PKP4

protein-coding

plakophilin 4, the group of p120 catenin family|Armadillo repeat containing

Gene summary

Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

MANE transcript

NM_003628.6

Inheritance

—

ClinVar variants

U:454B:263

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr2:158,456,952-158,682,879

External References & Databases

Ensembl (ENSG00000144283)

Transcript & Mutation Effects

hg38 • Region Span ~225.9 kb

Loading mutation effect viewer...

GenCC 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 PKP4 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 700

not providedTotal: 10

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Autism spectrum disorderTotal: 1

Syndromic intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003628.6. 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			3 clinvar	247 clinvar		250
missense			444 clinvar	15 clinvar		459
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar		1 clinvar	8
Total	0	0	454	262	1	717

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 66 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003628.6	RefSeq	NP_003619.2	21	MANE Select
ENST00000389759.8	Ensembl	ENSP00000374409.3	21	MANE Select
NM_001005476.4	RefSeq	NP_001005476.1	20	Standard
NM_001304969.3	RefSeq	NP_001291898.1	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Keratinization
Developmental Biology
TCR
Fibroblast growth factor-1
EGFR1

Biological Process

cell-cell junction assembly
cell-cell signaling
regulation of cell adhesion
keratinization
positive regulation of cytokinesis

Molecular Function

protein binding
cadherin binding

Cellular Component

spindle pole
cornified envelope
nucleus
cytoplasm
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389759
Coding exons: 21
Length: 225916
Individuals with no LoFs: 124318
Homozygous LoFs: 34
Heterozygous LoFs: 1396
Defined: 125748
p: 0.00570

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.973	613	685	0.895	0.0000391	7633
Missense (PolyPhen)		167	217.26	0.76865		2581
Synonymous	0.382	267	275	0.971	0.0000164	2459
Loss of Function	3.97	32	67.1	0.477	0.00000401	719

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00080	0.00080	rare
Latino/Admixed American	0.040	0.039	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00075	0.00072	rare
Other	0.0041	0.0041	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques. {ECO:0000269|PubMed:17115030}.;

Recessive Scores

pRec: 0.127

Intolerance Scores

LoFtool: 0.319
RVIS EVS: -1.08
RVIS percentile EVS: 7.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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