PKP2
Basic information
Region (hg38): 12:32790745-32896798
Links
Phenotypes
GenCC
Source:
- 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:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Arrhythmogenic right ventricular dysplasia, familial 9 | AD | Cardiovascular | Due 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 variants | Cardiovascular | 15489853; 16549640; 20301310 |
ClinVar
This is a list of variants' phenotypes submitted to
- Arrhythmogenic_right_ventricular_dysplasia_9 (1388 variants)
- Cardiomyopathy (735 variants)
- Arrhythmogenic_right_ventricular_cardiomyopathy (715 variants)
- Cardiovascular_phenotype (713 variants)
- not_provided (447 variants)
- not_specified (216 variants)
- PKP2-related_disorder (41 variants)
- Familial_isolated_arrhythmogenic_right_ventricular_dysplasia (29 variants)
- Primary_dilated_cardiomyopathy (7 variants)
- Primary_familial_hypertrophic_cardiomyopathy (5 variants)
- Hypertrophic_cardiomyopathy (5 variants)
- Ventricular_tachycardia (5 variants)
- Sudden_unexplained_death (3 variants)
- Long_QT_syndrome (3 variants)
- Cardiac_arrhythmia (3 variants)
- Left_ventricular_noncompaction_cardiomyopathy (2 variants)
- Left_ventricular_noncompaction (2 variants)
- Brugada_syndrome (2 variants)
- Arrhythmogenic_ventricular_cardiomyopathy (2 variants)
- Dilated_cardiomyopathy_1A (1 variants)
- Premature_ventricular_contraction (1 variants)
- Dilated_cardiomyopathy_3B (1 variants)
- AV_junctional_rhythm (1 variants)
- Amyloidosis,_hereditary_systemic_1 (1 variants)
- Left_ventricular_noncompaction_1 (1 variants)
- Sudden_cardiac_death (1 variants)
- Dilated_cardiomyopathy_1S (1 variants)
- Ventricular_fibrillation,_paroxysmal_familial,_type_1 (1 variants)
- Family_history_of_cardiomyopathy (1 variants)
- Primary_familial_dilated_cardiomyopathy (1 variants)
- Conduction_disorder_of_the_heart (1 variants)
- Long_QT_syndrome_1 (1 variants)
- Becker_muscular_dystrophy (1 variants)
- Arrhythmogenic_cardiomyopathy (1 variants)
- Ventricular_fibrillation (1 variants)
- Duchenne_muscular_dystrophy (1 variants)
- Arrhythmogenic_right_ventricular_dysplasia_1 (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. These statistics are base on transcript: NM_001005242.3. Only rare variants are included in the table.
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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 10 | 361 | 10 | 386 | ||
missense | 13 | 855 | 74 | 959 | ||
nonsense | 65 | 19 | 84 | |||
start loss | 1 | 3 | 1 | 5 | ||
frameshift | 108 | 78 | 190 | |||
splice donor/acceptor (+/-2bp) | 18 | 35 | 55 | |||
Total | 201 | 152 | 871 | 436 | 19 |
Highest pathogenic variant AF is 0.000076840515
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
PKP2 | protein_coding | protein_coding | ENST00000070846 | 14 | 106096 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
3.11e-18 | 0.117 | 125638 | 0 | 110 | 125748 | 0.000437 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -0.213 | 513 | 500 | 1.03 | 0.0000303 | 5724 |
Missense in Polyphen | 130 | 135.54 | 0.95909 | 1684 | ||
Synonymous | 0.216 | 208 | 212 | 0.981 | 0.0000142 | 1778 |
Loss of Function | 1.25 | 32 | 40.6 | 0.788 | 0.00000233 | 439 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00282 | 0.00266 |
Ashkenazi Jewish | 0.000298 | 0.000298 |
East Asian | 0.000326 | 0.000326 |
Finnish | 0.0000928 | 0.0000924 |
European (Non-Finnish) | 0.000406 | 0.000360 |
Middle Eastern | 0.000326 | 0.000326 |
South Asian | 0.000359 | 0.000327 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
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