PPL
protein-codingperiplakin, the group of Plakins
Gene summary
The protein encoded by this gene is a component of desmosomes and of the epidermal cornified envelope in keratinocytes. The N-terminal domain of this protein interacts with the plasma membrane and its C-terminus interacts with intermediate filaments. Through its rod domain, this protein forms complexes with envoplakin. This protein may serve as a link between the cornified envelope and desmosomes as well as intermediate filaments. AKT1/PKB, a protein kinase mediating a variety of cell growth and survival signaling processes, is reported to interact with this protein, suggesting a possible role for this protein as a localization signal in AKT1-mediated signaling. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~78.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002705.5. 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 | 5 | 13 | 11 | 29 | ||
| missense | 419 | 28 | 10 | 457 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 13 | 13 | ||||
| Total | 0 | 0 | 439 | 41 | 21 | 501 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002696.4 | 22 | MANE Select | |
| Ensembl | ENSP00000340510.2 | 22 | MANE Select | |
| Ensembl | ENSP00000465640.1 | 22 | Standard | |
| Ensembl | ENSP00000465640.1 | 22 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
- Keratinization
- Developmental Biology
- Butyrophilin (BTN) family interactions
- Immune System
Biological Process
- response to mechanical stimulus
- wound healing
- intermediate filament cytoskeleton organization
- cornification
Molecular Function
- structural molecule activity
- structural constituent of cytoskeleton
- protein binding
- cadherin binding
Cellular Component
- cornified envelope
- nucleus
- cytoplasm
- mitochondrion
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000345988
- Coding exons
- 22
- Length
- 78235
- Individuals with no LoFs
- 125495
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 252
- Defined
- 125748
- p
- 0.00101
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -3.66 | 1408 | 1.07e+3 | 1.31 | 0.0000744 | 11425 |
| Missense (PolyPhen) | 414 | 305.05 | 1.3572 | 3382 | ||
| Synonymous | -4.86 | 603 | 469 | 1.29 | 0.0000322 | 3418 |
| Loss of Function | 1.33 | 72 | 85.2 | 0.845 | 0.00000443 | 948 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00081 | 0.00080 | rare |
| Latino/Admixed American | 0.0012 | 0.0012 | notable |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.0012 | 0.0012 | notable |
| Finnish | 0.00098 | 0.00092 | rare |
| European (Non-Finnish) | 0.00080 | 0.00078 | rare |
| South Asian | 0.0019 | 0.0019 | notable |
| Other | 0.0011 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments. May act as a localization signal in PKB/AKT-mediated signaling. {ECO:0000269|PubMed:9412476}.;
Recessive Scores
- pRec
- 0.300
Intolerance Scores
- LoFtool
- 0.597
- RVIS EVS
- -0.35
- RVIS percentile EVS
- 29.55
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.894
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |