GPC5
Chr 13glypican 5
GPC5 encodes a cell surface proteoglycan that bears heparan sulfate and is anchored to the membrane via a glycosyl phosphatidylinositol linkage. Mutations cause Simpson-Golabi-Behmel syndrome type 2, an X-linked overgrowth disorder characterized by pre- and postnatal overgrowth, intellectual disability, and distinctive facial features. The gene shows extreme intolerance to loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
236 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 | 80 | 0 | 80 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 94 | 24 | 0 | 118 |
Likely Benign | 0 | 7 | 12 | 1 | 20 |
Benign | 0 | 1 | 2 | 2 | 5 |
Conflicting | — | 2 | |||
| Total | 0 | 102 | 121 | 3 | 228 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GPC5 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools