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PLAG1 (Pleomorphic adenoma gene 1)

Written2002-06David Gisselsson
Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

(Note : for Links provided by Atlas : click)

Identity

HGNC (Hugo) PLAG1
HGNC Alias symbZNF912
HGNC Previous namepleiomorphic adenoma gene 1
LocusID (NCBI) 5324
Atlas_Id 74
Location 8q12.1  [Link to chromosome band 8q12]
Location_base_pair Starts at 56160909 and ends at 56211273 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PLAG1.png]
Local_order (316 cR / 86 Mb from 8pter)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CHCHD7 (8q12.1)::PLAG1 (8q12.1)COL1A2 (7q21.3)::PLAG1 (8q12.1)COL3A1 (2q32.2)::PLAG1 (8q12.1)
CTNNB1 (3p22.1)::PLAG1 (8q12.1)FGFR1 (8p11.23)::PLAG1 (8q12.1)HAS2 (8q24.13)::PLAG1 (8q12.1)
LIFR (5p13.1)::PLAG1 (8q12.1)PLAG1 (8q12.1)::CHCHD7 (8q12.1)PLAG1 (8q12.1)::CTNNB1 (3p22.1)
PLAG1 (8q12.1)::HACD4 (9p21.3)PLAG1 (8q12.1)::HAS2 (8q24.13)PLAG1 (8q12.1)::LIFR (5p13.1)
PLAG1 (8q12.1)::RPS4Y1 (Yp11.2)PLAG1 (8q12.1)::RPS4Y1 (Yp11.31)PLAG1 (8q12.1)::TCEA1 (8q11.23)
PLAG1 (8q12.1)::TRBJ2-7 (7q34)RAB2A (8q12.1)::PLAG1 (8q12.1)RAD51B (14q24.1)::PLAG1 (8q12.1)
TCEA1 (8q11.23)::PLAG1 (8q12.1)

DNA/RNA

 
  Schematic view of the gene with approximate sizes of introns (kb) and exons (bp); the coding region (violet) translates into a 500 amino acid product with three functional subunits.
Description 7313 bp, 5 exons, 4 introns
Transcription At least two splicing variants, including and excluding the second exon

Protein

Description 500 amino acids with at least three functional regions : 1. Two N-terminal nuclear localisation signals, 2. Seven canonical zinc-finger domains, 3. A serine rich C-terminus
Expression Heart, placenta, spleen, prostate, testis, ovary, small intestine, several tumours
Localisation Nuclear
Function One of the N-terminal nuclear localisation signals (NLS1) interacts with karyopherin a2, which escorts proteins into the nucleus. Three of the seven Zn-finger domains are responsible for interaction with DNA and PLAG1 specifically activates transcription from its consensus binding site. Potential PLAG1 binding sites have been found in the promoter of IGF2.
Homology Mouse and rat Plag1

Mutations

Somatic Involved in chromosome rearrangements in epithelial and mesenchymal tumours. These are typically complex structural abnormalities, resulting in an exchange of regulatory elements and abnormal expression of PLAG1.

Implicated in

Note
  
Entity
Disease Benign epithelial tumour
Prognosis Recovery after surgical removal
Cytogenetics The most common breakpoints are 3p21, 8q12, and 12q15
Hybrid/Mutated Gene The following translocations have been reported to result in hybrid genes involving PLAG1:
  • t(3;8)(p21;q12): CTNNB1 CTNNB1/PLAG1
  • t(5;8)(p13;q12): LIFR/PLAG1
  • Also, rearrangements between PLAG1 and TCEA1 have been detected in cases with normal karyotypes.
  • Abnormal Protein Fusions occur in the 5' regulatory regions, leading to promoter swapping and activation of PLAG1 expression while preserving coding sequences.
      
      
    Entity Carcinoma ex pleomorphic adenoma
    Disease Malignant epithelial tumour arising from pleomorphic adenoma
    Prognosis 30% five-year survival
    Cytogenetics Complex karyotype including t(3;8)(p23;q12)
    Hybrid/Mutated Gene Intragenic PLAG1 rearrangements demonstrated by fluorescence in situ hybridisation.
      
      
    Entity Lipoblastoma
    Disease Benign fat-forming tumour of childhood
    Prognosis Recovery after surgical removal
    Cytogenetics Structural abnormalities involving 8q11-13
    Hybrid/Mutated Gene The following rearrangements have been reported to result in hybrid genes involving PLAG1:
  • del(8)(q12q24), r(8): HAS2/PLAG1
  • t(7;8)(p22;q13): COL1A2/HAS2
  • Abnormal Protein Fusions occur in the 5' regulatory regions, leading promoter swapping and activation of PLAG1 expression while preserving coding sequences.
      

