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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 580 | Xq26.2 | GPC3 | glypican 3 | |
| Mouse | - | 579 | X A5 | Gpc3 | glypican 3 | |
| Rat | - | 597 | Xq36 | Gpc3 | glypican 3 | |
| Gene and Protein Information Comments | ||||||
| The biological relevance of the different human protein isoforms identified is unclear. | ||||||
| Database Links |
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| Alphafold | P51654 (Hs), Q8CFZ4 (Mm), P13265 (Rn) |
| ChEMBL Target | CHEMBL4630889 (Hs) |
| Ensembl Gene | ENSG00000147257 (Hs), ENSMUSG00000055653 (Mm), ENSRNOG00000060179 (Rn) |
| Entrez Gene | 2719 (Hs), 14734 (Mm), 25236 (Rn) |
| Human Protein Atlas | ENSG00000147257 (Hs) |
| KEGG Gene | hsa:2719 (Hs), mmu:14734 (Mm), rno:25236 (Rn) |
| OMIM | 300037 (Hs) |
| Pharos | P51654 (Hs) |
| RefSeq Nucleotide | NM_001164617 (Hs), NM_016697 (Mm), NM_012774 (Rn) |
| RefSeq Protein | NP_001158089 (Hs), NP_057906 (Mm), NP_036906 (Rn) |
| UniProtKB | P51654 (Hs), Q8CFZ4 (Mm), P13265 (Rn) |
| Wikipedia | GPC3 (Hs) |
Download all structure-activity data for this target as a CSV file 
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| Physiological Consequences of Altering Gene Expression
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| Clinically-Relevant Mutations and Pathophysiology
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| Gene Expression and Pathophysiology Comments | |
| GPC3 expression can be used as a marker to distinguish hepatocellular carcinoma (GPC3+ve) from cirrhotic dysplasia (GPC3-ve) [1,10]. |
| General Comments |
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Glypican 3 (GPC3) is a glycosylphosphatidylinositol-anchored proteoglycan expressed during fetal development and with high frequency on the surface of cancer cells, but rarely on normal adult cells [2], making it an ideal target for anti-cancer therapies with minimal toxicity against normal tissue [7,9,12,15], i.e. minimising on-target off-tumor activity. Monoclonal antibodies directed at GPC3 are being developed as novel oncology drugs (e.g. Roche's codrituzumab). A bispecific mAb co-targeting GPC3 and the CD3 component of the T cell receptor complex (research code ERY974 [8]) is in Phase 1 clinical trial in patients with GPC3-positive advanced solid tumours (NCT02748837). ERY974 is an investigational cancer immunotherapy who's mechanism of action puts it in the family of mAbs referred to as T cell redirecting antibodies (or TRABs). ERY974 is designed to bring T cells in to close proximity with cancer cells to maximise antibody-activated killing capacity (both antibody induced and T cell directed) against the malignant cells. |
1. Anatelli F, Chuang ST, Yang XJ, Wang HL. (2008) Value of glypican 3 immunostaining in the diagnosis of hepatocellular carcinoma on needle biopsy. Am J Clin Pathol, 130 (2): 219-23. [PMID:18628090]
2. Baumhoer D, Tornillo L, Stadlmann S, Roncalli M, Diamantis EK, Terracciano LM. (2008) Glypican 3 expression in human nonneoplastic, preneoplastic, and neoplastic tissues: a tissue microarray analysis of 4,387 tissue samples. Am J Clin Pathol, 129 (6): 899-906. [PMID:18480006]
3. Bhave VS, Mars W, Donthamsetty S, Zhang X, Tan L, Luo J, Bowen WC, Michalopoulos GK. (2013) Regulation of liver growth by glypican 3, CD81, hedgehog, and Hhex. Am J Pathol, 183 (1): 153-9. [PMID:23665349]
4. Capurro MI, Xu P, Shi W, Li F, Jia A, Filmus J. (2008) Glypican-3 inhibits Hedgehog signaling during development by competing with patched for Hedgehog binding. Dev Cell, 14 (5): 700-11. [PMID:18477453]
5. Davoodi J, Kelly J, Gendron NH, MacKenzie AE. (2007) The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26. Proteomics, 7 (13): 2300-10. [PMID:17549790]
6. Filmus J, Capurro M. (2014) The role of glypicans in Hedgehog signaling. Matrix Biol, 35: 248-52. [PMID:24412155]
7. Ho M, Kim H. (2011) Glypican-3: a new target for cancer immunotherapy. Eur J Cancer, 47 (3): 333-8. [PMID:21112773]
8. Ishiguro T, Sano Y, Komatsu SI, Kamata-Sakurai M, Kaneko A, Kinoshita Y, Shiraiwa H, Azuma Y, Tsunenari T, Kayukawa Y et al.. (2017) An anti-glypican 3/CD3 bispecific T cell-redirecting antibody for treatment of solid tumors. Sci Transl Med, 9 (410). [PMID:28978751]
9. Ishiguro T, Sugimoto M, Kinoshita Y, Miyazaki Y, Nakano K, Tsunoda H, Sugo I, Ohizumi I, Aburatani H, Hamakubo T et al.. (2008) Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer. Cancer Res, 68 (23): 9832-8. [PMID:19047163]
10. Jakubovic BD, Jothy S. (2007) Glypican-3: from the mutations of Simpson-Golabi-Behmel genetic syndrome to a tumor marker for hepatocellular carcinoma. Exp Mol Pathol, 82 (2): 184-9. [PMID:17258707]
11. Khurana S, Margamuljana L, Joseph C, Schouteden S, Buckley SM, Verfaillie CM. (2013) Glypican-3-mediated inhibition of CD26 by TFPI: a novel mechanism in hematopoietic stem cell homing and maintenance. Blood, 121 (14): 2587-95. [PMID:23327927]
12. Nakano K, Ishiguro T, Konishi H, Tanaka M, Sugimoto M, Sugo I, Igawa T, Tsunoda H, Kinoshita Y, Habu K et al.. (2010) Generation of a humanized anti-glypican 3 antibody by CDR grafting and stability optimization. Anticancer Drugs, 21 (10): 907-16. [PMID:20847643]
13. Nakano K, Sugo I, Sugimoto M, Ishiguro T, Tanaka M, Iijima S. (2011) Anti-glypican 3 antibody having modified sugar chain. Patent number: US7867734 B2. Assignee: Chugai Pharmaceutical Co Ltd.. Priority date: 26/10/2004. Publication date: 11/01/2011.
14. Shi W, Filmus J. (2009) A patient with the Simpson-Golabi-Behmel syndrome displays a loss-of-function point mutation in GPC3 that inhibits the attachment of this proteoglycan to the cell surface. Am J Med Genet A, 149A (3): 552-4. [PMID:19215053]
15. Takai H, Kato A, Kinoshita Y, Ishiguro T, Takai Y, Ohtani Y, Sugimoto M, Suzuki M. (2009) Histopathological analyses of the antitumor activity of anti-glypican-3 antibody (GC33) in human liver cancer xenograft models: The contribution of macrophages. Cancer Biol Ther, 8 (10): 930-8. [PMID:19276671]
Tumour-associated antigens: glypican 3. Last modified on 30/06/2021. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2959.
