PKP3

protein-coding

plakophilin 3, 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 act in cellular desmosome-dependent adhesion and signaling pathways. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

MANE transcript

NM_007183.4

Inheritance

—

ClinVar variants

U:200B:15

Top phenotype

Decreased total neutrophil count

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr11:392,614-404,908

External References & Databases

Ensembl (ENSG00000184363)

Transcript & Mutation Effects

hg38 • Region Span ~12.3 kb

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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 PKP3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 199

not providedTotal: 12

Decreased total neutrophil countTotal: 1

Decreased total lymphocyte countTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007183.4. 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	5 clinvar	1 clinvar	9
missense			196 clinvar	6 clinvar	3 clinvar	205
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	200	11	4	215

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007183.4	RefSeq	NP_009114.1	13	MANE Select
ENST00000331563.7	Ensembl	ENSP00000331678.2	13	MANE Select
NM_001303029.2	RefSeq	NP_001289958.1	14	Standard
ENST00000525642.1	Ensembl	ENSP00000436847.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Keratinization
Developmental Biology
EGFR1
Formation of the cornified envelope

Biological Process

desmosome assembly
regulation of translation
cell-cell junction assembly
positive regulation of gene expression
keratinization

Molecular Function

RNA binding
protein binding
enzyme binding
translation regulator activity
alpha-catenin binding

Cellular Component

cornified envelope
nucleus
nucleoplasm
cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000331563
Coding exons: 13
Length: 12295
Individuals with no LoFs: 125103
Homozygous LoFs: 1
Heterozygous LoFs: 28
Defined: 125132
p: 0.000116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.734	523	478	1.09	0.0000339	4982
Missense (PolyPhen)		203	192.96	1.052		1897
Synonymous	-1.98	258	221	1.17	0.0000162	1736
Loss of Function	2.88	12	28.6	0.420	0.00000162	323

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00011	0.00010	rare
East Asian	0.00012	0.00011	rare
Finnish	0.00026	0.00018	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.00014	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in junctional plaques.;

Recessive Scores

pRec: 0.114

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.407

Gene Damage Prediction

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