GPC4 (Glypican 4): A Key Heparan Sulfate Proteoglycan in Development and Disease
Comprehensive genomic and proteomic overview of GPC4, including its role in Simpson-Golabi-Behmel syndrome, cancer, and Wnt signaling.
Gene Information Card
| Symbol | GPC4 |
|---|---|
| Full Name | Glypican 4 |
| Gene Type | protein-coding |
| Chromosomal Location | Xq26.2 |
| NCBI Gene ID | 2239 ncbi.nlm.nih.gov/gene/2239 |
| Ensembl ID | ENSG00000176749 |
| UniProt ID | O75487 |
| OMIM ID | 300168 |
| HGNC ID | 4452 |
| Aliases | K-glypican, GPC-4, glypican-4 |
Description
GPC4 encodes glypican 4, a member of the glypican family of heparan sulfate proteoglycans. Glypican 4 is attached to the cell surface via a glycosylphosphatidylinositol (GPI) anchor and plays critical roles in cell growth, differentiation, and morphogenesis by modulating signaling pathways such as Wnt, Hedgehog, and fibroblast growth factor (FGF). Mutations in GPC4 are associated with Simpson-Golabi-Behmel syndrome type 1 (SGBS1), and altered expression is observed in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Simpson-Golabi-Behmel syndrome type 1 (SGBS1) | Loss-of-function mutations in GPC4 disrupt heparan sulfate proteoglycan signaling, leading to overgrowth and developmental abnormalities. | OMIM #300168; PMID: 10577907 |
| Wilms tumor | Reduced GPC4 expression may contribute to tumorigenesis by altering Wnt signaling. | PMID: 11532990 |
| Hepatocellular carcinoma | GPC4 overexpression promotes tumor growth via activation of Wnt/β-catenin pathway. | PMID: 29367642 |
| Breast cancer | GPC4 upregulation correlates with poor prognosis and enhanced cell proliferation. | PMID: 31073084 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Liver | 6.1 | Low |
| Lung | 4.7 | Low |
| Heart | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in embryonic kidney cells |
| HepG2 | 9.8 | Moderate expression in liver cancer cells |
| MCF7 | 7.4 | Moderate expression in breast cancer cells |
| A549 | 5.1 | Low expression in lung cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon; likely loss-of-function |
| c.497G>A (p.Arg166His) | Missense | <0.01% | Associated with SGBS1; disrupts heparan sulfate attachment |
| c.1030C>T (p.Arg344*) | Nonsense | <0.01% | Premature stop; loss-of-function in SGBS1 |
| c.1234_1235insA (p.Thr412Asnfs*5) | Frameshift | <0.01% | Frameshift leading to truncated protein |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg344*, p.Thr412Asnfs*5) result in truncated or absent glypican 4, reducing heparan sulfate proteoglycan activity and disrupting developmental signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in GPC4; overexpression in cancer may mimic gain-of-function effects.
Dominant Negative (DN)
No dominant-negative mutations described for GPC4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• Hedgehog signaling pathway (Reactome: R-HSA-5358351)
• FGF signaling pathway (Reactome: R-HSA-190236)
• Glypican pathway (Reactome: R-HSA-365623)
Protein Summary
Glypican 4 (UniProt O75487) is a 556-amino acid heparan sulfate proteoglycan anchored to the plasma membrane via a GPI anchor. It contains a core protein with three heparan sulfate chains attached to serine residues. Glypican 4 modulates cell signaling by binding to growth factors and morphogens, particularly Wnt and Hedgehog, thereby regulating cell proliferation, differentiation, and tissue patterning. Its expression is developmentally regulated, and dysregulation contributes to overgrowth syndromes and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPC4 Knockout HEK293 Cell Line | EDJ-KQ2996 | Human | 2239 | Details Get a Quote |
| GPC4 Knockout HCT 116 Cell Line | EDJ-KQ24189 | Human | 2239 | Details Get a Quote |
| GPC4 Knockout HeLa Cell Line | EDJ-KQ53216 | Human | 2239 | Details Get a Quote |
| GPC4 Knockout A-549 Cell Line | EDJ-KQ61697 | Human | 2239 | Details Get a Quote |
