PKP1

Chr 1q32.1

plakophilin 1

Aliases:: B6P
MANE:: ENST00000367324.8

OMIM: 601975 ↗NCBI: 5317 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

PKP1 · Q13835

v62025-08-01

Predicted Aligned Error matrix for PKP1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

69.0/ 100

Low

747 residues

Confidence breakdown

Very high(≥ 90)41%
Confident(70–90)17%
Low(50–70)7%
Very low(< 50)36%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Ectodermal dysplasia
BIALLELIC, autosomal or pseudoautosomal
Ectodermal dysplasia without a known gene mutation
BIALLELIC, autosomal or pseudoautosomal
Epidermolysis bullosa
BIALLELIC, autosomal or pseudoautosomal
Epidermolysis bullosa and congenital skin fragility
BIALLELIC, autosomal or pseudoautosomal
Palmoplantar keratodermas
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

epidermolysis bullosa simplex due to plakophilin deficiency
0.77
seborrheic keratosis
0.40
skin aging
0.34
skin disorder
0.31
knee fracture
0.28
congenital anomaly of cardiovascular system
0.28
hereditary disease
0.19
esophageal squamous cell carcinoma
0.09
ovarian carcinoma
0.07
ovarian cancer
0.07

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Plakophilin-1

A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:23444369). Plays a role in desmosome protein expression regulation and localization to the desmosomal plaque, thereby maintaining cell sheet integrity and anchorage of desmosomes to intermediate filaments (PubMed:10852826, PubMed:23444369). Required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, YAP1, PKP1 and YWHAG (PubMed:31835537). Positively regulates differentiation of keratinocytes, potentially via promoting localization of DSG1 at desmosome cell junctions (By similarity). Required for calcium-independent development and maturation of desmosome plaques specifically at lateral cell-cell contacts in differentiating keratinocytes (By similarity). Plays a role in the maintenance of DSG3 protein abundance, DSG3 clustering and localization of these clusters to the cell membrane in keratinocytes (By similarity). May also promote keratinocyte proliferation and morphogenesis during postnatal development (PubMed:9326952). Required for tight junction inside-out transepidermal barrier function of the skin (By similarity). Promotes Wnt-mediated proliferation and differentiation of ameloblasts, via facilitating TJP1/ZO-1 localization to tight junctions (By similarity). Binds single-stranded DNA (ssDNA), and may thereby play a role in sensing DNA damage and promoting cell survival (PubMed:20613778). Positively regulates cap-dependent translation and as a result cell proliferation, via recruitment of EIF4A1 to the initiation complex and promotion of EIF4A1 ATPase activity (PubMed:20156963, PubMed:23444369). Regulates the mRNA stability and protein abundance of desmosome components PKP2, PKP3, DSC2 and DSP, potentially via its interaction with FXR1 (PubMed:25225333)