The reference OMIM entry for this protein is 300037

Glypican 3; gpc3
Oci-5, rat, homolog of

DESCRIPTION

Members of the glypican family, including GPC3, are heparan sulfate proteoglycans that bind to the exocytoplasmic surface of the plasma membrane through a covalent glycosylphosphatidylinositol (GPI) linkage. The main function of membrane-attached glypicans is to regulate the signaling of WNTs, Hedgehogs, fibroblast growth factors, and bone morphogenetic proteins (Filmus et al., 2008).

CLONING

To identify the molecular basis for Simpson-Golabi-Behmel syndrome (SGBS; see 312870), also called Simpson dysmorphia syndrome (SDYS), Pilia et al. (1996) adopted a positional cloning approach, using an X/autosome translocation. They used the cell line GM0097, which was deposited in the NIGMS repository in 1974. This cell line originated from a woman diagnosed with Beckwith-Wiedemann syndrome (BWS; 130650) and showed a karyotype with a de novo X;1 translocation. The karyotype suggested that she was affected by the X-linked SGBS rather than BWS, which is determined by a mutation on 11p. They mapped the breakpoint in an existing contig assembled across Xq26 and found a gene, called GPC3 by them, which was interrupted by this translocation. The gene was interrupted in another female patient with overgrowth and an X;16 translocation and exhibited deletions in 3 different SGBS families. The 2,130-bp cDNA encodes a deduced protein of 580 amino acids beginning 151 bp from the start of the sequence. GPC3 shares a number of features with the GPC1 gene (600395). Filmus et al., 1988 isolated rat Gpc3 as a transcript developmentally regulated in intestine, and Filmus et al., 1995 showed that Gpc3, which they called Oci-5, is GPI-linked heparan sulfate proteoglycan.

GENE STRUCTURE

Pilia et al. (1996) determined that the GPC3 gene contains 8 exons and encompasses approximately 500 kb.

MAPPING

By fluorescence in situ hybridization, Shen et al. (1997) mapped the GPC3 gene to human Xq26 and rat Xq36.

GENE FUNCTION

Using DNA microarrays to compare gene expression patterns in normal human placenta with those in other tissues, Sood et al. (2006) found that several genes involved in growth and tissue remodeling were expressed at relatively higher levels in the villus sections of placenta compared with other tissues. These included GPC3, CDKN1C (600856), and IGF2 (147470). The GPC3 and CDKN1C genes are mutated in patients with Simpson-Golabi-Behmel syndrome and Beckwith-Wiedemann syndrome (130650), respectively, both fetal-placental overgrowth syndromes. In contrast, loss of IGF2 is associated with fetal growth restriction in mice. The relatively higher expression of genes that both promote and suppress growth suggested to Sood et al. (2006) tight and local regulation of the pathways that control placental development. Capurro et al. (2008) found that GPC3 inhibited soluble hedgehog activity in the medium of SHH (600725)-expressing mouse embryonic fibroblasts and IHH (600726)-expressing human embryonic kidney cells. GPC3 interacted with SHH, but not with the SHH receptor Patched (PTCH1; 601309), and it competed with Patched for SHH binding. Furthermore, GPC3 induced SHH endocytosis and degradation. The heparan sulfate chains of GPC3 were not required for its interaction with SHH, but membrane attachment via the GPI anchor was required. Maurel et al. (2013) observed that expression of both microRNA-1291 (MIR1291; 615487) and GPC3 was upregulated in hepatocellular carcinoma. They found that MIR1291 did not ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 300037 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).