GPC1
Chr 2glypican 1
Also known as: glypican
The GPC1 protein is a cell surface heparan sulfate proteoglycan that binds collagen, participates in Schwann cell myelination, and regulates skeletal muscle differentiation by sequestering FGF2 signaling. Mutations cause autosomal recessive omodysplasia types 1 and 2, characterized by congenital limb malformations and facial dysmorphism. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance patterns.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
254 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 | 0 | 0 | 93 | 0 | 93 |
Likely Pathogenic | 0 | 0 | 7 | 0 | 7 |
VUS | 0 | 121 | 11 | 0 | 132 |
Likely Benign | 0 | 4 | 0 | 2 | 6 |
Benign | 0 | 0 | 0 | 2 | 2 |
| Total | 0 | 125 | 111 | 4 | 240 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GPC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
ACTIVE NOT RECRUITINGInterleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
RECRUITINGCytokine Armored GPC3 Specific Chimeric Antigen Receptor Expressing T-cells in Adults With Solid Tumors
NOT YET RECRUITINGInterleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells for 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
RECRUITINGGlypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Patients With Pediatric Solid Tumors (GAP)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools