GPC3 (glypican 3)

Gene

• Entrez ID: 2719
• Gene name: Glypican 3
• Gene symbol: GPC3
• Synonyms: DGSX, GTR2-2, MXR7, OCI-5, SDYS, SGB, SGBS, SGBS1
• Chromosome: X
• Chromosome location: Xq26.2
• Summary: Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. The protein encoded by this gene can bind to and inhibit the dipeptidyl peptidase activity of CD26, and it can induce apoptosis in certain cell types. Deletion mutations in this gene are associated with Simpson-Golabi-Behmel syndrome, also known as Simpson dysmorphia syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894854	A>T	Pathogenic	Coding sequence variant, missense variant
rs104894855	G>A	Pathogenic	Coding sequence variant, stop gained
rs122453119	G>A	Pathogenic	Coding sequence variant, missense variant
rs122453120	C>T	Pathogenic	Coding sequence variant, missense variant, genic downstream transcript variant
rs122453121	G>A	Pathogenic	Coding sequence variant, stop gained
rs138450923	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs141100113	C>A,T	Likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs267606850	C>T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant
rs398124166	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs745968470	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, genic downstream transcript variant, coding sequence variant
rs753210097	G>A,T	Likely-pathogenic, likely-benign	Synonymous variant, coding sequence variant, stop gained, genic downstream transcript variant
rs869025181	CCCTTAGGGAGAC>-	Pathogenic	Intron variant, frameshift variant, coding sequence variant
rs869025182	C>A	Pathogenic	Splice donor variant
rs869025183	C>T	Pathogenic	Intron variant, splice donor variant
rs886039384	AT>-	Pathogenic	Intron variant, frameshift variant, coding sequence variant
rs886039473	G>-	Pathogenic	Genic downstream transcript variant, frameshift variant, coding sequence variant
rs886039489	C>T	Pathogenic	Splice donor variant
rs886039908	A>-	Likely-pathogenic	Genic downstream transcript variant, frameshift variant, coding sequence variant
rs1057517739	C>A	Pathogenic	Coding sequence variant, stop gained
rs1556263859	G>A	Likely-pathogenic	Stop gained, coding sequence variant
rs1556297749	CTGGGTCATAATAAGCTTGGGGAAAT>TGCAAG	Pathogenic	Frameshift variant, coding sequence variant
rs1569392947	C>A	Pathogenic	Coding sequence variant, stop gained, genic downstream transcript variant
rs1569408743	G>-	Pathogenic	Coding sequence variant, frameshift variant, genic downstream transcript variant
rs1569426054	G>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1602581162	->G	Pathogenic	Coding sequence variant, frameshift variant
rs1603240717	->A	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006231	hsa-miR-219a-5p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	22449976
MIRT053054	hsa-miR-520c-3p	Flow, Luciferase reporter assay, Western blot	23647462
MIRT053054	hsa-miR-520c-3p	Luciferase reporter assay, QRTPCR, Western blot	23607462
MIRT053054	hsa-miR-520c-3p	qRT-PCR, Western blot	27633306
MIRT437356	hsa-miR-1271-5p	Western blot	22865282

