PKP2 plakophilin 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PKP2provided by HGNC
Official Full Name: plakophilin 2provided by HGNC
Primary source: HGNC:HGNC:9024
See related: Ensembl:ENSG00000057294 MIM:602861
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ARVD9
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 gene product may regulate the signaling activity of beta-catenin. Two alternately spliced transcripts encoding two protein isoforms have been identified. A processed pseudogene with high similarity to this locus has been mapped to chromosome 12p13. [provided by RefSeq, Jul 2008]
Expression: Biased expression in heart (RPKM 72.8), colon (RPKM 29.6) and 12 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 12p11.21

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	12	NC_000012.12 (32790746..32896846, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (32943680..33049780, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Comparative analyses of the influenza-host protein interactomes identified PKP2 as a natural inhibitor of influenza A viruses polymerase complex.
Title: Comparative influenza protein interactomes identify the role of plakophilin 2 in virus restriction.
Results identified common and rare variants within plakophilin 2 protein (PKP2) to be associated with left ventricular mass (LVM).
Title: Sequencing of Linkage Region on Chromosome 12p11 Identifies <i>PKP2</i> as a Candidate Gene for Left Ventricular Mass in Dominican Families.
Our study describes various clinical parameters in ACM patients and a recessive plakophilin 2 mutation after a limited PKP2 gene sequencing.
Title: Clinical profile in arrhythmogenic cardiomyopathy and a recessive plakophilin-2 gene mutation.
Authors show that the PKP2 gene encoding the desmosomal protein Plakophilin-2 is a novel direct transcriptional target of Wnt/beta-catenin in normal and colon cancer-associated fibroblasts.
Title: The human PKP2/plakophilin-2 gene is induced by Wnt/β-catenin in normal and colon cancer-associated fibroblasts.
Human iPSC line was generated from patient-specific adipose tissue-derived mesenchymal multipotent stromal cells carrying two mutations in plakophilin-2 (PKP2) gene using non-integrative reprogramming method.
Title: Generation of iPSC line from patient with arrhythmogenic right ventricular cardiomyopathy carrying mutations in PKP2 gene.
The rare incidence of PKP2 mutation in sudden unexplained noctural death syndrome (SUNDS, 1%) supports the previous viewpoint that SUNDS is most likely an allelic disorder as Brugada syndrome
Title: Molecular Autopsy of Desmosomal Protein Plakophilin-2 in Sudden Unexplained Nocturnal Death Syndrome.
Up-regulation of plakophilin-2 (PKP2) is correlated with the progression of glioma. Study uncovers a potential role for PKP2 in the pathogenic process of glioma, suggesting that PKP2 may be a promising therapeutic target of glioma.
Title: Up-regulation of plakophilin-2 is correlated with the progression of glioma.
Screening for CNVs in desmosome genes is useful to identify the genetic basis of disease in clinically suspected ARVC patients.
Title: Quantitative analysis of PKP2 and neighbouring genes in a patient with arrhythmogenic right ventricular cardiomyopathy caused by heterozygous PKP2 deletion.
a novel homozygous Plakophilin 2-gene mutation has a role in advanced cardiomyopathy
Title: High proportion of genetic cases in patients with advanced cardiomyopathy including a novel homozygous Plakophilin 2-gene mutation.
An intronic mutation of c.2577+1G>T in the PKP2 gene causes a nonsyndromic form of Arrhythmogenic Right Ventricular Cardiomyopathy without cutaneous Involvements.
Title: Autosomal Recessive Nonsyndromic Arrhythmogenic Right Ventricular Cardiomyopathy without Cutaneous Involvements: A Novel Mutation.

Submit: New GeneRIF Correction See all GeneRIFs (67)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Professional guidelines

Description
Professional guideline ACMG 2013 The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in PKP2 that are pathogenic or expected to be pathogenic. GuidelinePubMed

Associated conditions

Description	Tests
Arrhythmogenic right ventricular cardiomyopathy, type 9 MedGen: C1836906 OMIM: 609040 GeneReviews: Arrhythmogenic Right Ventricular Cardiomyopathy	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated (2015-12-17) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated (2015-12-17) ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Arrhythmogenic Right Ventricular Cardiomyopathy, organism-specific biosystem (from WikiPathways)
Arrhythmogenic Right Ventricular Cardiomyopathy, organism-specific biosystemAdapted from KEGG: http://www.genome.jp/kegg/pathway/hsa/hsa05412.html
Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystem (from KEGG)
Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystem (from KEGG)
Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
Formation of the cornified envelope, organism-specific biosystem (from REACTOME)
Formation of the cornified envelope, organism-specific biosystemAs keratinocytes progress towards the upper epidermis, they undergo a unique process of cell death termed cornification (Eckhart et al. 2013). This involves the crosslinking of keratinocyte proteins ...
Keratinization, organism-specific biosystem (from REACTOME)
Keratinization, organism-specific biosystemKeratins are the major structural protein of vertebrate epidermis, constituting up to 85% of a fully differentiated keratinocyte (Fuchs 1995). Keratins belong to a superfamily of intermediate filamen...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH46276 (e-PCR)
- UniSTS:72964

