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; AllianceGenome:HGNC:9024
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 may regulate the signaling activity of beta-catenin and is required to maintain transcription of genes that control intracellular calcium cycling including ryanodine receptor 2, ankyrin-B, triadin, and calcium channel, voltage-dependent, L type, alpha 1C. Mutations in this gene are associated with different inherited cardiac conditions including Arrythmogenic Cardiomyopathy, Brugada Syndrome, and Idiopathic Ventricular Fibrillation. A processed pseudogene with high similarity to this gene has been mapped to chromosome 12p13. [provided by RefSeq, May 2022]
Expression: Biased expression in heart (RPKM 72.8), colon (RPKM 29.6) and 12 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12p11.21

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (32790755..32896777, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (32667065..32772770, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (32943689..33049711, 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 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 Functions

What's a GeneRIF?

Biallelic PKP2 loss of function variants are associated with a lethal perinatal-onset biventricular dilated cardiomyopathy with excessive trabeculations and ventricular septal defects.
Title: Biallelic PKP2 loss of function variants are associated with a lethal perinatal-onset biventricular dilated cardiomyopathy with excessive trabeculations and ventricular septal defects.
Downregulated expression of plakophilin-2 gene in patients with colon adenocarcinoma predicts an unfavorable prognosis and immune infiltrate.
Title: Downregulated expression of plakophilin-2 gene in patients with colon adenocarcinoma predicts an unfavorable prognosis and immune infiltrate.
Plakophilin 2 regulates intestinal barrier function by modulating protein kinase C activity in vitro.
Title: Plakophilin 2 regulates intestinal barrier function by modulating protein kinase C activity in vitro.
Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence.
Title: Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence.
The Novel Variant NP_00454563.2 (p.Glu259Glyfs*77) in Gene PKP2 Associated with Arrhythmogenic Cardiomyopathy in 8 Families from Malaga, Spain.
Title: The Novel Variant NP_00454563.2 (p.Glu259Glyfs*77) in Gene PKP2 Associated with Arrhythmogenic Cardiomyopathy in 8 Families from Malaga, Spain.
Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC.
Title: Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC.
Population Prevalence of Premature Truncating Variants in Plakophilin-2 and Association With Arrhythmogenic Right Ventricular Cardiomyopathy: A UK Biobank Analysis.
Title: Population Prevalence of Premature Truncating Variants in Plakophilin-2 and Association With Arrhythmogenic Right Ventricular Cardiomyopathy: A UK Biobank Analysis.
Decreased Expression of Plakophilin-2 and alphaT-Catenin in Arrhythmogenic Right Ventricular Cardiomyopathy: Potential Markers for Diagnosis.
Title: Decreased Expression of Plakophilin-2 and αT-Catenin in Arrhythmogenic Right Ventricular Cardiomyopathy: Potential Markers for Diagnosis.
Modeling reduced contractility and impaired desmosome assembly due to plakophilin-2 deficiency using isogenic iPS cell-derived cardiomyocytes.
Title: Modeling reduced contractility and impaired desmosome assembly due to plakophilin-2 deficiency using isogenic iPS cell-derived cardiomyocytes.
Long non-coding RNA HCG11 enhances osteosarcoma phenotypes by sponging miR-1245b-5p that directly inhibits plakophilin 2.
Title: Long non-coding RNA HCG11 enhances osteosarcoma phenotypes by sponging miR-1245b-5p that directly inhibits plakophilin 2.

Submit: New GeneRIF Correction See all GeneRIFs (87)

Phenotypes

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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 MedGen: C0349788 GeneReviews: Arrhythmogenic Right Ventricular Cardiomyopathy Overview	Compare labs
Arrhythmogenic right ventricular dysplasia 9 MedGen: C1836906 OMIM: 609040 GeneReviews: Arrhythmogenic Right Ventricular Cardiomyopathy Overview	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2023-05-10) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2023-05-10) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS 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)

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

Gene Ontology Provided by GOA

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

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

Component	Evidence Code	Pubs
is_active_in adherens junction	IBA Inferred from Biological aspect of Ancestor more info
located_in cell junction	IDA Inferred from Direct Assay more info
located_in cell tip	IEA Inferred from Electronic Annotation more info
located_in cell-cell junction	IDA Inferred from Direct Assay more info	PubMed
located_in cell-cell junction	ISS Inferred from Sequence or Structural Similarity more info
located_in cornified envelope	TAS Traceable Author Statement more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in desmosome	IDA Inferred from Direct Assay more info	PubMed
located_in desmosome	ISS Inferred from Sequence or Structural Similarity more info
located_in desmosome	NAS Non-traceable Author Statement more info	PubMed
is_active_in intercalated disc	IBA Inferred from Biological aspect of Ancestor more info
located_in intercalated disc	IDA Inferred from Direct Assay more info	PubMed
located_in intercalated disc	ISS Inferred from Sequence or Structural Similarity more info
located_in intermediate filament	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in 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_001005242.3 → NP_001005242.2 plakophilin-2 isoform 2a

See identical proteins and their annotated locations for NP_001005242.2

Status: REVIEWED

Source sequence(s)

AC087588, AW439621, BC126199, DB454360

Consensus CDS

CCDS31771.1

UniProtKB/TrEMBL

B8QGS9

Related

ENSP00000342800.5, ENST00000340811.9

Conserved Domains (2) summary

smart00185
Location:426 → 467

ARM; Armadillo/beta-catenin-like repeats

sd00043
Location:430 → 467

ARM; armadillo repeat [structural motif]
NM_001407155.1 → NP_001394084.1 plakophilin-2 isoform 3

Status: REVIEWED

Source sequence(s)

AC087311, AC087588

UniProtKB/TrEMBL

A0A8V8TPU9

Related

ENSP00000515065.2, ENST00000700559.2
NM_001407156.1 → NP_001394085.1 plakophilin-2 isoform 4

Status: REVIEWED

Source sequence(s)

AC087311, AC087588
NM_001407157.1 → NP_001394086.1 plakophilin-2 isoform 5

Status: REVIEWED

Source sequence(s)

AC087311, AC087588
NM_001407158.1 → NP_001394087.1 plakophilin-2 isoform 6

Status: REVIEWED

Source sequence(s)

AC087311, AC087588
NM_001407159.1 → NP_001394088.1 plakophilin-2 isoform 6

Status: REVIEWED

Source sequence(s)

AC087311, AC087588
NM_001407160.1 → NP_001394089.1 plakophilin-2 isoform 7

Status: REVIEWED

Source sequence(s)

AC087311, AC087588
NM_001407161.1 → NP_001394090.1 plakophilin-2 isoform 8

Status: REVIEWED

Source sequence(s)

AC087311, AC087588

UniProtKB/TrEMBL

A0AAQ5BGY2

Related

ENSP00000519095.1, ENST00000700564.2
NM_001407162.1 → NP_001394091.1 plakophilin-2 isoform 9

Status: REVIEWED

Source sequence(s)

AC087311, AC087588
NM_004572.4 → NP_004563.2 plakophilin-2 isoform 2b

See identical proteins and their annotated locations for NP_004563.2

Status: REVIEWED

Source sequence(s)

AC087588, AU125826, AW439621, DB454360, X97675

Consensus CDS

CCDS8731.1

UniProtKB/Swiss-Prot

A0AV37, B8QFA1, B8QGS6, B8QGS7, D3DUW9, Q4VC01, Q99959, Q99960

UniProtKB/TrEMBL

B8QGS9

Related

ENSP00000070846.6, ENST00000070846.11

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]