PRG4
Chr 1ARproteoglycan 4
Also known as: CACP, HAPO, JCAP, MSF, SZP
This gene encodes a large proteoglycan that functions as a boundary lubricant at the cartilage surface and contributes to the elastic absorption and energy dissipation of synovial fluid. Mutations cause camptodactyly-arthropathy-coxa vara-pericarditis syndrome, a multisystem disorder affecting joints, bones, and the pericardium. This condition follows autosomal recessive inheritance.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
364 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 | 28 | 1 | 25 | 0 | 54 |
Likely Pathogenic | 14 | 0 | 0 | 0 | 14 |
VUS | 0 | 214 | 6 | 0 | 220 |
Likely Benign | 0 | 24 | 2 | 28 | 54 |
Benign | 0 | 7 | 2 | 3 | 12 |
Conflicting | — | 1 | |||
| Total | 42 | 246 | 35 | 31 | 355 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PRG4 · 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
External Resources
Links to major genomics databases and tools