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001523	Process	Retinoid metabolic process	TAS
GO:0001658	Process	Branching involved in ureteric bud morphogenesis	IEA
GO:0005515	Function	Protein binding	IPI	17549790, 29162697
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005796	Component	Golgi lumen	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	TAS
GO:0006024	Process	Glycosaminoglycan biosynthetic process	TAS
GO:0006027	Process	Glycosaminoglycan catabolic process	TAS
GO:0009617	Process	Response to bacterium	IEA
GO:0009653	Process	Anatomical structure morphogenesis	TAS	8589713
GO:0009948	Process	Anterior/posterior axis specification	IEA
GO:0009986	Component	Cell surface	IBA	21873635
GO:0010171	Process	Body morphogenesis	IEA
GO:0010466	Process	Negative regulation of peptidase activity	IEA
GO:0016477	Process	Cell migration	IBA	21873635
GO:0030282	Process	Bone mineralization	IEA
GO:0030316	Process	Osteoclast differentiation	IEA
GO:0030324	Process	Lung development	IEA
GO:0030513	Process	Positive regulation of BMP signaling pathway	IEA
GO:0031226	Component	Intrinsic component of plasma membrane	TAS
GO:0035116	Process	Embryonic hindlimb morphogenesis	IEA
GO:0042074	Process	Cell migration involved in gastrulation	ISS
GO:0043202	Component	Lysosomal lumen	TAS
GO:0043687	Process	Post-translational protein modification	TAS
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0045732	Process	Positive regulation of protein catabolic process	ISS
GO:0045807	Process	Positive regulation of endocytosis	ISS
GO:0045879	Process	Negative regulation of smoothened signaling pathway	ISS
GO:0045880	Process	Positive regulation of smoothened signaling pathway	IEA
GO:0045926	Process	Negative regulation of growth	IEA
GO:0046326	Process	Positive regulation of glucose import	IEA
GO:0046658	Component	Anchored component of plasma membrane	IBA	21873635
GO:0046658	Component	Anchored component of plasma membrane	ISS
GO:0050680	Process	Negative regulation of epithelial cell proliferation	IEA
GO:0060422	Function	Peptidyl-dipeptidase inhibitor activity	IDA	17549790
GO:0060828	Process	Regulation of canonical Wnt signaling pathway	IDA	14610063
GO:0060976	Process	Coronary vasculature development	ISS
GO:0062023	Component	Collagen-containing extracellular matrix	IEA
GO:0072111	Process	Cell proliferation involved in kidney development	ISS
GO:0072138	Process	Mesenchymal cell proliferation involved in ureteric bud development	ISS
GO:0072180	Process	Mesonephric duct morphogenesis	ISS
GO:0072203	Process	Cell proliferation involved in metanephros development	IEA
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IEA
GO:0090263	Process	Positive regulation of canonical Wnt signaling pathway	IBA	21873635
GO:0090263	Process	Positive regulation of canonical Wnt signaling pathway	IDA	24496449
GO:1905475	Process	Regulation of protein localization to membrane	IBA	21873635
GO:2000050	Process	Regulation of non-canonical Wnt signaling pathway	IDA	14610063
GO:2000096	Process	Positive regulation of Wnt signaling pathway, planar cell polarity pathway	IEA

Other IDs

• MIM: 300037
• HGNC: 4451
• e!Ensembl: ENSG00000147257

Protein

• UniProt ID: P51654
• Protein name: Glypican-3 (GTR2-2) (Intestinal protein OCI-5) (MXR7) [Cleaved into: Glypican-3 alpha subunit; Glypican-3 beta subunit]
• Protein function: Cell surface proteoglycan that bears heparan sulfate (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for binding to hedgehog proteins (By similarity). Binding to the hedgehog protein SHH triggers internalization of the complex by endocytosis and its subsequent lysosomal degradation (By similarity). Positively regulates the canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled and stimulating the binding of the Frizzled receptor to Wnt ligands (PubMed:16227623, PubMed:24496449). Positively regulates the non-canonical Wnt signaling pathway (By similarity). Binds to CD81 which decreases the availability of free CD81 for binding to the transcriptional repressor HHEX, resulting in nuclear translocation of HHEX and transcriptional repression (By similarity). Inhibits the dipeptidyl peptidase activity of DPP4 (PubMed:17549790). Plays a role in limb patterning and skeletal development by controlling the cellular response to BMP4 (By similarity). Modulates the effects of growth factors BMP2, BMP7 and FGF7 on renal branching morphogenesis (By similarity). Required for coronary vascular development (By similarity). Plays a role in regulating cell movements during gastrulation (By similarity).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01153	Glypican	14 → 578	Glypican	Family

• Sequence:

  MAGTVRTACLVVAMLLSLDFPGQAQPPPPPPDATCHQVRSFFQRLQPGLKWVPETPVPGS
  DLQVCLPKGPTCCSRKMEEKYQLTARLNMEQLLQSASMELKFLIIQNAAVFQEAFEIVVR
  HAKNYTNAMFKNNYPSLTPQAFEFVGEFFTDVSLYILGSDINVDDMVNELFDSLFPVIYT
  QLMNPGLPDSALDINECLRGARRDLKVFGNFPKLIMTQVSKSLQVTRIFLQALNLGIEVI
  NTTDHLKFSKDCGRMLTRMWYCSYCQGLMMVKPCGGYCNVVMQGCMAGVVEIDKYWREYI
  LSLEELVNGMYRIYDMENVLLGLFSTIHDSIQYVQKNAGKLTTTIGKLCAHSQQRQYRSA
  YYPEDLFIDKKVLKVAHVEHEETLSSRRRELIQKLKSFISFYSALPGYICSHSPVAENDT
  LCWNGQELVERYSQKAARNGMKNQFNLHELKMKGPEPVVSQIIDKLKHINQLLRTMSMPK
  GRVLDKNLDEEGFESGDCGDDEDECIGGSGDGMIKVKNQLRFLAELAYDLDVDDAPGNSQ
  QATPKDNEISTFHNLGNVHSPLKLLTSMAISVVCFFFLVH

• Sequence length: 580