The gene spans more than 500 kb of DNA consisting of 8 exons.

2.2kb mRNA; 1740 bp open reading frame.

580 amino acids; 65 kDa protein. GPC3 is a heparan sulfate proteoglycan (HSPG) that is attached to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor.

GPC3 is highly expressed in embryonal tissues such as the developing intestine and the mesoderm-derived tissues, and its expression is downregulated in most adult tissue.

Attached to the membrane by a GPI anchor.

The biochemical function of GPC3 has yet to be established. HSPG may be involved in the suppression/modulation of growth in the predominantly mesodermal tissues and organs; may play a role in the modulation of IGF-II interactions with its receptor and thereby modulate its function; can have a potential role as a regulator of growth and tumor predisposition. Therefore it is likely that GPC3 is able not only to bind more than one growth factor, but also to functionally affect the signalling of different growth factors. A role for GPC3 in the regulation of insulin-like growth (IGF) factors has been proposed. IGF-II is a growth factor that can act as a survival factor in the early stages of tumourigenesis. The co-expression of GPC3 and IGF-II has been observed in embryonal tumors as well as in mouse foetal tissues; GPC3 expression is able to induce apoptosis in a cell-specific manner, but this effect could be reversed by the addition of IGF peptides; IGFs could be needed to prevent GPC3-induced apoptosis in any cell, allowing cellular responses to other factors to take place and be mediated, enhanced or inhibited by GPC3; GPC3 mutations lead to SGBS (see below), a syndrome that shares significant similarities with the Beckwith-Wiedemann syndrome that is an overgrowth syndrome that is thought to be associated with increased expression of IGF2.

Belongs to the glypican family; six members, glypican-1 to 6, have been identified in mammalians; the protein core of glypicans are 20-50% identical; The glypican family is represented by at least two known members in Drosophila, dally and dally-like.

Most known mutations are deletions involving different exons of GPC3; missense, nonsense as well as splicing site mutations.

The expression of GPC3 is altered in cancer cells. GPC3 is upregulated in hepatocellular carcinoma, in Wilms tumor and in metastatics colorectal malignancie. With regard to tumours with neuronal phenotype, GPC3 was detected at variable levels in a neurofibrosarcoma and in most neuroblastomas, but was absent from medulloblastomas. These findings suggest that GPC3 expression is differentially regulated in the various cell lineages giving rise to pediatric tumours of the peripheral and central nervous systems. On the other hand, GPC3 is frequently silenced in mesotheliomas, in ovarian cancer cell lines and in breast cancer, often due to hypermethylation of the GPC3 promoter.