HSPG2
Chr 1heparan sulfate proteoglycan 2
Also known as: HSPG, PLC, PRCAN, SJA, SJS, SJS1
The perlecan protein is an integral component of basement membranes that provides structural support, regulates vascular barrier function, and localizes acetylcholinesterase at neuromuscular junctions. Biallelic mutations cause Schwartz-Jampel syndrome type 1 (characterized by muscle stiffness and skeletal abnormalities) and Silverman-Handmaker type dyssegmental dysplasia (a severe skeletal dysplasia), both inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function variants, reflecting its essential role in development and tissue integrity.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
500 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 | 5 | 0 | 0 | 0 | 5 |
Likely Pathogenic | 4 | 0 | 2 | 0 | 6 |
VUS | 1 | 241 | 8 | 3 | 253 |
Likely Benign | 0 | 4 | 63 | 86 | 153 |
Benign | 0 | 0 | 3 | 0 | 3 |
| Total | 10 | 245 | 76 | 89 | 420 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HSPG2 · 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