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    PKP2 plakophilin 2 [ Homo sapiens (human) ]

    Gene ID: 5318, updated on 7-Sep-2023

    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See PKP2 in Genome Data Viewer
    Location:
    12p11.21
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2023_03 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (32790755..32896777, complement)
    RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (32667065..32772770, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (32943689..33049711, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene nucleosome assembly protein 1 like 1 pseudogene Neighboring gene dynamin 1 like Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:32907771-32908410 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:32908411-32909050 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:32909051-32909690 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:32939152-32940351 Neighboring gene tyrosyl-tRNA synthetase 2 Neighboring gene NANOG hESC enhancer GRCh37_chr12:32986943-32987472 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:33031083-33031607 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:33043314-33043814 Neighboring gene ribosomal protein L35a pseudogene 27 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:33079663-33080862 Neighboring gene argininosuccinate synthetase 1 pseudogene 14 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr12:33333175-33334374 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:33591665-33592481 Neighboring gene synaptotagmin 10

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    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

    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

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC177501

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables alpha-catenin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables alpha-catenin binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables cadherin binding HDA PubMed 
    enables cadherin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables intermediate filament binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables molecular adaptor activity IBA
    Inferred from Biological aspect of Ancestor
    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 IBA
    Inferred from Biological aspect of Ancestor
    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
    PubMed 
    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 junction assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in cell-cell signaling involved in cardiac conduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in cell-cell signaling involved in cardiac conduction 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
    PubMed 
    involved_in heart development IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    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
    PubMed 
    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 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
    PubMed 
    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
    PubMed 
    located_in cell junction IDA
    Inferred from Direct Assay
    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
    PubMed 
    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
    PubMed 
    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
     
    is_active_in intermediate filament IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in intermediate filament ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    NOT part_of messenger ribonucleoprotein complex IDA
    Inferred from Direct Assay
    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
    PubMed 
    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
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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

    1. NG_009000.1 RefSeqGene

      Range
      5001..111101
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_398

    mRNA and Protein(s)

    1. NM_001005242.3NP_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/Swiss-Prot
      Q99959
      UniProtKB/TrEMBL
      B8QGS9
      Related
      ENSP00000342800.5, ENST00000340811.9
      Conserved Domains (2) summary
      smart00185
      Location:426467
      ARM; Armadillo/beta-catenin-like repeats
      sd00043
      Location:430467
      ARM; armadillo repeat [structural motif]
    2. NM_001407155.1NP_001394084.1  plakophilin-2 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC087311, AC087588
      UniProtKB/TrEMBL
      A0A8V8TQD7
      Related
      ENSP00000515065.2, ENST00000700559.2
    3. NM_001407156.1NP_001394085.1  plakophilin-2 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC087311, AC087588
      UniProtKB/TrEMBL
      B8QGS9
    4. NM_001407157.1NP_001394086.1  plakophilin-2 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC087311, AC087588
      UniProtKB/TrEMBL
      A0A8V8TQD7
    5. NM_001407158.1NP_001394087.1  plakophilin-2 isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC087311, AC087588
      UniProtKB/TrEMBL
      B8QGS9
    6. NM_001407159.1NP_001394088.1  plakophilin-2 isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC087311, AC087588
      UniProtKB/TrEMBL
      B8QGS9
    7. NM_001407160.1NP_001394089.1  plakophilin-2 isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC087311, AC087588
    8. NM_001407161.1NP_001394090.1  plakophilin-2 isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC087311, AC087588
      UniProtKB/TrEMBL
      A0A8V8TQD7
      Related
      ENST00000700564.1
    9. NM_001407162.1NP_001394091.1  plakophilin-2 isoform 9

      Status: REVIEWED

      Source sequence(s)
      AC087311, AC087588
      UniProtKB/TrEMBL
      A0A8V8TQD7
    10. NM_004572.4NP_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:675804
      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:388424
      ARM; armadillo repeat [structural motif]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      32790755..32896777 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      32667065..32772770 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)