GPC3

Summary

GPC3 (glypican 3, HGNC:4451) is a protein-coding gene on chromosome Xq26.2, encoding Glypican-3 (P51654). Cell surface proteoglycan. It is haploinsufficient (ClinGen: sufficient evidence).

Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. The protein encoded by this gene can bind to and inhibit the dipeptidyl peptidase activity of CD26, and it can induce apoptosis in certain cell types. Deletion mutations in this gene are associated with Simpson-Golabi-Behmel syndrome, also known as Simpson dysmorphia syndrome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2719 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Simpson-Golabi-Behmel syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 1,136 total — 71 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 162
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004484

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4451
Approved symbol	GPC3
Name	glypican 3
Location	Xq26.2
Locus type	gene with protein product
Status	Approved
Aliases	OCI-5, SGBS, SGBS1, SGB, DGSX
Ensembl gene	ENSG00000147257
Ensembl biotype	protein_coding
OMIM	300037
Entrez	2719

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000370818, ENST00000394299, ENST00000406757, ENST00000631057, ENST00000666017, ENST00000666673, ENST00000667662, ENST00000669691, ENST00000684880, ENST00000689310, ENST00000692074, ENST00000692084, ENST00000692630, ENST00000911059, ENST00000925126, ENST00000925127

RefSeq mRNA: 4 — MANE Select: NM_004484 NM_001164617, NM_001164618, NM_001164619, NM_004484

CCDS: CCDS14638, CCDS55495, CCDS55496, CCDS94667

Canonical transcript exons

ENST00000370818 — 8 exons

Exon	Start	End
ENSE00001153991	133596440	133596599
ENSE00001153999	133661730	133661850
ENSE00001154005	133692369	133692494
ENSE00001154011	133699895	133700028
ENSE00001154018	133753482	133754176
ENSE00001636563	133953050	133953211
ENSE00001811125	133985275	133985594
ENSE00001921825	133535745	133536293

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 98.03.

FANTOM5 (CAGE): breadth broad, TPM avg 55.5101 / max 2134.5468, expressed in 737 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200570	38.2372	517
200571	6.9931	483
200573	6.8074	496
200568	3.2125	219
200572	0.1610	109
200566	0.0990	55

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
upper lobe of left lung	UBERON:0008952	98.03	gold quality
right lung	UBERON:0002167	97.79	gold quality
tibial nerve	UBERON:0001323	97.33	gold quality
upper lobe of lung	UBERON:0008948	97.13	gold quality
placenta	UBERON:0001987	96.29	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.20	gold quality
adenohypophysis	UBERON:0002196	96.12	gold quality
metanephros cortex	UBERON:0010533	95.95	gold quality
omental fat pad	UBERON:0010414	95.84	gold quality
peritoneum	UBERON:0002358	95.81	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.80	gold quality
adipose tissue	UBERON:0001013	95.70	gold quality
cartilage tissue	UBERON:0002418	94.08	gold quality
connective tissue	UBERON:0002384	94.02	gold quality
pituitary gland	UBERON:0000007	93.48	gold quality
lung	UBERON:0002048	93.24	gold quality
right coronary artery	UBERON:0001625	92.29	gold quality
lower lobe of lung	UBERON:0008949	90.77	gold quality
left coronary artery	UBERON:0001626	90.21	gold quality
adult mammalian kidney	UBERON:0000082	90.15	gold quality
periodontal ligament	UBERON:0008266	89.71	gold quality
coronary artery	UBERON:0001621	89.69	gold quality
right atrium auricular region	UBERON:0006631	89.49	gold quality
adrenal tissue	UBERON:0018303	89.37	gold quality
dorsal root ganglion	UBERON:0000044	88.70	gold quality
left lobe of thyroid gland	UBERON:0001120	88.62	gold quality
right lobe of thyroid gland	UBERON:0001119	88.29	gold quality
skin of leg	UBERON:0001511	87.95	gold quality
thoracic mammary gland	UBERON:0005200	87.87	gold quality
thyroid gland	UBERON:0002046	87.68	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	4256.61
E-HCAD-24	yes	2227.78
E-GEOD-130473	yes	2210.33
E-HCAD-10	yes	1958.60
E-MTAB-8221	yes	1940.50
E-MTAB-6701	yes	1896.00
E-HCAD-23	yes	1799.36
E-CURD-79	yes	1577.39
E-MTAB-7407	yes	1571.97
E-MTAB-10662	yes	1530.07
E-CURD-126	yes	1123.91
E-HCAD-56	yes	858.58
E-MTAB-9906	yes	735.11
E-MTAB-10018	yes	307.60
E-GEOD-93593	yes	14.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, SP1, ZHX2

miRNA regulators (miRDB)

36 targeting GPC3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-5681A	97.99	67.17	1658

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Candidate lung tumor suppressor gene which may be regulated by tobacco exposure. (PMID:11893651)
• Mutations in GPC3 is associated with Wilm’s tumor (PMID:12085187)
• GPC3 is upregulated in hepatocellular carcinoma and has a role in liver carcinogenesis (PMID:12478660)
• These findings suggest that GPC3 is a candidate lung tumor suppressor gene whose expression may be regulated by exposure to cigarette smoke and functions to modulate cellular response to exogenous damage. (PMID:12816733)
• Overexpressed in human hepatocellular carcinoma, hence a good molecular marker. (PMID:12824919)
• involvement in the cellular protection against mitoxantrone in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV (PMID:14661052)
• Although promoter methylation is likely to affect expression status of the GPC3 gene, study results suggest that deregulation of GPC3 transcriptional expression seen in neuroblastoma and Wilm’s tumor involves other regulatory levels. (PMID:15083193)
• GPC3 is apparently a novel tumor marker useful for the diagnosis of melanoma, especially in early stages of the disorder. (PMID:15475451)
• glypican-3-induced stimulation of hepatocellular carcinoma growth does not require convertase processing (PMID:16227623)
• GPC3 and SPARC in combination diagnosed 47 of 75 (66.2%) melanoma patients at an early stage (0-II). (PMID:16299239)
• GPC3 peptides may be applicable to cancer immunotherapy for a large number of hepatocellular carcinoma patients (PMID:16675560)
• Data show that forced expression of glypican-3 (GPC3) reduced the growth of hepatocellular carcinoma cells, and that FGF2-mediated cell proliferation was inhibited by GPC3. (PMID:16682817)
• Molecular data based on gene transcriptional profiles of a 3-gene set (GPC3, LYVE1, and survivin) allow a reliable diagnosis of early hepatocellular carcinoma. (PMID:17087938)
• Both the glycosylated and unglycosylated forms of GPC3 interact with CD26 peptidase, resulting in inhibition of the enzyme. (PMID:17549790)
• Data show that GPC3 is observed in a significant fraction of primary and corresponding recurrent ovarian carcinomas. (PMID:17581422)
• No hot spot for GPC3 mutations or deletions in the patients with Simpson-Golabi-Behmel syndrome. (PMID:17603795)
• GPC is detected by immunostaining in necroinflammatory lesions, therefore its use as a cancer stain should be interpreted cautiously. (PMID:17949778)
• GPC3 may play a role in the tumorigenesis of hepatoblastoma. (PMID:17949790)
• staining for glypican-3 is a highly sensitive and specific method capable of distinguishing HCC from other benign and malignant hepatic lesions (PMID:18264086)
• GPC3 seems to be a promising diagnostic marker for differentiating yolk sac tumors from ovarian clear cell carcinomas. (PMID:18277882)
• GPC3 confers oncogenecity through the interaction between IGF-II and its receptor, and the subsequent activation of the IGF-signaling pathway. (PMID:18413366)
• Glypican-3 appears to be a reliable markers for ovarian germ-cell tumors. (PMID:18462363)
• Glypican-3 expression is a potential candidate marker for early detection of lung squamous cell carcinoma. (PMID:18469798)
• GPC3 is expressed at an early stage, suggesting that GPC3 expression in thyroid cancer is an early event in developing papillary carcinoma. (PMID:18511877)
• Report expression pattern of glypican-3 (GPC3) during human embryonic and fetal development. (PMID:18785116)
• GPC3 is frequently expressed in noncutaneous small cell neuroendocrine carcinoma of various origins, in particular in Merkel cell carcinoma, which, in combination with CK20 (PMID:18813128)
• The effector cells stimulated with DCs that were transfected with pEF-hGPC3 plasmid could effectively lyse GPC3 expressing HepG2 cells. (PMID:18813403)
• GPC3 expression in HCCs did not correlate with the size, differentiation, or stage of the tumors; the presence or absence of cirrhotic background; or the underlying etiologies (PMID:18976006)
• Report the expression profile of glypican-3 and its relation to macrophage population in human hepatocellular carcinoma. (PMID:19141032)
• 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. (PMID:19215053)
• A reliable marker for the detection of hepatocellular carcinoma in liver biopsies. (PMID:19231003)
• overexpression of glypican-3 may be related to the development and aggressive behavior of ovarian clear cell adenocarcinoma. (PMID:19329941)
• Our data supports the potentially significant diagnostic utility of GPC-3 in fine-needle aspiration biopsies in differentiating primary malignant from benign and preneoplastic liver lesions, and metastatic carcinomas. (PMID:19405109)
• GPC3 expression is correlated with poor prognosis in hepatocellular carcinoma. (PMID:19496787)
• Detection of glypican-3-specific CTLs in chronic hepatitis and liver cirrhosis. (PMID:19513517)
• SALL4 is a more sensitive marker than PLAP, AFP, or glypican-3 for extragonadal yolk sac tumors. (PMID:19574883)
• Serum GPC3 is highly specific for detecting hepatocellular carcinoma (HCC). The combined use of serum GPC3 and alpha-fetoprotein may better differentiate HCC from benign liver disorders, as well as from other liver cancers. (PMID:19793164)
• Data show that mutated GPC3 lacking the GPI anchoring domain (sGPC3) significantly inhibited the in vivo growth, blocked Wnt signaling and Erk1/2 and Akt phosphorylation in tumors. (PMID:19816934)
• glypican-3 is involved in the recruitment of M2-polarized tumor-associated macrophages in hepatocellular carcinoma (PMID:19838081)
• YST can display a variety of growth patterns that can be confused with other germ cell tumour components. GPC3 detects all growth patterns tested and has a higher sensitivity for detecting YST (PMID:20546340)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpc3	ENSDARG00000032199
mus_musculus	Gpc3	ENSMUSG00000055653
rattus_norvegicus	Gpc3	ENSRNOG00000060179
drosophila_melanogaster	dally	FBGN0263930
caenorhabditis_elegans		WBGENE00001687

