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FLASH GENE

Symbol

GPC3

contributors: mct - updated : 25-10-2016

HGNC name	glypican 3
HGNC id	4451

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004484 8 - 2329 NP_004475 65.4 580 - 2008 18785116 NM_001164619 7 - 2167 NP_001158091 - 526 - 2008 18785116 NM_001164618 8 - 2281 NP_001158090 - 564 - 2008 18785116 NM_001164617 9 - 2398 NP_001158089 - 603 - 2008 18785116

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic spleen         Cardiovascular heart       highly Digestive liver       highly   mouth tongue     highly Endocrine pancreas         Lymphoid/Immune thymus         Reproductive female system ovary         female system placenta     highly Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer digestive liver anti-glypican 3 antibody against the C-terminal 30-kDa fragment such as GC33 are useful in therapy targeting hepatocellular carcinoma cancer muscle   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