GPC3 (Glypican 3): A Key Regulator in Development and Cancer
Comprehensive gene card, expression, mutations, and clinical relevance of GPC3
Gene Information Card
| Symbol | GPC3 |
|---|---|
| Full Name | Glypican 3 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq26.2 |
| NCBI Gene ID | 2719 ncbi.nlm.nih.gov/gene/2719 |
| Ensembl ID | ENSG00000147257 |
| UniProt ID | P51654 |
| OMIM ID | 300037 |
| HGNC ID | 4451 |
| Aliases | DGSX, MXR7, SDYS, SGB, SGBS, OCI-5 |
Description
GPC3 encodes glypican 3, a cell-surface heparan sulfate proteoglycan that regulates growth factor signaling, particularly Wnt and Hedgehog pathways. It plays critical roles in embryonic development and is frequently overexpressed in hepatocellular carcinoma and other cancers, while germline mutations cause Simpson-Golabi-Behmel syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Simpson-Golabi-Behmel syndrome | Loss-of-function mutations in GPC3 lead to dysregulation of growth factor signaling, causing overgrowth and multiple congenital anomalies. | OMIM 300037; ClinVar |
| Hepatocellular carcinoma | GPC3 is overexpressed in HCC tissues and promotes tumor growth via Wnt signaling activation. | COSMIC; multiple studies |
| Wilms tumor | GPC3 expression is elevated in some Wilms tumors, suggesting an oncogenic role. | COSMIC; literature |
| Ovarian cancer | GPC3 overexpression is observed in certain ovarian cancer subtypes and may contribute to proliferation. | COSMIC; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 0.1 | Not detected |
| Kidney | 0.2 | Not detected |
| Lung | 0.1 | Not detected |
| Testis | 0.1 | Not detected |
| Placenta | 0.1 | Not detected |
| Fetal liver | High | Expressed during development |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | High | Hepatocellular carcinoma cell line |
| Huh-7 | High | Hepatocellular carcinoma cell line |
| SK-HEP-1 | Low | Hepatocellular carcinoma cell line |
| MCF7 | Low | Breast cancer cell line |
| A549 | Low | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1186C>T (p.Arg396*) | Nonsense | Rare | Loss of function; associated with SGBS |
| c.1129C>T (p.Arg377*) | Nonsense | Rare | Loss of function; associated with SGBS |
| c.1169G>A (p.Trp390*) | Nonsense | Rare | Loss of function; associated with SGBS |
| c.1327delC (p.Leu443Trpfs*26) | Frameshift | Rare | Loss of function; associated with SGBS |
| c.1553G>A (p.Trp518*) | Nonsense | Rare | Loss of function; associated with SGBS |
Mutation functional classification
Loss of Function (LOF)
Germline loss-of-function mutations cause Simpson-Golabi-Behmel syndrome, characterized by pre- and postnatal overgrowth, distinctive facial features, and organomegaly.
Gain of Function (GOF)
Somatic overexpression (not mutations) is common in cancers, acting as an oncogene via Wnt signaling.
Dominant Negative (DN)
Not reported for GPC3.
View complete mutation data：
Gene Ontology (GO)
| • heparan sulfate proteoglycan binding | • growth factor binding |
| • Wnt-protein binding | • extracellular matrix organization |
| • cell proliferation | • negative regulation of cell growth |
| • positive regulation of canonical Wnt signaling pathway | • embryonic skeletal system morphogenesis |
Pathways
• Wnt signaling pathway
• Hedgehog signaling pathway
• Proteoglycan metabolism
Protein Summary
Glypican 3 is a 70 kDa core protein with heparan sulfate chains, anchored to the cell membrane via glycosylphosphatidylinositol (GPI). It modulates growth factor signaling, particularly Wnt and Hedgehog, and is cleaved by furin to release a soluble N-terminal fragment. In adults, expression is low, but it is highly expressed in fetal tissues and many cancers, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPC3 Knockout HEK293 Cell Line | EDJ-KQ17714 | Human | 2719 | Details Get a Quote |
| GPC3 Knockout HCT 116 Cell Line | EDJ-KQ19786 | Human | 2719 | Details Get a Quote |
| GPC3 Knockout HeLa Cell Line | EDJ-KQ53353 | Human | 2719 | Details Get a Quote |
| GPC3 Knockout A-549 Cell Line | EDJ-KQ61832 | Human | 2719 | Details Get a Quote |
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