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GeneBe

PKP2

plakophilin 2, the group of Plakophilins|Armadillo repeat containing

Basic information

Region (hg38): 12:32790744-32896777

Links

ENSG00000057294 ∙ NCBI:5318 ∙ OMIM:602861 ∙ HGNC:9024 ∙ Uniprot:Q99959 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Brugada syndrome (Limited), mode of inheritance: AD
  • left ventricular noncompaction (Supportive), mode of inheritance: AD
  • arrhythmogenic right ventricular dysplasia 9 (Strong), mode of inheritance: AD
  • arrhythmogenic right ventricular dysplasia 9 (Definitive), mode of inheritance: AD
  • Brugada syndrome 1 (Disputed Evidence), mode of inheritance: AD
  • catecholaminergic polymorphic ventricular tachycardia (Disputed Evidence), mode of inheritance: AD
  • dilated cardiomyopathy (Disputed Evidence), mode of inheritance: AD
  • arrhythmogenic right ventricular cardiomyopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Arrhythmogenic right ventricular dysplasia, familial 9ADCardiovascularDue to risk of severe sequelae including sudden cardiac death, individuals require ICD placement regardless of classic risk factors related to ICD necessity in clinically similar patients without PKP2 variantsCardiovascular15489853; 16549640; 20301310

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PKP2 gene.

  • Arrhythmogenic right ventricular dysplasia 9 (1123 variants)
  • Cardiomyopathy (688 variants)
  • Cardiovascular phenotype (454 variants)
  • not provided (408 variants)
  • not specified (205 variants)
  • Arrhythmogenic right ventricular cardiomyopathy (96 variants)
  • Familial isolated arrhythmogenic right ventricular dysplasia (22 variants)
  • Inborn genetic diseases (17 variants)
  • PKP2-related condition (8 variants)
  • Primary dilated cardiomyopathy (7 variants)
  • Primary familial hypertrophic cardiomyopathy (5 variants)
  • Cardiac arrhythmia (4 variants)
  • Arrhythmogenic right ventricular dysplasia 1 (3 variants)
  • Long QT syndrome (3 variants)
  • Ventricular tachycardia (3 variants)
  • Left ventricular noncompaction (2 variants)
  • Aborted sudden cardiac death (2 variants)
  • Sudden unexplained death (2 variants)
  • Arrhythmogenic ventricular cardiomyopathy (2 variants)
  • Left ventricular noncompaction cardiomyopathy (2 variants)
  • Becker muscular dystrophy (1 variants)
  • Long QT syndrome 1 (1 variants)
  • Left ventricular noncompaction 1 (1 variants)
  • Ventricular fibrillation, paroxysmal familial, type 1 (1 variants)
  • Primary familial dilated cardiomyopathy (1 variants)
  • Ventricular fibrillation (1 variants)
  • Duchenne muscular dystrophy (1 variants)
  • Ventricular tachycardia;AV junctional rhythm (1 variants)
  • Brugada syndrome;Premature ventricular contraction (1 variants)
  • Brugada syndrome (1 variants)
  • Dilated cardiomyopathy 1S (1 variants)
  • Sudden cardiac death (1 variants)
  • Conduction disorder of the heart (1 variants)
  • Hypertrophic cardiomyopathy;Cardiomyopathy (1 variants)
  • Hypertrophic cardiomyopathy (1 variants)
  • Family history of cardiomyopathy (1 variants)
  • Dilated cardiomyopathy 3B (1 variants)
  • Dilated cardiomyopathy 1A (1 variants)
  • Amyloidogenic transthyretin amyloidosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PKP2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
2
clinvar
274
clinvar
1
clinvar
 277
missense
3
clinvar
4
clinvar
644
clinvar
22
clinvar
1
clinvar
 674
nonsense
56
clinvar
13
clinvar
1
clinvar
 70
start loss
1
clinvar
3
clinvar
1
clinvar
 5
frameshift
90
clinvar
56
clinvar
3
clinvar
 149
inframe indel
15
clinvar
 15
splice donor/acceptor (+/-2bp)
12
clinvar
29
clinvar
2
clinvar
 43
splice region
?
    Intron variants in splice region, excluding donor/acceptor (+/-2bp)
1
28
23
2
 54
non coding
?
    UTR, intron and other, non coding variants
1
clinvar
47
clinvar
115
clinvar
44
clinvar
 207
Total 162 106 715 411 46

