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glypican 3

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Target not currently curated in GtoImmuPdb

Target id: 2959

Nomenclature: glypican 3

Family: Tumour-associated antigens

Gene and Protein Information Click here for help
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 Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein

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Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
codrituzumab Peptide Primary target of this compound Hs Binding - - 12-13
Immuno Process Associations
Immuno Process:  Antigen presentation
Immuno Process:  Immune system development
Physiological Functions Click here for help
GPC3 can inhibit the dipeptidyl peptidase activity of CD26.
Species:  Human
References:  5,11
GPC3 acts as a negative regulator of Hedgehog (Hh) signaling during development.
Species:  Human
References:  3-4,6
Physiological Consequences of Altering Gene Expression Click here for help
Loss-of-function mutations in GPC3 permit hyperactivation of Hegdehog (Hh) signaling, that ultimately leads to overgrowth and cancer.
Species:  Human
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Simpson-Golabi-Behmel syndrome
Description: A rare X-linked recessive syndrome characterised by pre- and postnatal overgrowth, distinctive craniofacial features, variable congenital malformations, organomegaly and an increased tumour risk.
Synonyms: Golabi-Rosen syndrome
Simpson-Golabi-Behmel syndrome type 1
X-linked dysplasia gigantism syndrome
OMIM: 312870
Orphanet: ORPHA373
References:  14
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
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.


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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]

How to cite this page

Tumour-associated antigens: glypican 3. Last modified on 30/06/2021. Accessed on 19/06/2024. IUPHAR/BPS Guide to PHARMACOLOGY,