommended minimum exercise for desmosomal mutation carriers.
26260507 2015 Arrhythmogenic Left Ventricular Cardiomyopathy: Suspected by Cardiac Magnetic Resonance Imaging, Confirmed by Identification of a Novel Plakophilin-2 Variant.
25972099 2015 Desmocollin-2 alone forms functional desmosomal plaques, with the plaque formation requiring the juxtamembrane region and plakophilins.
25936878 2015 Epsilon wave uncovered by exercise test in a patient with desmoplakin-positive arrhythmogenic right ventricular cardiomyopathy.
25900994 2015 Epicardial Ventricular Tachycardia Ablation in a Patient With Brugada ECG Pattern and Mutation of PKP2 and DSP Genes.
25889434 2015 Is Brugada syndrome a variant of arrhythmogenic cardiomyopathy?
25857910 2015 Exercise triggers ARVC phenotype in mice expressing a disease-causing mutated version of human plakophilin-2.
25786693 2015 Extreme variability in clinical penetrance for a splice-site Plakophilin-2 mutation in a Bangladeshi family.
25468996 2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
25416956 2014 A proteome-scale map of the human interactome network.
25398255 2015 Clinical interpretation of genetic variants in arrhythmogenic right ventricular cardiomyopathy.
25113560 2014 Plakophilin-2 promotes tumor development by enhancing ligand-dependent and -independent epidermal growth factor receptor dimerization and activation.
25087486 2014 Functional assessment of potential splice site variants in arrhythmogenic right ventricular dysplasia/cardiomyopathy.
24967631 2014 Stop-gain mutations in PKP2 are associated with a later age of onset of arrhythmogenic right ventricular cardiomyopathy.
24704780 2014 Truncating plakophilin-2 mutations in arrhythmogenic cardiomyopathy are associated with protein haploinsufficiency in both myocardium and epidermis.
24352520 2014 Missense mutations in plakophilin-2 cause sodium current deficit and associate with a Brugada syndrome phenotype.
24276085 2014 The hippo pathway is activated and is a causal mechanism for adipogenesis in arrhythmogenic cardiomyopathy.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24129315 2014 Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.
23884246 2014 Plakophilin 2 affects cell migration by modulating focal adhesion dynamics and integrin protein expression.
23863954 2013 Homozygous founder mutation in desmocollin-2 (DSC2) causes arrhythmogenic cardiomyopathy in the Hutterite population.
23651034 2013 Prevalence of arrhythmia-associated gene mutations and risk of sudden cardiac death in the Finnish population.
23486541 2013 Identification of a PKP2 gene deletion in a family with arrhythmogenic right ventricular cardiomyopathy.
23270881 2013 Left-dominant arrhythmogenic cardiomyopathy in a large family: associated desmosomal or nondesmosomal genotype?
23251661 2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23147395 2012 Clinical and genetic characterization of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy caused by a plakophilin-2 splice mutation.
23136403 2013 Mutations in the area composita protein ?T-catenin are associated with arrhythmogenic right ventricular cardiomyopathy.
22889254 2013 Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy.
22781308 2012 Molecular insights into arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 missense mutations.
22170284 2012 A novel variant in plakophilin-2 gene detected in a family with arrhythmogenic right ventricular cardiomyopathy.
22119253 2012 Up-regulation of plakophilin-2 and Down-regulation of plakophilin-3 are correlated with invasiveness in bladder cancer.
22035158 2012 Novel plakophilin2 mutation: three-generation family with arrhythmogenic right ventricular cardiomyopathy.
22019812 2012 PKP2 mutations in sudden death from arrhythmogenic right ventricular cardiomyopathy (ARVC) and sudden unexpected death with negative autopsy (SUDNA).
21947748 2012 Expression of Plakophilins (PKP1, PKP2, and PKP3) in breast cancers.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21378009 2011 Plakophilin 2A is the dominant isoform in human heart tissue: consequences for the genetic screening of arrhythmogenic right ventricular cardiomyopathy.
21062920 2011 Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy caused by desmocollin-2 mutations.
20864495 2010 Wide spectrum of desmosomal mutations in Danish patients with arrhythmogenic right ventricular cardiomyopathy.
20859650 2011 E-cadherin and plakoglobin recruit plakophilin3 to the cell border to initiate desmosome assembly.
20693980 2010 A novel kind of tumor type-characteristic junction: plakophilin-2 as a major protein of adherens junctions in cardiac myxomata.
20554761 2010 Plakophilin 2 couples actomyosin remodeling to desmosomal plaque assembly via RhoA.
20400443 2010 Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice.
20215590 2010 Arrhythmogenic right ventricular dysplasia/cardiomyopathy diagnostic task force criteria: impact of new task force criteria.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20031617 2009 Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy.
20031616 2009 Desmoglein-2 and desmocollin-2 mutations in dutch arrhythmogenic right ventricular dysplasia/cardiomypathy patients: results from a multicenter study.
19955750 2010 Missense variants in plakophilin-2 in arrhythmogenic right ventricular cardiomyopathy patients--disease-causing or innocent bystanders?
19880068 2009 Clinical features, survival experience, and profile of plakophylin-2 gene mutations in participants of the arrhythmogenic right ventricular cardiomyopathy registry of South Africa.
19863551 2010 Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia.
19551809 2009 Upregulation of plakophilin-2 and its acquisition to adherens junctions identifies a novel molecular ensemble of cell-cell-attachment characteristic for transformed mesenchymal cells.
19533476 2009 Arrhythmogenic right ventricular cardiomyopathy plakophilin-2 mutations disrupt desmosome assembly and stability.
19427443 2009 Mutations of plakophilin-2 in Chinese with arrhythmogenic right ventricular dysplasia/cardiomyopathy.
19369195 2009 Large-scale proteomics analysis of the human kinome.
19302745 2009 Mutation of plakophilin-2 gene in arrhythmogenic right ventricular cardiomyopathy.
19084810 2008 Characterization of the molecular phenotype of two arrhythmogenic right ventricular cardiomyopathy (ARVC)-related plakophilin-2 (PKP2) mutations.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18662195 2009 Abnormal connexin43 in arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 mutations.
18632414 2008 Arrhythmogenic right ventricular dysplasia: clinical characteristics and identification of novel desmosome gene mutations.
18596851 2008 Arrhythmogenic right ventricular dysplasia.
18474624 2008 Plakophilin 2: a critical scaffold for PKC alpha that regulates intercellular junction assembly.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17980246 2007 Role of genetic analysis in the management of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy.
17525332 2007 ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.
17521752 2008 Plakophilin-2 missense mutations in arrhythmogenic right ventricular cardiomyopathy.
17041889 2006 Recessive arrhythmogenic right ventricular dysplasia due to novel cryptic splice mutation in PKP2.
17010805 2006 Penetrance of mutations in plakophilin-2 among families with arrhythmogenic right ventricular dysplasia/cardiomyopathy.
16876743 2006 Arrhythmogenic right ventricular cardiomyopathy due to a novel plakophilin 2 mutation: wide spectrum of disease in mutation carriers within a family.
16567567 2006 Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy.
16549640 2006 Clinical features of arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in plakophilin-2.
16541075 2006 The finished DNA sequence of human chromosome 12.
16415378 2006 Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15489853 2004 Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15324660 2004 Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization.
15231748 2004 Functional proteomics mapping of a human signaling pathway.
12941695 2003 Functional analysis of C-TAK1 substrate binding and identification of PKP2 as a new C-TAK1 substrate.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11790773 2002 Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta -catenin signaling.
11416169 2001 Nuclear particles containing RNA polymerase III complexes associated with the junctional plaque protein plakophilin 2.
10852826 2000 Interaction of plakophilins with desmoplakin and intermediate filament proteins: an in vitro analysis.
10828611 2000 Assignment of the plakophilin-2 gene (PKP2) and a plakophilin-2 pseudogene (PKP2P1) to human chromosome bands 12p11 and 12p13, respectively, by in situ hybridization.
10374265 1999 Plakophilin 3--a novel cell-type-specific desmosomal plaque protein.
10374264 1999 Desmosomal plakophilin 2 as a differentiation marker in normal and malignant tissues.
9721216 1998 Chromosomal mapping of human armadillo genes belonging to the p120(ctn)/plakophilin subfamily.
8922383 1996 Plakophilins 2a and 2b: constitutive proteins of dual location in the karyoplasm and the desmosomal plaque.