Paralogs (5): GPC1 (ENSG00000063660), GPC4 (ENSG00000076716), GPC5 (ENSG00000179399), GPC6 (ENSG00000183098), GPC2 (ENSG00000213420)

Protein

Protein identifiers

Glypican-3 — P51654 (reviewed: P51654)

Alternative names: GTR2-2, Intestinal protein OCI-5, MXR7

All UniProt accessions (6): P51654, A0A8I5KUG1, A0A8I5KYY0, B4DTD8, H0Y3U6, I6QTG3

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface proteoglycan. Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for binding to hedgehog proteins. Binding to the hedgehog protein SHH triggers internalization of the complex by endocytosis and its subsequent lysosomal degradation. Positively regulates the canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled and stimulating the binding of the Frizzled receptor to Wnt ligands. Positively regulates the non-canonical Wnt signaling pathway. Binds to CD81 which decreases the availability of free CD81 for binding to the transcriptional repressor HHEX, resulting in nuclear translocation of HHEX and transcriptional repression. Inhibits the dipeptidyl peptidase activity of DPP4. Plays a role in limb patterning and skeletal development by controlling the cellular response to BMP4. Modulates the effects of growth factors BMP2, BMP7 and FGF7 on renal branching morphogenesis. Required for coronary vascular development. Plays a role in regulating cell movements during gastrulation.

Subunit / interactions. Heterodimer; disulfide-linked. Cleavage by a furin-like convertase results in production of alpha and beta chains which form a disulfide-linked heterodimer. Interacts with DPP4. Interacts with FGF2. Interacts with WNT5A. Also interacts with WNT3A and WNT7B. Interacts with hedgehog protein SHH; the heparan sulfate chains are not required for the interaction. Also interacts with hedgehog protein IHH. Interacts with CD81. Interacts with Wnt receptors FZD4, FZD7 and FZD8; the heparan sulfate chains are required for the interaction.

Subcellular location. Cell membrane.

Tissue specificity. Detected in placenta (at protein level). Highly expressed in lung, liver and kidney.

Post-translational modifications. O-glycosylated; contains heparan sulfate and/or chondroitin sulfate. Cleaved intracellularly by a furin-like convertase to generate 2 subunits, alpha and beta, which remain associated through disulfide bonds and are associated with the cell surface via the GPI-anchor. This processing is essential for its role in inhibition of hedgehog signaling. A second proteolytic event may result in cleavage of the protein on the cell surface, separating it from the GPI-anchor and leading to its shedding from the cell surface.

Disease relevance. Simpson-Golabi-Behmel syndrome 1 (SGBS1) [MIM:312870] A condition characterized by pre- and postnatal overgrowth (gigantism), facial dysmorphism and a variety of inconstant visceral and skeletal malformations. Characteristic dysmorphic features include macrocephaly with coarse, distinctive facies with a large protruding jaw, broad nasal bridge and cleft palate. Cardiac defects are frequent. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Used as a marker for hepatocellular carcinoma (HCC) as it is expressed in HCC but is not detectable in hepatocytes from normal or benign liver diseases. When attached to the cell surface, stimulates the growth of HCC cells by increasing canonical Wnt signaling. Cleavage is not required for stimulation of Wnt signaling or HCC growth.

Similarity. Belongs to the glypican family.

Isoforms (3)

UniProt ID	Names	Canonical?
P51654-1	1	yes
P51654-2	2, Variant B
P51654-3	3, Variant C

RefSeq proteins (4): NP_001158089, NP_001158090, NP_001158091, NP_004475* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001863	Glypican	Family
IPR019803	Glypican_CS	Conserved_site

Pfam: PF01153

UniProt features (52 total): helix 17, disulfide bond 7, mutagenesis site 6, glycosylation site 5, strand 3, chain 2, splice variant 2, sequence variant 2, turn 2, modified residue 2, signal peptide 1, propeptide 1, site 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7ZAW	X-RAY DIFFRACTION	2.58
9NTQ	ELECTRON MICROSCOPY	4.04
7ZA1	X-RAY DIFFRACTION	4.1
9NTT	ELECTRON MICROSCOPY	7.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51654-F1	75.60	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 358–359 (cleavage)

Post-translational modifications (3): 25, 352, 554

Disulfide bonds (7): 35–72, 65–262, 73–265, 197–349, 252–285, 274–422, 278–410

Glycosylation sites (5): 418, 495, 509, 124, 241

Mutagenesis-validated functional residues (6):

Position	Phenotype
355–358	abolishes proteolytic processing. abolishes interaction with wnt5a and ability to regulate wnt signaling. increases bind
355	no effect on proteolytic processing.
358	no effect on proteolytic processing.
371–374	no effect on proteolytic processing.
387–389	no effect on proteolytic processing.
394–396	no effect on proteolytic processing.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-2022928	HS-GAG biosynthesis
R-HSA-2024096	HS-GAG degradation
R-HSA-3560783	Defective B4GALT7 causes EDS, progeroid type
R-HSA-3560801	Defective B3GAT3 causes JDSSDHD
R-HSA-3656237	Defective EXT2 causes exostoses 2
R-HSA-3656253	Defective EXT1 causes exostoses 1, TRPS2 and CHDS
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-9694614	Attachment and Entry
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry
R-HSA-9833110	RSV-host interactions
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 758 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, LI_CISPLATIN_RESISTANCE_DN, MODULE_52, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_BODY_MORPHOGENESIS, BENPORATH_ES_WITH_H3K27ME3, GOBP_AXIS_SPECIFICATION, GRUETZMANN_PANCREATIC_CANCER_DN

GO Biological Process (39): branching involved in ureteric bud morphogenesis (GO:0001658), smoothened signaling pathway (GO:0007224), response to bacterium (GO:0009617), anatomical structure morphogenesis (GO:0009653), anterior/posterior axis specification (GO:0009948), body morphogenesis (GO:0010171), cell migration (GO:0016477), bone mineralization (GO:0030282), osteoclast differentiation (GO:0030316), lung development (GO:0030324), positive regulation of BMP signaling pathway (GO:0030513), embryonic hindlimb morphogenesis (GO:0035116), cell migration involved in gastrulation (GO:0042074), positive regulation of protein catabolic process (GO:0045732), positive regulation of endocytosis (GO:0045807), negative regulation of smoothened signaling pathway (GO:0045879), positive regulation of smoothened signaling pathway (GO:0045880), negative regulation of growth (GO:0045926), positive regulation of D-glucose import across plasma membrane (GO:0046326), epithelial cell proliferation (GO:0050673), negative regulation of epithelial cell proliferation (GO:0050680), canonical Wnt signaling pathway (GO:0060070), Wnt signaling pathway, planar cell polarity pathway (GO:0060071), regulation of canonical Wnt signaling pathway (GO:0060828), coronary vasculature development (GO:0060976), cell proliferation involved in kidney development (GO:0072111), mesenchymal cell proliferation involved in ureteric bud development (GO:0072138), mesonephric duct morphogenesis (GO:0072180), cell proliferation involved in metanephros development (GO:0072203), negative regulation of canonical Wnt signaling pathway (GO:0090090), positive regulation of canonical Wnt signaling pathway (GO:0090263), regulation of protein localization to membrane (GO:1905475), regulation of non-canonical Wnt signaling pathway (GO:2000050), positive regulation of Wnt signaling pathway, planar cell polarity pathway (GO:2000096), kidney development (GO:0001822), negative regulation of cell population proliferation (GO:0008285), animal organ morphogenesis (GO:0009887), regulation of signal transduction (GO:0009966), regulation of growth (GO:0040008)

GO Molecular Function (3): peptidyl-dipeptidase inhibitor activity (GO:0060422), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (9): endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), cell surface (GO:0009986), lysosomal lumen (GO:0043202), side of membrane (GO:0098552), lysosome (GO:0005764), membrane (GO:0016020), obsolete collagen-containing extracellular matrix (GO:0062023)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	5
Heparan sulfate/heparin (HS-GAG) metabolism	2
Coagulation pathway	2
Respiratory Syncytial Virus Infection Pathway	2
Dengue Virus Infection	2
Glycosaminoglycan metabolism	1
Metabolism of proteins	1
Post-translational protein modification	1
Early SARS-CoV-2 Infection Events	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
smoothened signaling pathway	2
regulation of smoothened signaling pathway	2
intracellular organelle lumen	2
membrane	2
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
cell surface receptor signaling pathway	1
response to other organism	1
developmental process	1
anatomical structure development	1
axis specification	1
anterior/posterior pattern specification	1
anatomical structure morphogenesis	1
cell motility	1
ossification	1
biomineral tissue development	1
myeloid leukocyte differentiation	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
embryonic limb morphogenesis	1
hindlimb morphogenesis	1
ameboidal-type cell migration	1
gastrulation	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
endocytosis	1
regulation of endocytosis	1
positive regulation of transport	1
positive regulation of cellular component organization	1
negative regulation of signal transduction	1
positive regulation of signal transduction	1
growth	1
regulation of growth	1

Protein interactions and networks

STRING

2264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPC3	IGF2	P01344	928
GPC3	CD81	P18582	887
GPC3	AFP	P02771	871
GPC3	WNT3A	P56704	859
GPC3	IGF1R	P08069	797
GPC3	KRT19	P08727	775
GPC3	EPCAM	P16422	738
GPC3	SULF2	Q8IWU5	738
GPC3	GOLM1	Q8NBJ4	736
GPC3	PTCH1	Q13635	727
GPC3	GPC2	Q8N158	716
GPC3	SALL4	Q9UJQ4	705
GPC3	TFPI	P10646	679
GPC3	DPP4	P27487	679
GPC3	KRT7	P08729	664

IntAct

66 interactions, top by confidence:

A	B	Type	Score
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
MOXD1	GPAA1	psi-mi:“MI:0914”(association)	0.620
AFP	GPC3	psi-mi:“MI:0407”(direct interaction)	0.590
AFP	GPC3	psi-mi:“MI:0915”(physical association)	0.590
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
ULBP1	IGLL5	psi-mi:“MI:0914”(association)	0.530
GPR183	NRP1	psi-mi:“MI:0914”(association)	0.530
LIPG	NRP1	psi-mi:“MI:0914”(association)	0.530
LMAN2	PLXNB2	psi-mi:“MI:0914”(association)	0.530
FGF1	SDC4	psi-mi:“MI:0914”(association)	0.530
TSPYL1	GPC3	psi-mi:“MI:0914”(association)	0.530
PDPK1	AGRN	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
HADHA	AGRN	psi-mi:“MI:0914”(association)	0.530
GPC3	CLGN	psi-mi:“MI:0914”(association)	0.530
LRRTM2	GPC3	psi-mi:“MI:0914”(association)	0.530
DAXX	TNRC18	psi-mi:“MI:0914”(association)	0.530
HADHA	GPC4	psi-mi:“MI:0914”(association)	0.530
LRRTM3	SGPL1	psi-mi:“MI:0914”(association)	0.530
GPC3	CANX	psi-mi:“MI:0914”(association)	0.530
APP	GPC3	psi-mi:“MI:0407”(direct interaction)	0.440
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (89): GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS)

ESM2 similar proteins: A1L3I3, A2AWH2, A2BDP1, A4IFM1, A4IHZ3, A5A6P7, A7E2V4, B1AL88, F1N4E5, O14525, O35181, O75949, O94901, O94983, P13265, P51654, P56975, P78333, Q07105, Q0VCT2, Q29016, Q2F7Z7, Q3T0Q2, Q3V140, Q4FZU8, Q4R8C8, Q5HZE8, Q5PQX1, Q5R7A3, Q5R800, Q60485, Q61137, Q68FE6, Q6H9L7, Q6P7B4, Q6V9Y8, Q6ZS17, Q7TNI2, Q80Y50, Q8BHP7

Diamond homologs: A5A6P7, P13265, P51654, P78333, Q6V9Y8, Q8CAL5, Q8CFZ4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GPC3	down-regulates	DPP4	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Attachment and Entry	5	50.9×	1e-05
Retinoid metabolism and transport	5	21.0×	2e-04
Regulation of clotting cascade	5	19.8×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1136 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	71
Likely pathogenic	26
Uncertain significance	489
Likely benign	342
Benign	42

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027392	NM_004484.4(GPC3):c.175+1G>T	Pathogenic
1067035	NM_004484.4(GPC3):c.1569del (p.Ala524fs)	Pathogenic
1069346	NC_000023.10:g.(?132670152)(133119476_?)del	Pathogenic
1069347	NC_000023.10:g.(?132670146)(132670327_?)del	Pathogenic
1069348	NC_000023.10:g.(?132795752)(132888209_?)del	Pathogenic
1074502	NM_004484.4(GPC3):c.892G>T (p.Glu298Ter)	Pathogenic
11685	NM_004484.4(GPC3):c.194_206del (p.Cys65fs)	Pathogenic
11686	NC_000023.11:g.133596443_133596602del	Pathogenic
11687	NM_004484.4(GPC3):c.886T>A (p.Trp296Arg)	Pathogenic
11688	NM_004484.4(GPC3):c.1292+1G>T	Pathogenic
11689	NM_004484.4(GPC3):c.595C>T (p.Arg199Ter)	Pathogenic
11690	NM_004484.4(GPC3):c.361C>T (p.His121Tyr)	Pathogenic
11692	NC_000023.11:g.(133661675_133661730)_(133661850_133661926)del	Pathogenic
11693	NM_004484.4(GPC3):c.337+1G>A	Pathogenic
11694	NM_004484.4(GPC3):c.1159C>T (p.Arg387Ter)	Pathogenic
1433596	NM_004484.4(GPC3):c.885C>A (p.Tyr295Ter)	Pathogenic
1453391	NM_004484.4(GPC3):c.1379_1382del (p.Ser460fs)	Pathogenic
1455474	NM_004484.4(GPC3):c.175+2T>C	Pathogenic
1455674	NM_004484.4(GPC3):c.662del (p.Lys221fs)	Pathogenic
1458423	NC_000023.10:g.(?132670152)(132888213_?)del	Pathogenic
1460460	NC_000023.10:g.(?132670132)(133119496_?)del	Pathogenic
146866	GRCh38/hg38 Xq26.2(chrX:133687309-134090471)x0	Pathogenic
1686763	NM_004484.4(GPC3):c.760C>T (p.Arg254Ter)	Pathogenic
1703564	GRCh37/hg19 Xq26.2(chrX:132703748-132794615)	Pathogenic
1707556	NM_004484.4(GPC3):c.280del (p.Gln94fs)	Pathogenic
1712296	NC_000023.10:g.(133030929_133031380)(133079087_133079463)delins(118528009_118528409)(118674690_118675082)	Pathogenic
1808618	GRCh37/hg19 Xq26.2(chrX:132879202-132956033)x0	Pathogenic
1902190	NM_004484.4(GPC3):c.1300C>T (p.Gln434Ter)	Pathogenic
2025427	NM_004484.4(GPC3):c.607del (p.Arg203fs)	Pathogenic
2027561	NM_004484.4(GPC3):c.1268G>A (p.Trp423Ter)	Pathogenic

SpliceAI

3256 predictions. Top by Δscore:

Variant	Effect	Δscore
X:133536289:CAGTT:C	acceptor_gain	1.0000
X:133536290:AGTTC:A	acceptor_loss	1.0000
X:133536291:GTT:G	acceptor_gain	1.0000
X:133536292:TT:T	acceptor_gain	1.0000
X:133536293:TC:T	acceptor_loss	1.0000
X:133536294:C:CC	acceptor_gain	1.0000
X:133536294:CT:C	acceptor_loss	1.0000
X:133536295:T:C	acceptor_loss	1.0000
X:133596435:GTTAC:G	donor_loss	1.0000
X:133596436:TTACC:T	donor_loss	1.0000
X:133596437:TA:T	donor_loss	1.0000
X:133596438:ACCTG:A	donor_loss	1.0000
X:133596439:C:CG	donor_loss	1.0000
X:133596595:AGGAG:A	acceptor_gain	1.0000
X:133596600:C:CC	acceptor_gain	1.0000
X:133661726:ATAC:A	donor_loss	1.0000
X:133661728:A:AT	donor_loss	1.0000
X:133661851:C:CC	acceptor_gain	1.0000
X:133699890:CTCAC:C	donor_loss	1.0000
X:133699892:CA:C	donor_loss	1.0000
X:133699893:A:AC	donor_gain	1.0000
X:133699893:ACCT:A	donor_loss	1.0000
X:133699894:C:CC	donor_gain	1.0000
X:133699894:CCTT:C	donor_gain	1.0000
X:133700024:CCAAT:C	acceptor_gain	1.0000
X:133700025:CAAT:C	acceptor_gain	1.0000
X:133700025:CAATC:C	acceptor_gain	1.0000
X:133700026:AAT:A	acceptor_gain	1.0000
X:133700027:AT:A	acceptor_gain	1.0000
X:133700027:ATCTG:A	acceptor_loss	1.0000

AlphaMissense

3867 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:133661746:A:G	L466P	1.000
X:133692392:C:A	W423C	1.000
X:133692392:C:G	W423C	1.000
X:133692396:C:G	C422S	1.000
X:133692397:A:T	C422S	1.000
X:133753693:C:T	C274Y	1.000
X:133753728:G:C	C262W	1.000
X:133753729:C:T	C262Y	1.000
X:133753808:C:G	G236R	1.000
X:133753808:C:T	G236R	1.000
X:133753820:C:G	A232P	1.000
X:133754150:C:G	A122P	1.000
X:133953193:C:G	C65S	1.000
X:133953194:A:G	C65R	1.000
X:133953194:A:T	C65S	1.000
X:133661748:T:A	K465N	0.999
X:133661748:T:G	K465N	0.999
X:133661749:T:A	K465I	0.999
X:133692394:A:G	W423R	0.999
X:133692394:A:T	W423R	0.999
X:133692395:G:C	C422W	0.999
X:133692396:C:T	C422Y	0.999
X:133692397:A:G	C422R	0.999
X:133700015:C:G	C349S	0.999
X:133700016:A:T	C349S	0.999
X:133753626:C:A	W296C	0.999
X:133753626:C:G	W296C	0.999
X:133753628:A:G	W296R	0.999
X:133753628:A:T	W296R	0.999
X:133753661:A:G	C285R	0.999

dbSNP variants (sampled 300 via entrez): RS1000018047 (X:133697300 A>T), RS1000051467 (X:133982441 A>T), RS1000059655 (X:133596296 G>A,T), RS1000060298 (X:133673680 T>G), RS1000065866 (X:133762982 C>T), RS1000069257 (X:133569028 C>T), RS1000072912 (X:133983257 T>C), RS1000075027 (X:133882423 T>C), RS1000078758 (X:133667341 A>C), RS1000078963 (X:133707996 G>A), RS1000107255 (X:133775662 T>C), RS1000110411 (X:133847509 A>C), RS1000137621 (X:133687938 A>G), RS1000146596 (X:133557330 A>T), RS1000147452 (X:133806945 G>A)

Disease associations

OMIM: gene MIM:300037 | disease phenotypes: MIM:194070, MIM:312870, MIM:167000

GenCC curated gene-disease

Disease	Classification	Inheritance
Simpson-Golabi-Behmel syndrome type 1	Definitive	X-linked
Simpson-Golabi-Behmel syndrome	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Simpson-Golabi-Behmel syndrome	Definitive	XL

Mondo (7): Wilms tumor 1 (MONDO:0008679), Simpson-Golabi-Behmel syndrome type 1 (MONDO:0020602), hereditary neoplastic syndrome (MONDO:0015356), intellectual disability (MONDO:0001071), hereditary ataxia (MONDO:0100309), ovarian cancer (MONDO:0008170), Simpson-Golabi-Behmel syndrome (MONDO:0010731)

Orphanet (6): Simpson-Golabi-Behmel syndrome (Orphanet:373), Nephroblastoma (Orphanet:654), Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary ataxia (Orphanet:183518), Rare ovarian cancer (Orphanet:213500), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

162 total (30 of 162 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000072	Hydroureter
HP:0000073	Ureteral duplication
HP:0000085	Horseshoe kidney
HP:0000086	Ectopic kidney
HP:0000098	Tall stature
HP:0000105	Enlarged kidney
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000189	Narrow palate
HP:0000204	Cleft upper lip
HP:0000212	Gingival overgrowth
HP:0000238	Hydrocephalus
HP:0000243	Trigonocephaly
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000297	Facial hypotonia
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002185_1	Relative hand skill	2.000000e-06
GCST006442_456	Educational attainment (years of education)	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009902	handedness
EFO:0004784	self reported educational attainment

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
C531684	Hereditary spinal ataxia (supp.)
C537340	Simpson-Golabi-Behmel syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630889 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Tumour-associated antigens

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.52	Kd	300	nM	CHEMBL5562632
6.52	Kd	300	nM	CHEMBL5569971
6.52	Kd	300	nM	CHEMBL5568879
6.42	Kd	380	nM	CHEMBL5571913

PubChem BioAssay actives

4 with measured affinity, of 5 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[(2S)-4-carboxy-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[(2S)-2-[[(2S)-3-carboxy-2-[4-[[(17S,18S)-18-(2-carboxyethyl)-20-(carboxymethyl)-12-ethenyl-7-ethyl-3,8,13,17-tetramethyl-17,18,21,23-tetrahydroporphyrin-2-carbonyl]amino]butanoylamino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]butanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]butanoyl]amino]-4-methylpentanoic acid	2097447: Binding affinity to GPC3 (unknown origin) assessed as dissociation constant by fluorescence polarization assay	kd	0.3000	uM
(2S)-5-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[4-[[(17S,18S)-18-(2-carboxyethyl)-20-(carboxymethyl)-12-ethenyl-7-ethyl-3,8,13,17-tetramethyl-17,18,21,23-tetrahydroporphyrin-2-carbonyl]amino]butanoylamino]pentanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]acetyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoic acid	2097447: Binding affinity to GPC3 (unknown origin) assessed as dissociation constant by fluorescence polarization assay	kd	0.3000	uM
(2S)-5-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[4-[[(17S,18S)-18-(2-carboxyethyl)-20-(carboxymethyl)-12-ethenyl-7-ethyl-3,8,13,17-tetramethyl-17,18,21,23-tetrahydroporphyrin-2-carbonyl]amino]butanoylamino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]acetyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoic acid	2097447: Binding affinity to GPC3 (unknown origin) assessed as dissociation constant by fluorescence polarization assay	kd	0.3000	uM
(2S)-2-[[(2S)-4-carboxy-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-carboxy-2-[4-[[(17S,18S)-18-(2-carboxyethyl)-20-(carboxymethyl)-12-ethenyl-7-ethyl-3,8,13,17-tetramethyl-17,18,21,23-tetrahydroporphyrin-2-carbonyl]amino]butanoylamino]propanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]butanoyl]amino]-4-methylpentanoic acid	2097447: Binding affinity to GPC3 (unknown origin) assessed as dissociation constant by fluorescence polarization assay	kd	0.3800	uM

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression, increases methylation	7
bisphenol A	affects expression, affects cotreatment, increases methylation, increases expression	3
trichostatin A	affects cotreatment, decreases expression	3
entinostat	increases expression, affects cotreatment, decreases expression	2
monomethylarsonous acid	affects expression, increases expression	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects cotreatment, decreases expression, decreases methylation	2
beta-Naphthoflavone	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	decreases expression	1
deoxynivalenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Antineoplastic Agents, Immunological	affects binding	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Gemcitabine	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5539205	Binding	Binding affinity to GPC3 (unknown origin) assessed as dissociation constant by fluorescence polarization assay	Smart glypican-3-targeting peptide-chlorin e6 conjugates for targeted photodynamic therapy of hepatocellular carcinoma. — Eur J Med Chem

Cellosaurus cell lines

8 cell lines: 3 transformed cell line, 3 cancer cell line, 1 spontaneously immortalized cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7BH	Abeomics CHO-K1 GPC3	Spontaneously immortalized cell line	Female
CVCL_D7C1	Abeomics HEK293 GPC3	Transformed cell line	Female
CVCL_D8LZ	Ubigene HCT 116 GPC3 KO	Cancer cell line	Male
CVCL_E6U0	Genomeditech HEK-293 H_GPC3	Transformed cell line	Female
CVCL_F0T3	Hep-G2 GPC3 KO	Cancer cell line	Male
CVCL_SQ36	HAP1 GPC3 (-)	Cancer cell line	Male
CVCL_UE41	293T human GPC3	Transformed cell line	Female
CVCL_Y605	GM13034	Finite cell line	Male

Clinical trials (associated diseases)

265 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
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