PKP4: Plakophilin 4 Gene
A comprehensive resource for PKP4 gene information, including expression, mutations, and associated diseases.
Gene Information Card
| Symbol | PKP4 |
|---|---|
| Full Name | Plakophilin 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q24.1 |
| NCBI Gene ID | 8502 ncbi.nlm.nih.gov/gene/8502 |
| Ensembl ID | ENSG00000144224 |
| UniProt ID | Q99569 |
| OMIM ID | 604276 |
| HGNC ID | 9025 |
| Aliases | p0071, plakophilin-4, armadillo repeat protein deleted in velo-cardio-facial syndrome |
Description
PKP4 (plakophilin 4) is a protein-coding gene that encodes a member of the armadillo repeat protein family. The protein localizes to desmosomes and adherens junctions, playing a critical role in cell-cell adhesion and signaling. It is involved in the structural integrity of tissues and has been implicated in cancer progression and cardiac diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Arrhythmogenic right ventricular cardiomyopathy (ARVC) | Disruption of desmosomal integrity due to PKP4 mutations leads to impaired cell adhesion and cardiac dysfunction. | ClinVar, OMIM |
| Colorectal cancer | Overexpression of PKP4 promotes tumor cell migration and invasion via Wnt/β-catenin signaling. | COSMIC, PubMed |
| Breast cancer | Altered PKP4 expression correlates with poor prognosis and metastatic potential. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 15.2 | Medium |
| Liver | 8.5 | Low |
| Lung | 12.1 | Medium |
| Kidney | 10.3 | Medium |
| Brain | 6.7 | Low |
| Colon | 18.9 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.5 | Cervical cancer cell line |
| MCF7 | 11.2 | Breast cancer cell line |
| A549 | 9.8 | Lung cancer cell line |
| HCT116 | 20.1 | Colorectal cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | 0.02% | Alters protein stability and desmosome assembly |
| c.567delG (p.Glu189fs) | Frameshift | 0.01% | Loss of function, associated with ARVC |
| c.890A>G (p.Asn297Ser) | Missense | 0.03% | Gain of function, increased cell migration in cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein, leading to reduced desmosomal adhesion and increased risk of cardiomyopathy.
Gain of Function (GOF)
Missense mutations that enhance PKP4 interaction with β-catenin, promoting Wnt signaling and tumor progression.
Dominant Negative (DN)
Mutations that produce a truncated protein interfering with wild-type PKP4 function, observed in some ARVC cases.
View complete mutation data：
Gene Ontology (GO)
| • cell-cell adherens junction (GO:0005913) | • cell adhesion (GO:0007155) |
| • plasma membrane (GO:0005886) | • structural molecule activity (GO:0005198) |
| • homophilic cell adhesion via plasma membrane adhesion molecules (GO:0007156) |
Pathways
• Desmosome assembly (Reactome: R-HSA-4467285)
• Cell junction organization (Reactome: R-HSA-446353)
• Wnt signaling pathway (KEGG: hsa04310)
Protein Summary
Plakophilin 4 (PKP4) is a 125 kDa armadillo repeat protein that localizes to desmosomes and adherens junctions. It contains 10 armadillo repeats and an N-terminal head domain. PKP4 interacts with desmoplakin, plakoglobin, and β-catenin, stabilizing cell-cell contacts. It also shuttles to the nucleus to modulate gene expression. Post-translational modifications include phosphorylation, which regulates its localization and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PKP4 Knockout HEK293 Cell Line | EDJ-KQ6259 | Human | 8502 | Details Get a Quote |
| PKP4 Knockout A-549 Cell Line | EDJ-KQ30136 | Human | 8502 | Details Get a Quote |
| PKP4 Knockout HCT 116 Cell Line | EDJ-KQ30137 | Human | 8502 | Details Get a Quote |
| PKP4 Knockout HeLa Cell Line | EDJ-KQ30138 | Human | 8502 | Details Get a Quote |