A004R21 (e-PCR)
- UniSTS:59208

SHGC-53044 (e-PCR)
- UniSTS:42318

G60319 (e-PCR)
- UniSTS:137575

RH80926 (e-PCR)
- UniSTS:83664

D12S1692 (e-PCR)
- UniSTS:40915

RH80560 (e-PCR)
- UniSTS:91350

RH65661 (e-PCR)
- UniSTS:41182

Homology

Homologs of the PKP2 gene: The PKP2 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 235 organisms have orthologs with human gene PKP2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
alpha-catenin binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
alpha-catenin binding	IPI Inferred from Physical Interaction more info	PubMed
cadherin binding	HDA more info	PubMed
cadherin binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication	IC Inferred by Curator more info	PubMed
intermediate filament binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
intermediate filament binding	IDA Inferred from Direct Assay more info	PubMed
ion channel binding	ISS Inferred from Sequence or Structural Similarity more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase C binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein kinase C binding	IPI Inferred from Physical Interaction more info	PubMed
protein-containing complex scaffold activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein-containing complex scaffold activity	IMP Inferred from Mutant Phenotype more info	PubMed
sodium channel regulator activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
adherens junction maintenance	IBA Inferred from Biological aspect of Ancestor more info	PubMed
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	IMP Inferred from Mutant Phenotype more info	PubMed
cardiac muscle cell action potential involved in contraction	IMP Inferred from Mutant Phenotype more info	PubMed
cell communication by electrical coupling involved in cardiac conduction	ISS Inferred from Sequence or Structural Similarity more info
cell-cell adhesion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell-cell adhesion	ISS Inferred from Sequence or Structural Similarity more info
cell-cell adhesion	NAS Non-traceable Author Statement more info	PubMed
cell-cell junction assembly	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell-cell signaling involved in cardiac conduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell-cell signaling involved in cardiac conduction	IMP Inferred from Mutant Phenotype more info	PubMed
cornification	TAS Traceable Author Statement more info
desmosome assembly	IMP Inferred from Mutant Phenotype more info	PubMed
heart development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
heart development	ISS Inferred from Sequence or Structural Similarity more info
intermediate filament bundle assembly	IBA Inferred from Biological aspect of Ancestor more info	PubMed
intermediate filament bundle assembly	IMP Inferred from Mutant Phenotype more info	PubMed
keratinization	TAS Traceable Author Statement more info
maintenance of animal organ identity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of sodium ion transport	ISS Inferred from Sequence or Structural Similarity more info
protein localization to plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of heart rate by cardiac conduction	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of ventricular cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed
ventricular cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed
ventricular cardiac muscle tissue morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
adherens junction	ISS Inferred from Sequence or Structural Similarity more info
cell junction	IDA Inferred from Direct Assay more info
cell-cell adherens junction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell-cell junction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell-cell junction	ISS Inferred from Sequence or Structural Similarity more info
cornified envelope	TAS Traceable Author Statement more info
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
desmosome	ISS Inferred from Sequence or Structural Similarity more info
desmosome	NAS Non-traceable Author Statement more info	PubMed
integral component of membrane	TAS Traceable Author Statement more info	PubMed
intercalated disc	IBA Inferred from Biological aspect of Ancestor more info	PubMed
intercalated disc	IDA Inferred from Direct Assay more info	PubMed
intercalated disc	ISS Inferred from Sequence or Structural Similarity more info
intermediate filament	IBA Inferred from Biological aspect of Ancestor more info	PubMed
intermediate filament	ISS Inferred from Sequence or Structural Similarity more info
NOT messenger ribonucleoprotein complex	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	NAS Non-traceable Author Statement more info	PubMed
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: plakophilin-2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009000.1 RefSeqGene

Range

5001..111101

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_398

mRNA and Protein(s)

NM_001005242.2 → NP_001005242.2 plakophilin-2 isoform 2a

See identical proteins and their annotated locations for NP_001005242.2

Status: REVIEWED

Description

Transcript Variant: This transcript variant (2a) lacks an alternate exon as compared to transcript variant 2b and encodes the shorter isoform (2a).

Source sequence(s)

AC087588, AW439621, BC126199, DB454360

Consensus CDS

CCDS31771.1

UniProtKB/Swiss-Prot

Q99959

Related

ENSP00000342800.4, ENST00000340811.8

Conserved Domains (2) summary

smart00185
Location:426 → 467

ARM; Armadillo/beta-catenin-like repeats

sd00043
Location:430 → 467

ARM; armadillo repeat [structural motif]
NM_004572.3 → NP_004563.2 plakophilin-2 isoform 2b

See identical proteins and their annotated locations for NP_004563.2

Status: REVIEWED

Description

Transcript Variant: This transcript variant (2b) represents the longer transcript variant and encodes the longer isoform.

Source sequence(s)

AC087588, AU125826, AW439621, DB454360, X97675

Consensus CDS

CCDS8731.1

UniProtKB/Swiss-Prot

Q99959

Related

ENSP00000070846.6, ENST00000070846.10

Conserved Domains (2) summary

cd00020
Location:675 → 804

ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...

sd00043
Location:388 → 424

ARM; armadillo repeat [structural motif]