Highest pathogenic variant AF is 0.0000460

Variants in PKP2

This is a list of pathogenic ClinVar variants found in the PKP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
12-32790822-T-C Arrhythmogenic right ventricular dysplasia 9 Uncertain significance (Jan 13, 2018)308467
12-32790861-C-A Arrhythmogenic right ventricular dysplasia 9 Benign (Jan 12, 2018)308468
12-32790897-C-T Arrhythmogenic right ventricular dysplasia 9 Uncertain significance (Mar 02, 2018)884062
12-32790993-C-T Arrhythmogenic right ventricular dysplasia 9 Benign (Jan 13, 2018)308469
12-32791030-T-A Arrhythmogenic right ventricular dysplasia 9 Likely benign (Jan 13, 2018)884063
12-32791112-TA-T Arrhythmogenic right ventricular cardiomyopathy Likely benign (Jun 14, 2016)308470
12-32791153-C-G Arrhythmogenic right ventricular dysplasia 9 Benign (Jan 13, 2018)308471
12-32791178-G-A Arrhythmogenic right ventricular dysplasia 9 Uncertain significance (Jan 12, 2018)308472
12-32791204-T-C Arrhythmogenic right ventricular cardiomyopathy Uncertain significance (Jun 14, 2016)308473
12-32791224-CA-C Arrhythmogenic right ventricular cardiomyopathy Likely benign (Jun 14, 2016)308474
12-32791228-C-T Arrhythmogenic right ventricular dysplasia 9 Benign (Jan 13, 2018)308475
12-32791265-T-A Arrhythmogenic right ventricular cardiomyopathy Uncertain significance (Jun 14, 2016)308476
12-32791376-C-A Arrhythmogenic right ventricular cardiomyopathy Uncertain significance (Jun 14, 2016)308477
12-32791401-G-A Arrhythmogenic right ventricular cardiomyopathy Uncertain significance (Jun 14, 2016)308478
12-32791462-G-T Arrhythmogenic right ventricular cardiomyopathy Uncertain significance (Jun 14, 2016)308479
12-32791471-G-T Arrhythmogenic right ventricular cardiomyopathy Uncertain significance (Jun 14, 2016)308480
12-32791480-G-T Arrhythmogenic right ventricular dysplasia 9 Benign (Jan 12, 2018)308481
12-32791492-G-T Arrhythmogenic right ventricular dysplasia 9 Uncertain significance (Jan 13, 2018)308482
12-32791514-G-T Arrhythmogenic right ventricular cardiomyopathy Uncertain significance (Jun 14, 2016)308483
12-32791585-G-A Arrhythmogenic right ventricular dysplasia 9 Uncertain significance (Jan 12, 2018)308484
12-32791612-G-A Arrhythmogenic right ventricular dysplasia 9 Benign (Jan 13, 2018)308485
12-32791671-G-C Arrhythmogenic right ventricular cardiomyopathy Uncertain significance (Jun 14, 2016)308486
12-32791741-A-G Arrhythmogenic right ventricular dysplasia 9 Likely benign (Jan 13, 2018)308487
12-32791778-C-T Arrhythmogenic right ventricular dysplasia 9 Likely benign (Jan 13, 2018)308488
12-32791817-T-G Arrhythmogenic right ventricular dysplasia 9 Uncertain significance (Jan 13, 2018)308489

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PKP2protein_codingprotein_codingENST00000070846 14106096
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
3.11e-180.11712563801101257480.000437
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.2135135001.030.00003035724
Missense in Polyphen130135.540.959091684
Synonymous0.2162082120.9810.00001421778
Loss of Function1.253240.60.7880.00000233439

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002820.00266
Ashkenazi Jewish0.0002980.000298
East Asian0.0003260.000326
Finnish0.00009280.0000924
European (Non-Finnish)0.0004060.000360
Middle Eastern0.0003260.000326
South Asian0.0003590.000327
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: May play a role in junctional plaques. {ECO:0000269|PubMed:22781308}.;
Pathway
Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy;EMT transition in Colorectal Cancer;Keratinization;Developmental Biology;EGFR1;Formation of the cornified envelope (Consensus)

Recessive Scores

pRec
0.123

Intolerance Scores

loftool
0.399
rvis_EVS
0.65
rvis_percentile_EVS
84.18

Haploinsufficiency Scores

pHI
0.680
hipred
N
hipred_score
0.435
ghis
0.408

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.732

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Pkp2
Phenotype
mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype;

Zebrafish Information Network

Gene name
pkp2
Affected structure
post-vent region
Phenotype tag
abnormal
Phenotype quality
kinked

Gene ontology

Biological process
desmosome assembly;cell-cell junction assembly;heart development;positive regulation of sodium ion transport;keratinization;adherens junction maintenance;intermediate filament bundle assembly;maintenance of animal organ identity;ventricular cardiac muscle tissue morphogenesis;cornification;protein localization to plasma membrane;cardiac muscle cell action potential involved in contraction;ventricular cardiac muscle cell action potential;cell-cell signaling involved in cardiac conduction;cell communication by electrical coupling involved in cardiac conduction;bundle of His cell-Purkinje myocyte adhesion involved in cell communication;regulation of heart rate by cardiac conduction;cell-cell adhesion;regulation of ventricular cardiac muscle cell action potential
Cellular component
cornified envelope;nucleus;nucleoplasm;cytoplasm;intermediate filament;plasma membrane;cell-cell junction;adherens junction;cell-cell adherens junction;intercalated disc;integral component of membrane;cell junction;desmosome;messenger ribonucleoprotein complex
Molecular function
protein kinase C binding;protein binding;sodium channel regulator activity;intermediate filament binding;protein-containing complex scaffold activity;ion channel binding;alpha-catenin binding;cadherin binding;cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication