GPC3
Chr XXLRglypican 3
Also known as: DGSX, GTR2-2, MXR7, OCI-5, SDYS, SGB, SGBS, SGBS1
This gene encodes a cell surface proteoglycan that regulates multiple signaling pathways including hedgehog, Wnt, and BMP signaling, which are critical for embryonic development and growth control. Mutations cause Simpson-Golabi-Behmel syndrome type 1, characterized by pre- and postnatal overgrowth, distinctive facial features, and increased risk of embryonal tumors including Wilms tumor. The gene shows X-linked recessive inheritance and is highly constrained against loss-of-function mutations.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 12 | 0 | 32 | 0 | 44 |
Likely Pathogenic | 10 | 1 | 2 | 0 | 13 |
VUS | 2 | 180 | 19 | 3 | 204 |
Likely Benign | 1 | 1 | 29 | 90 | 121 |
Benign | 0 | 0 | 1 | 1 | 2 |
Conflicting | — | 3 | |||
| Total | 25 | 182 | 83 | 94 | 387 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GPC3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Phase I Study of ERY974 in Patients With Hepatocellular Carcinoma
ACTIVE NOT RECRUITINGEngineered TILs/CAR-TILs to Treat Advanced Solid Tumors
RECRUITINGGPC3-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression
RECRUITINGCytokine Armored GPC3 Specific Chimeric Antigen Receptor Expressing T-cells in Adults With Solid Tumors
NOT YET RECRUITINGInterleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
RECRUITINGInterleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells for Solid Tumors
ACTIVE NOT RECRUITINGGPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies
RECRUITINGGlypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Patients With Pediatric Solid Tumors (GAP)
ACTIVE NOT RECRUITINGInterleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
ACTIVE NOT RECRUITINGImmunotherapy for Solid Tumor Malignancies in Pediatrics Using Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor T Cells
RECRUITINGGPC-3 CAR T CELLS FOR Recurrent GPC-3 Positive Glioblastoma
RECRUITINGImmunotherapy For Adults With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells
RECRUITINGExternal Resources
Links to major genomics databases and tools