    Breakpoints

     

    Bibliography

    Conserved mechanism of PLAG1 activation in salivary gland tumors with and without chromosome 8q12 abnormalities: identification of SII as a new fusion partner gene.
    Aström AK, Voz ML, Kas K, Röijer E, Wedell B, Mandahl N, Van de Ven W, Mark J, Stenman G
    Cancer research. 1999 ; 59 (4) : 918-923.
    PMID 10029085
     
    Evidence of involvement of the PLAG1 gene in lipoblastomas.
    Astrom A, D'Amore ES, Sainati L, Panarello C, Morerio C, Mark J, Stenman G
    International journal of oncology. 2000 ; 16 (6) : 1107-1110.
    PMID 10811981
     
    Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal.
    Braem CV, Kas K, Meyen E, Debiec-Rychter M, Van De Ven WJ, Voz ML
    The Journal of biological chemistry. 2002 ; 277 (22) : 19673-19678.
    PMID 11882654
     
    Histologic localization of PLAG1 (pleomorphic adenoma gene 1) in pleomorphic adenoma of the salivary gland: cytogenetic evidence of common origin of phenotypically diverse cells.
    Debiec-Rychter M, Van Valckenborgh I, Van den Broeck C, Hagemeijer A, Van de Ven WJ, Kas K, Van Damme B, Voz ML
    Laboratory investigation; a journal of technical methods and pathology. 2001 ; 81 (9) : 1289-1297.
    PMID 11555676
     
    Expression of PLAG1 and HMGIC proteins and fusion transcripts in radiation-associated pleomorphic adenomas.
    Enlund F, Nordkvist A, Sahlin P, Mark J, Stenman G
    International journal of oncology. 2002 ; 20 (4) : 713-716.
    PMID 11894114
     
    PLAG1 alterations in lipoblastoma: involvement in varied mesenchymal cell types and evidence for alternative oncogenic mechanisms.
    Gisselsson D, Hibbard MK, Dal Cin P, Sciot R, Hsi BL, Kozakewich HP, Fletcher JA
    The American journal of pathology. 2001 ; 159 (3) : 955-962.
    PMID 11549588
     
    The tumorigenic diversity of the three PLAG family members is associated with different DNA binding capacities.
    Hensen K, Van Valckenborgh IC, Kas K, Van de Ven WJ, Voz ML
    Cancer research. 2002 ; 62 (5) : 1510-1517.
    PMID 11888928
     
    PLAG1 fusion oncogenes in lipoblastoma.
    Hibbard MK, Kozakewich HP, Dal Cin P, Sciot R, Tan X, Xiao S, Fletcher JA
    Cancer research. 2000 ; 60 (17) : 4869-4872.
    PMID 10987300
     
    Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH.
    Jin C, Martins C, Jin Y, Wiegant J, Wennerberg J, Dictor M, Gisselsson D, Strömbeck B, Fonseca I, Mitelman F, Tanke HJ, Höglund M, Mertens F
    Genes, chromosomes & cancer. 2001 ; 30 (2) : 161-167.
    PMID 11135432
     
    A 2-Mb YAC contig and physical map covering the chromosome 8q12 breakpoint cluster region in pleomorphic adenomas of the salivary glands.
    Kas K, Röijer E, Voz M, Meyen E, Stenman G, Van de Ven WJ
    Genomics. 1997 ; 43 (3) : 349-358.
    PMID 9268638
     
    Transcriptional activation capacity of the novel PLAG family of zinc finger proteins.
    Kas K, Voz ML, Hensen K, Meyen E, Van de Ven WJ
    The Journal of biological chemistry. 1998 ; 273 (36) : 23026-23032.
    PMID 9722527
     
    Pleomorphic adenoma gene 1 is expressed in cultured benign and malignant salivary gland tumor cells.
    Queimado L, Lopes C, Du F, Martins C, Bowcock AM, Soares J, Lovett M
    Laboratory investigation; a journal of technical methods and pathology. 1999 ; 79 (5) : 583-589.
    PMID 10334569
     
    Fluorescence in situ hybridization mapping of breakpoints in pleomorphic adenomas with 8q12-13 abnormalities identifies a subgroup of tumors without PLAG1 involvement.
    Röijer E, Kas K, Behrendt M, Van de Ven W, Stenman G
    Genes, chromosomes & cancer. 1999 ; 24 (1) : 78-82.
    PMID 9892112
     
    Assignment of the rat pleiomorphic adenoma genes (Plag1, Plagl1, Plagl2) by in situ hybridization and radiation hybrid mapping.
    Szpirer C, Kas K, Laes JF, Rivière M, Van Vooren P, Szpirer J
    Cytogenetics and cell genetics. 2001 ; 94 (1-2) : 94-95.
    PMID 11701966
     
    PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II.
    Voz ML, Agten NS, Van de Ven WJ, Kas K
    Cancer research. 2000 ; 60 (1) : 106-113.
    PMID 10646861
     
    The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter.
    Voz ML, Aström AK, Kas K, Mark J, Stenman G, Van de Ven WJ
    Oncogene. 1998 ; 16 (11) : 1409-1416.
    PMID 9525740
     
    First insights into the molecular basis of pleomorphic adenomas of the salivary glands.
    Voz ML, Van de Ven WJ, Kas K
    Advances in dental research. 2000 ; 14 : 81-83.
    PMID 11842929
     

    Citation

    This paper should be referenced as such :
    Gisselsson, D
    PLAG1 (pleomorphic adenoma gene 1)
    Atlas Genet Cytogenet Oncol Haematol. 2002;6(4):285-287.
    Free journal version : [ pdf ]   [ DOI ]


    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
      t(7;8)(q34;q12) PLAG1::TRBJ2-7


    External links

     

    Nomenclature
    HGNC (Hugo)PLAG1   9045
    Cards
    AtlasPLAG1ID74
    Entrez_Gene (NCBI)PLAG1    PLAG1 zinc finger
    AliasesPSA; SGPA; SRS4; ZNF912
    GeneCards (Weizmann)PLAG1
    Ensembl hg19 (Hinxton)ENSG00000181690 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000181690 [Gene_View]  ENSG00000181690 [Sequence]  chr8:56160909-56211273 [Contig_View]  PLAG1 [Vega]
    ICGC DataPortalENSG00000181690
    TCGA cBioPortalPLAG1
    AceView (NCBI)PLAG1
    Genatlas (Paris)PLAG1
    SOURCE (Princeton)PLAG1
    Genetics Home Reference (NIH)PLAG1
    Genomic and cartography
    GoldenPath hg38 (UCSC)PLAG1  -     chr8:56160909-56211273 -  8q12.1   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)PLAG1  -     8q12.1   [Description]    (hg19-Feb_2009)
    GoldenPathPLAG1 - 8q12.1 [CytoView hg19]  PLAG1 - 8q12.1 [CytoView hg38]
    ImmunoBaseENSG00000181690
    Genome Data Viewer NCBIPLAG1 [Mapview hg19]  
    OMIM181030   603026   618907   
    Gene and transcription
    Genbank (Entrez)AB209131 AF221549 AF221550 AK296933 AK313663
    RefSeq transcript (Entrez)NM_001114634 NM_001114635 NM_002655
    Consensus coding sequences : CCDS (NCBI)PLAG1
    Gene ExpressionPLAG1 [ NCBI-GEO ]   PLAG1 [ EBI - ARRAY_EXPRESS ]   PLAG1 [ SEEK ]   PLAG1 [ MEM ]
    Gene Expression Viewer (FireBrowse)PLAG1 [ Firebrowse - Broad ]
    GenevisibleExpression of PLAG1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)5324
    GTEX Portal (Tissue expression)PLAG1
    Human Protein AtlasENSG00000181690-PLAG1 [pathology]   [cell]   [tissue]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ6DJT9   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ6DJT9  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ6DJT9
    PhosPhoSitePlusQ6DJT9
    Domaine pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
    Domains : Interpro (EBI)PLAG1/PLAGL2    Znf_C2H2_sf    Znf_C2H2_type   
    Domain families : Pfam (Sanger)zf-C2H2 (PF00096)   
    Domain families : Pfam (NCBI)pfam00096   
    Domain families : Smart (EMBL)ZnF_C2H2 (SM00355)  
    Conserved Domain (NCBI)PLAG1
    SuperfamilyQ6DJT9
    AlphaFold pdb e-kbQ6DJT9   
    Human Protein Atlas [tissue]ENSG00000181690-PLAG1 [tissue]
    HPRD04321
    Protein Interaction databases
    DIP (DOE-UCLA)Q6DJT9
    IntAct (EBI)Q6DJT9
    BioGRIDPLAG1
    STRING (EMBL)PLAG1
    ZODIACPLAG1
    Ontologies - Pathways
    QuickGOQ6DJT9
    Ontology : AmiGORNA polymerase II cis-regulatory region sequence-specific DNA binding  RNA polymerase II cis-regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  DNA-binding transcription factor activity  nucleoplasm  centrosome  cytosol  transcription, DNA-templated  regulation of transcription, DNA-templated  positive regulation of gene expression  negative regulation of gene expression  nuclear speck  gland morphogenesis  multicellular organism growth  positive regulation of transcription by RNA polymerase II  metal ion binding  positive regulation of glial cell proliferation  prostate gland growth  
    Ontology : EGO-EBIRNA polymerase II cis-regulatory region sequence-specific DNA binding  RNA polymerase II cis-regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  DNA-binding transcription factor activity  nucleoplasm  centrosome  cytosol  transcription, DNA-templated  regulation of transcription, DNA-templated  positive regulation of gene expression  negative regulation of gene expression  nuclear speck  gland morphogenesis  multicellular organism growth  positive regulation of transcription by RNA polymerase II  metal ion binding  positive regulation of glial cell proliferation  prostate gland growth  
    NDEx NetworkPLAG1
    Atlas of Cancer Signalling NetworkPLAG1
    Wikipedia pathwaysPLAG1
    Orthology - Evolution
    OrthoDB5324
    GeneTree (enSembl)ENSG00000181690
    Phylogenetic Trees/Animal Genes : TreeFamPLAG1
    Homologs : HomoloGenePLAG1
    Homology/Alignments : Family Browser (UCSC)PLAG1
    Gene fusions - Rearrangements
    Fusion : MitelmanCOL1A2::PLAG1 [7q21.3/8q12.1]  
    Fusion : MitelmanCOL3A1::PLAG1 [2q32.2/8q12.1]  
    Fusion : MitelmanCTNNB1::PLAG1 [3p22.1/8q12.1]  
    Fusion : MitelmanFGFR1::PLAG1 [8p11.23/8q12.1]  
    Fusion : MitelmanHAS2::PLAG1 [8q24.13/8q12.1]  
    Fusion : MitelmanLIFR::PLAG1 [5p13.1/8q12.1]  
    Fusion : MitelmanPLAG1::TRBJ2-7 [8q12.1/-]  
    Fusion : MitelmanRAB2A::PLAG1 [8q12.1/8q12.1]  
    Fusion : MitelmanRAD51B::PLAG1 [14q24.1/8q12.1]  
    Fusion : MitelmanTCEA1::PLAG1 [8q11.23/8q12.1]  
    Fusion : COSMICTCEA1 [8q11.23]  -  PLAG1 [8q12.1]  [fusion_1085]  [fusion_1090]  
    Fusion Cancer (Beijing)PLAG1 [8q12.1]  -  RPS4Y1 [Yp11.31]  [FUSC002071]
    Fusion : QuiverPLAG1
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerPLAG1 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)PLAG1
    dbVarPLAG1
    ClinVarPLAG1
    MonarchPLAG1
    1000_GenomesPLAG1 
    Exome Variant ServerPLAG1
    GNOMAD BrowserENSG00000181690
    Varsome BrowserPLAG1
    ACMGPLAG1 variants
    VarityQ6DJT9
    Genomic Variants (DGV)PLAG1 [DGVbeta]
    DECIPHERPLAG1 [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisPLAG1 
    Mutations
    ICGC Data PortalPLAG1 
    TCGA Data PortalPLAG1 
    Broad Tumor PortalPLAG1
    OASIS PortalPLAG1 [ Somatic mutations - Copy number]
    Cancer Gene: CensusPLAG1 
    Somatic Mutations in Cancer : COSMICPLAG1  [overview]  [genome browser]  [tissue]  [distribution]  
    Somatic Mutations in Cancer : COSMIC3DPLAG1
    Mutations and Diseases : HGMDPLAG1
    LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
    BioMutaPLAG1
    DgiDB (Drug Gene Interaction Database)PLAG1
    DoCM (Curated mutations)PLAG1
    CIViC (Clinical Interpretations of Variants in Cancer)PLAG1
    OncoKBPLAG1
    NCG (London)PLAG1
    Cancer3DPLAG1
    Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM181030    603026    618907   
    Orphanet23663   
    DisGeNETPLAG1
    MedgenPLAG1
    Genetic Testing Registry PLAG1
    NextProtQ6DJT9 [Medical]
    GENETestsPLAG1
    Target ValidationPLAG1
    Huge Navigator PLAG1 [HugePedia]
    ClinGenPLAG1
    Clinical trials, drugs, therapy
    MyCancerGenomePLAG1
    Protein Interactions : CTDPLAG1
    Pharm GKB GenePA33378
    PharosQ6DJT9
    Clinical trialPLAG1
    Miscellaneous
    canSAR (ICR)PLAG1
    HarmonizomePLAG1
    DataMed IndexPLAG1
    Probes
    Litterature
    PubMed86 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    EVEXPLAG1
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

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    indexed on : Fri Oct 8 21:25:18 CEST 2021

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