GeneBe

PKP1

plakophilin 1, the group of Armadillo repeat containing|Plakophilins

Basic information

Region (hg38): 1:201283452-201332993

Links

ENSG00000081277 ∙ NCBI:5317 ∙ OMIM:601975 ∙ HGNC:9023 ∙ Uniprot:Q13835 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • epidermolysis bullosa simplex due to plakophilin deficiency (Strong), mode of inheritance: AR
  • epidermolysis bullosa simplex due to plakophilin deficiency (Strong), mode of inheritance: AR
  • epidermolysis bullosa simplex due to plakophilin deficiency (Strong), mode of inheritance: AR
  • epidermolysis bullosa simplex due to plakophilin deficiency (Supportive), mode of inheritance: AR
  • epidermolysis bullosa simplex due to plakophilin deficiency (Strong), mode of inheritance: AR
  • epidermolysis bullosa simplex due to plakophilin deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ectodermal dysplasia/skin fragility syndromeARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDermatologic9326952; 10951270; 1615972; 19016709; 22309335

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PKP1 gene.

  • Inborn_genetic_diseases (110 variants)
  • not_provided (96 variants)
  • Epidermolysis_bullosa_simplex_due_to_plakophilin_deficiency (62 variants)
  • PKP1-related_disorder (11 variants)
  • not_specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PKP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001005337.3. 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.

EffectPLPVUSLBBSum
synonymous
9
clinvar
31
clinvar
4
clinvar
 44
missense
136
clinvar
15
clinvar
4
clinvar
 155
nonsense
2
clinvar
1
clinvar
 3
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
3
clinvar
1
clinvar
 4
Total 7 2 145 46 8

Highest pathogenic variant AF is 0.00000657246

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PKP1protein_codingprotein_codingENST00000263946 1449542
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.0005830.9991257310171257480.0000676
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.3204534341.040.00002814877
Missense in Polyphen123140.570.874991525
Synonymous-1.392081841.130.00001251437
Loss of Function3.561234.60.3470.00000173398

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002680.000268
Ashkenazi Jewish0.0001030.0000992
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.00004410.0000439
Middle Eastern0.00005440.0000544
South Asian0.00006530.0000653
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Seems to play a role in junctional plaques. Contributes to epidermal morphogenesis. {ECO:0000269|PubMed:9326952}.;
Pathway
EMT transition in Colorectal Cancer;Keratinization;Developmental Biology;Neutrophil degranulation;Apoptotic cleavage of cell adhesion proteins;Apoptotic cleavage of cellular proteins;Innate Immune System;Immune System;Apoptotic execution phase;Apoptosis;Programmed Cell Death;Formation of the cornified envelope (Consensus)

Recessive Scores

pRec
0.165

Intolerance Scores

loftool
0.440
rvis_EVS
1.03
rvis_percentile_EVS
91.09

Haploinsufficiency Scores

pHI
0.883
hipred
Y
hipred_score
0.670
ghis
0.480

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.830

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Pkp1
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); cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;

Gene ontology

Biological process
cell-cell junction assembly;cell adhesion;signal transduction;positive regulation of gene expression;keratinization;neutrophil degranulation;intermediate filament bundle assembly;cornification;cell-cell adhesion;negative regulation of mRNA catabolic process
Cellular component
cornified envelope;nucleus;nucleoplasm;cytoplasm;intermediate filament;plasma membrane;cell-cell junction;cell-cell adherens junction;desmosome;intracellular membrane-bounded organelle;ficolin-1-rich granule membrane;messenger ribonucleoprotein complex
Molecular function
protein binding;lamin binding;intermediate filament binding;structural constituent of epidermis;cadherin binding