PKP1
protein-codingplakophilin 1, the group of Armadillo repeat containing|Plakophilins
Gene summary
This gene encodes a member of the arm-repeat (armadillo) and plakophilin gene families. Plakophilin proteins contain numerous armadillo repeats, localize to cell desmosomes and nuclei, and participate in linking cadherins to intermediate filaments in the cytoskeleton. This protein may be involved in molecular recruitment and stabilization during desmosome formation. Mutations in this gene have been associated with the ectodermal dysplasia/skin fragility syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~49.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011472
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011472
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0011472
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0011472
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0011472
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0011472
Submitter: Genomics England PanelApp
Clinical Genomic Database (CGD)
Manifestation: Dermatologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PKP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001005337.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 10 | 38 | 2 | 50 | ||
| missense | 162 | 16 | 4 | 182 | ||
| nonsense | 2 | 1 | 1 | 4 | ||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 1 | 1 | 5 | ||
| Total | 7 | 2 | 174 | 54 | 6 | 243 |
Highest pathogenic variant AF is 0.000006572461
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001005337.1 | 13 | MANE Select | |
| Ensembl | ENSP00000356293.4 | 13 | MANE Select | |
| RefSeq | NP_000290.2 | 14 | Standard | |
| Ensembl | ENSP00000263946.3 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- EMT transition in Colorectal Cancer
- Keratinization
- Developmental Biology
- Neutrophil degranulation
- Apoptotic cleavage of cell adhesion proteins
Biological Process
- cell-cell junction assembly
- cell adhesion
- signal transduction
- positive regulation of gene expression
- keratinization
Molecular Function
- protein binding
- lamin binding
- intermediate filament binding
- structural constituent of epidermis
- cadherin binding
Cellular Component
- cornified envelope
- nucleus
- nucleoplasm
- cytoplasm
- intermediate filament
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000263946
- Coding exons
- 14
- Length
- 49542
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125748
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.320 | 453 | 434 | 1.04 | 0.0000281 | 4877 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Seems to play a role in junctional plaques. Contributes to epidermal morphogenesis. {ECO:0000269|PubMed:9326952}.;
Recessive Scores
- pRec
- 0.165
Intolerance Scores
- LoFtool
- 0.440
- RVIS EVS
- 1.03
- RVIS percentile EVS
- 91.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.830
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |