PKP2 Gene (Protein Coding)

Plakophilin 2

GC12M032790
GIFtS:
46
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 enco... See more...

Aliases for PKP2 Gene

Aliases for PKP2 Gene

  • Plakophilin 2 2 3 5
  • Plakophilin-2 3 4
  • ARVD9 3
  • PKP2 5

External Ids for PKP2 Gene

Previous GeneCards Identifiers for PKP2 Gene

  • GC12M033434
  • GC12M033020
  • GC12M032844
  • GC12M032835
  • GC12M032834
  • GC12M032943
  • GC12M032696

Summaries for PKP2 Gene

Entrez Gene Summary for PKP2 Gene

  • 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]

GeneCards Summary for PKP2 Gene

PKP2 (Plakophilin 2) is a Protein Coding gene. Diseases associated with PKP2 include Arrhythmogenic Right Ventricular Dysplasia, Familial, 9 and Arrhythmogenic Right Ventricular Cardiomyopathy. Among its related pathways are Arrhythmogenic right ventricular cardiomyopathy and Cytoskeleton remodeling Neurofilaments. Gene Ontology (GO) annotations related to this gene include binding and protein kinase C binding. An important paralog of this gene is CTNND2.

UniProtKB/Swiss-Prot Summary for PKP2 Gene

Gene Wiki entry for PKP2 Gene

Additional gene information for PKP2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PKP2 Gene

Genomics for PKP2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for PKP2 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH12J032891 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 260.7 +1.3 1308 8.7 ZSCAN16 ZBTB10 FEZF1 CEBPA ZNF217 CTCF ZEB1 ELF1 ZIC2 HOMEZ PKP2 ENSG00000257435 lnc-YARS2-3 ENSG00000257511 HSALNG0090304 lnc-DNM1L-5 RF00017-1128 YARS2
GH12J032873 Enhancer 0.7 Ensembl ENCODE dbSUPER 17.3 +21.4 21383 2.8 CEBPB CEBPG PKP2 RF00017-1128 lnc-DNM1L-5 lnc-YARS2-3 YARS2
GH12J032843 Enhancer 0.7 Ensembl ENCODE dbSUPER 11.5 +52.9 52876 1.4 CEBPB PRDM6 PKP2 RF00017-1128 ENSG00000274976 YARS2
GH12J032916 Enhancer 1.1 FANTOM5 Ensembl ENCODE 6.2 -22.7 -22735 5.6 ARID3A FEZF1 ZNF217 CTCF CEBPB REST CUX1 EP300 SMC3 RAD21 piR-57133-105 PKP2 ENSG00000257435 HSALNG0090304 RF00017-1128 SYT10
GH12J032856 Enhancer 0.4 Ensembl dbSUPER 12.3 +39.7 39676 0.2 ZNF121 PKP2 RF00017-1128 ENSG00000274976 YARS2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PKP2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PKP2

Genomic Locations for PKP2 Gene

Latest Assembly
chr12:32,790,755-32,896,777
(GRCh38/hg38)
Size:
106,023 bases
Orientation:
Minus strand

Previous Assembly
chr12:32,943,689-33,049,711
(GRCh37/hg19 by Entrez Gene)
Size:
106,023 bases
Orientation:
Minus strand

chr12:32,943,679-33,049,774
(GRCh37/hg19 by Ensembl)
Size:
106,096 bases
Orientation:
Minus strand

Genomic View for PKP2 Gene

Genes around PKP2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PKP2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PKP2 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for PKP2 Gene

Proteins for PKP2 Gene

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  • Protein details for PKP2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99959-PKP2_HUMAN
    Recommended name:
    Plakophilin-2
    Protein Accession:
    Q99959
    Secondary Accessions:
    • A0AV37
    • B8QFA1
    • B8QGS6
    • B8QGS7
    • D3DUW9
    • Q4VC01
    • Q99960

    Protein attributes for PKP2 Gene

    Size:
    881 amino acids
    Molecular mass:
    97415 Da
    Quaternary structure:
    • Interacts with DSC2. Interacts with JUP and desmoplakin/DSP.
    Miscellaneous:
    • [Isoform 2]: Undetected in heart.
    • [Isoform 1]: Major isoform in heart.

    Three dimensional structures from OCA and Proteopedia for PKP2 Gene

    Alternative splice isoforms for PKP2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PKP2 Gene

Protein Expression for PKP2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for PKP2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PKP2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for PKP2 Gene

Domains & Families for PKP2 Gene

Gene Families for PKP2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for PKP2 Gene

InterPro:
Blocks:
  • Armadillo repeat
ProtoNet:

Suggested Antigen Peptide Sequences for PKP2 Gene

GenScript: Design optimal peptide antigens:
  • Plakophilin 2, isoform CRA_d (A0AV37_HUMAN)
  • Plakophilin-2 transcript variant 2b (B8QFA1_HUMAN)
  • Plakophilin-2 (B8QGS6_HUMAN)
  • Plakophilin-2 (B8QGS7_HUMAN)
  • Truncated plakophilin-2 (B8QGS8_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q99959

UniProtKB/Swiss-Prot:

PKP2_HUMAN :
  • Belongs to the beta-catenin family.
Family:
  • Belongs to the beta-catenin family.
genes like me logo Genes that share domains with PKP2: view

Function for PKP2 Gene

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Molecular function for PKP2 Gene

UniProtKB/Swiss-Prot Function:
May play a role in junctional plaques.
GENATLAS Biochemistry:
plakophilin 2,component of karyoplasm and desmosomal plaque protein of desmosomes in stratified epithelia,also expressed in the nucleus of non epithelial cells, homologous to Drosophila Armadillo segment polarity gene

Phenotypes From GWAS Catalog for PKP2 Gene

Gene Ontology (GO) - Molecular Function for PKP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005080 protein kinase C binding IPI 18474624
GO:0005515 protein binding IPI 10852826
GO:0017080 sodium channel regulator activity ISS --
GO:0019215 intermediate filament binding IDA 10852826
GO:0044325 ion channel binding ISS --
genes like me logo Genes that share ontologies with PKP2: view
genes like me logo Genes that share phenotypes with PKP2: view

Human Phenotype Ontology for PKP2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for PKP2 Gene

MGI Knock Outs for PKP2:

Animal Models for research

miRNA for PKP2 Gene

miRTarBase miRNAs that target PKP2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PKP2

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for PKP2 Gene

Localization for PKP2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PKP2 Gene

Nucleus. Cell junction, desmosome. Note=Nuclear and associated with desmosomes.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PKP2 gene
Compartment Confidence
plasma membrane 5
nucleus 5
cytoskeleton 4
cytosol 3
extracellular 2
endoplasmic reticulum 2
mitochondrion 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (4)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PKP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001533 cornified envelope TAS --
GO:0005634 nucleus IBA,NAS 8922383
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IBA 21873635
GO:0005882 intermediate filament ISS --
genes like me logo Genes that share ontologies with PKP2: view

Pathways & Interactions for PKP2 Gene

genes like me logo Genes that share pathways with PKP2: view

Pathways by source for PKP2 Gene

1 BioSystems pathway for PKP2 Gene
1 GeneGo (Thomson Reuters) pathway for PKP2 Gene
  • Cytoskeleton remodeling Keratin filaments

SIGNOR curated interactions for PKP2 Gene

Activates:

Gene Ontology (GO) - Biological Process for PKP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002159 desmosome assembly IMP 18474624
GO:0002934 desmosome organization IBA 21873635
GO:0007043 cell-cell junction assembly IBA 21873635
GO:0007155 cell adhesion IEA --
GO:0007507 heart development ISS --
genes like me logo Genes that share ontologies with PKP2: view

Drugs & Compounds for PKP2 Gene

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No Compound Related Data Available

Transcripts for PKP2 Gene

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mRNA/cDNA for PKP2 Gene

2 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PKP2

Alternative Splicing Database (ASD) splice patterns (SP) for PKP2 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b · 11c ^ 12a · 12b ^ 13 ^ 14a · 14b ^ 15a · 15b
SP1: - - - -
SP2: - - - - -
SP3: -
SP4:
SP5:
SP6: -

Relevant External Links for PKP2 Gene

GeneLoc Exon Structure for
PKP2

Expression for PKP2 Gene

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  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PKP2 Gene

mRNA expression in normal human tissues for PKP2 Gene
mRNA expression by GTEx for PKP2 GenemRNA expression by BioGPS for PKP2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PKP2 Gene

This gene is overexpressed in Heart - Left Ventricle (x19.8) and Heart - Atrial Appendage (x7.9).

Protein differential expression in normal tissues from HIPED for PKP2 Gene

This gene is overexpressed in Heart (35.9), Fetal heart (11.0), and Salivary gland (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PKP2 Gene



Protein tissue co-expression partners for PKP2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PKP2

SOURCE GeneReport for Unigene cluster for PKP2 Gene:

Hs.164384

mRNA Expression by UniProt/SwissProt for PKP2 Gene:

Q99959-PKP2_HUMAN
Tissue specificity: Detected in heart right ventricle (at protein level). Widely expressed. Found at desmosomal plaques in simple and stratified epithelia and in non-epithelial tissues such as myocardium and lymph node follicles. In most stratified epithelia found in the desmosomes of the basal cell layer and seems to be absent from suprabasal strata.

Evidence on tissue expression from TISSUES for PKP2 Gene

  • Liver(4.5)
  • Nervous system(4.5)
  • Heart(3.9)
  • Intestine(3.6)
  • Muscle(3.4)
  • Stomach(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for PKP2 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • cardiovascular
  • nervous
Regions:
Head and neck:
  • brain
  • ear
  • head
Thorax:
  • heart
  • heart valve
General:
  • blood
  • blood vessel
  • red blood cell
genes like me logo Genes that share expression patterns with PKP2: view

Primer products for research

Orthologs for PKP2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for PKP2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia PKP2 30 31
  • 98.81 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia PKP2 30 31
  • 88.72 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia PKP2 30 31
  • 87.83 (n)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia -- 31
  • 84 (a)
 OneToMany
-- 31
  • 77 (a)
 OneToMany
Mouse
(Mus musculus)
 Mammalia Pkp2 30 17 31
  • 81.13 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Pkp2 30
  • 80.92 (n)
Oppossum
(Monodelphis domestica)
 Mammalia PKP2 31
  • 76 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves PKP2 30 31
  • 67.07 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia PKP2 31
  • 56 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia pkp2 30
  • 59.19 (n)
Zebrafish
(Danio rerio)
 Actinopterygii pkp2 30 31
  • 50.13 (n)
 OneToOne
Species where no ortholog for PKP2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for PKP2 Gene

ENSEMBL:
Gene Tree for PKP2 (if available)
TreeFam:
Gene Tree for PKP2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PKP2: view image

Paralogs for PKP2 Gene

Paralogs for PKP2 Gene

(5) SIMAP similar genes for PKP2 Gene using alignment to 3 proteins:

  • PKP2_HUMAN
  • B8QGS8_HUMAN
  • B8QGS9_HUMAN

Pseudogenes.org Pseudogenes for PKP2 Gene

genes like me logo Genes that share paralogs with PKP2: view

Variants for PKP2 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PKP2 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
138692 Conflicting Interpretations: Cardiomyopathy; Arrhythmogenic right ventricular dysplasia 9 32,843,228(-) G/A
NM_004572.3(PKP2):c.1464C>T (p.Gly488=) 		SYNONYMOUS_VARIANT,INTRON
188656 Likely Benign: Cardiomyopathy 32,878,076(-) G/A
NM_004572.3(PKP2):c.804C>T (p.Val268=) 		SYNONYMOUS
201975 Uncertain Significance: Cardiomyopathy 32,878,294(-) G/A
NM_004572.3(PKP2):c.586C>T (p.Arg196Cys) 		MISSENSE
201984 Likely Pathogenic: Arrhythmogenic right ventricular dysplasia 9 32,850,764(-) A/T
NM_004572.3(PKP2):c.1378+2T>A 		SPLICE_DONOR
464434 Uncertain Significance: Cardiomyopathy; Arrhythmogenic right ventricular dysplasia 9; not specified 32,877,909(-) GCCT/AGGC
NM_001005242.2(PKP2):c.968_971inv (p.Gln323_Ala324delinsArgLeu) 		MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for PKP2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for PKP2 Gene

Variant ID Type Subtype PubMed ID
dgv796n106 CNV deletion 24896259
esv1043456 CNV deletion 17803354
esv2485280 CNV deletion 19546169
esv2745751 CNV deletion 23290073
esv2745753 CNV deletion 23290073
esv3252829 CNV deletion 24192839
esv3549028 CNV deletion 23714750
esv3629089 CNV loss 21293372
esv4479 CNV loss 18987735
esv8190 CNV loss 19470904
nsv1070523 CNV deletion 25765185
nsv516937 CNV loss 19592680
nsv526287 CNV loss 19592680
nsv958653 CNV deletion 24416366
nsv976595 CNV duplication 23825009

Variation tolerance for PKP2 Gene

Residual Variation Intolerance Score: 81.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.19; 75.97% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PKP2 Gene

Human Gene Mutation Database (HGMD)
PKP2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PKP2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PKP2 Gene

Disorders for PKP2 Gene

MalaCards: The human disease database

(43) MalaCards diseases for PKP2 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search PKP2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

PKP2_HUMAN
  • Arrhythmogenic right ventricular dysplasia, familial, 9 (ARVD9) [MIM:609040]: A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. {ECO:0000269 PubMed:15489853, ECO:0000269 PubMed:19533476, ECO:0000269 PubMed:19863551, ECO:0000269 PubMed:19955750, ECO:0000269 PubMed:20031617, ECO:0000269 PubMed:22781308}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for PKP2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with PKP2: view

No data available for Genatlas for PKP2 Gene

Publications for PKP2 Gene

  1. Missense variants in plakophilin-2 in arrhythmogenic right ventricular cardiomyopathy patients--disease-causing or innocent bystanders? (PMID: 19955750) Christensen AH … Svendsen JH (Cardiology 2010) 3 4 23 41
  2. Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy. (PMID: 20031617) den Haan AD … Judge DP (Circulation. Cardiovascular genetics 2009) 3 4 23 41
  3. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. (PMID: 15489853) Gerull B … Thierfelder L (Nature genetics 2004) 3 4 23 74
  4. Plakophilins 2a and 2b: constitutive proteins of dual location in the karyoplasm and the desmosomal plaque. (PMID: 8922383) Mertens C … Franke WW (The Journal of cell biology 1996) 2 3 4 23
  5. Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia. (PMID: 19863551) Barahona-Dussault C … Brugada R (Clinical genetics 2010) 3 4 41

ExternalLinks

View latest publications for PKP2 gene in Mastermind

Products for PKP2 Gene

  • Addgene plasmids for PKP2

Sources for PKP2 Gene