PKP1

plakophilin 1, the group of Armadillo repeat containing|Plakophilins

Basic information

Region (hg38): 1:201283451-201332993

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ectodermal dysplasia/skin fragility syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic	9326952; 10951270; 1615972; 19016709; 22309335

ClinVar

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

• not provided (1 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.

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			9	21	7	37
missense			76	11	5	92
nonsense	1	1				2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region			1	4	1	6
non coding			51	19	80	150
Total	1	2	137	51	92

Variants in PKP1

This is a list of pathogenic ClinVar variants found in the PKP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-201283468-G-T		Epidermolysis bullosa simplex due to plakophilin deficiency	Uncertain significance (Feb 02, 2018)
1-201283573-A-T		Epidermolysis bullosa simplex due to plakophilin deficiency	Benign (Nov 12, 2018)
1-201283587-C-G		Epidermolysis bullosa simplex due to plakophilin deficiency	Likely benign (Jan 13, 2018)
1-201283607-G-A		Epidermolysis bullosa simplex due to plakophilin deficiency	Uncertain significance (Jan 13, 2018)
1-201283617-C-A		Epidermolysis bullosa simplex due to plakophilin deficiency	Benign (Jan 13, 2018)
1-201283717-G-T		Epidermolysis bullosa simplex due to plakophilin deficiency	Uncertain significance (Jan 13, 2018)
1-201283738-C-T		not specified • Epidermolysis bullosa simplex due to plakophilin deficiency	Benign (Jan 29, 2024)
1-201283829-G-A		Inborn genetic diseases	Uncertain significance (Mar 04, 2024)
1-201283838-A-T		Epidermolysis bullosa simplex due to plakophilin deficiency • Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
1-201283853-C-T		Inborn genetic diseases	Uncertain significance (Aug 14, 2023)
1-201283856-C-A		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
1-201283901-C-A			Likely benign (Apr 09, 2023)
1-201283911-G-C		PKP1-related disorder	Likely benign (May 22, 2023)
1-201283914-C-T			Likely benign (Oct 19, 2022)
1-201283991-C-G			Benign (May 15, 2021)
1-201284153-A-G			Benign (Nov 12, 2018)
1-201293627-G-T			Benign (Jun 19, 2021)
1-201293798-C-T			Benign (May 22, 2021)
1-201293941-G-C		Epidermolysis bullosa simplex due to plakophilin deficiency	Likely pathogenic (-)
1-201293944-T-A		Inborn genetic diseases	Uncertain significance (Sep 21, 2023)
1-201293945-C-A		Inborn genetic diseases	Uncertain significance (Sep 21, 2023)
1-201293980-G-A		Epidermolysis bullosa simplex due to plakophilin deficiency	Conflicting classifications of pathogenicity (Dec 15, 2022)
1-201293981-G-A			Uncertain significance (-)
1-201294002-A-G		Epidermolysis bullosa simplex due to plakophilin deficiency	Conflicting classifications of pathogenicity (Jan 26, 2023)
1-201294011-A-G		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PKP1	protein_coding	protein_coding	ENST00000263946	14	49542

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000583	0.999	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.320	453	434	1.04	0.0000281	4877
Missense in Polyphen		123	140.57	0.87499		1525
Synonymous	-1.39	208	184	1.13	0.0000125	1437
Loss of Function	3.56	12	34.6	0.347	0.00000173	398

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000268	0.000268
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000441	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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