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FLASH GENE
Symbol GPC3 contributors: mct - updated : 25-10-2016
HGNC name glypican 3
HGNC id 4451
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
blood / hematopoieticspleen    
Cardiovascularheart   highly
Digestiveliver   highly
 mouthtongue  highly
Endocrinepancreas    
Lymphoid/Immunethymus    
Reproductivefemale systemovary   
 female systemplacenta  highly
Respiratorylung    
Urinarykidney    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialsecretoryglandularendocrine 
Lymphoid    
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text spleen, placenta, peak expression during development and down-regulated in all tissues after birth (Boily 2007)
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a glycosyl phosphatidylinositol anchor, with 13 cysteines at conserved position
  • HOMOLOGY
    interspecies homolog to murine Gpc3
    Homologene
    FAMILY
  • glypican family
  • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,lysosome
    text
  • attached to the cell surface by a glycosylphosphatidylinositol anchor
  • basic FUNCTION
  • heparan sulfate proteoglycans that are anchored to the cell membrane by a glycosyl-phosphatidylinositol protein
  • involved in growth control in embryonic mesodermal tissues
  • putative modulator of IGF2, juxtaposed to GPC4, with tumor suppressor activity in malignant mesothelioma or other tumors
  • plays a negative role in cell proliferation and an apoptosis-inducing role in specific tissues
  • may play roles in glucose transport through SLC2A4
  • may play a role in insulin stimulated glucose uptake
  • cell surface proteoglycans, with expression highly tissue- and stage-specific during human development
  • confers oncogenecity through the interaction between IGF2 and its receptor, and the subsequent activation of the IGF-signaling pathway
  • plays a critical role in promoting hepatocellular carcinoma cell growth and differentiation
  • heparan sulfate proteoglycan that has an important role in cell growth and differentiation, and its function in tumorigenesis is tissue-dependent
  • down-regulates cell proliferation by binding to HH and down-regulating the HH signaling pathway and binding with CD81, thus making it unavailable to bind to HHEX and causing its nuclear translocation
  • CELLULAR PROCESS cell life, cell death/apoptosis
    cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • proteoglycan putative constituent of extracellular matrix complexing with IGF2
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • SLC2A4-binding protein (GPC3 and SLC2A4 co-localizes at the plasma membrane in response to insulin)
  • binds to and inhibits the dipeptidyl peptidase activity of DPP4
  • plays a role in glucose transport by interacting with SLC2A1
  • is a transcriptional target of MYC and the expression of MYC is also regulated by GPC3, thus forming a positive feedback signaling loop
  • CD81 is a binding partner for GPC3, and its expression and co-localization with GPC3 increased at the end of hepatocyte proliferation
  • ZHX2 suppresses GPC3 transcription by binding with its core promoter and reduced nucleic ZHX2 expression may be involved in GPC3 reactivation inhepatocellular carcinoma (HCC)
  • cell & other
    REGULATION
    Other regulated by NFYA, NFYB, NFYC and others cell type-specific factors (may play an important role in the regulation of GPC3)
    ASSOCIATED DISORDERS
    corresponding disease(s) SGBS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in mesothelioma, breast and ovarian cancer
    tumoral     --over  
    in hepatocellular carcinoma (HCC), neuroblastoma and Wilm's tumor cells
    tumoral     --low  
    in intrahepatic chanlangiocarcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • specific immunomarker for HCC that can be used to distinguish HCC from benign hepatocellular mass lesions, particularly hepatocellular adenoma , but combination of AFP and GPC3 can elevate the sensitivity of diagnosis
  • may have future application as a biomarker for rhabdomyosarcomas
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    anti-glypican 3 antibody against the C-terminal 30-kDa fragment such as GC33 are useful in therapy targeting hepatocellular carcinoma
    cancermuscle 
    may be a therapeutic target in rhabdomyosarcomas (RMS), the most common paediatric soft tissue sarcomas
    ANIMAL & CELL MODELS
  • Gpc3-deficient mice display a high incidence of congenital cardiac malformations like ventricular septal defects, common atrioventricular canal and double outlet right ventricle