ADAMTS3
Chr 4ARADAM metallopeptidase with thrombospondin type 1 motif 3
Also known as: ADAMTS-4, HKLLS3
This protein cleaves propeptides of type II collagen prior to fibril assembly and does not act on types I and III collagens. Mutations cause Hennekam lymphangiectasia-lymphedema syndrome 3, which involves lymphatic abnormalities and connective tissue defects. The gene follows autosomal recessive inheritance and shows minimal constraint against loss-of-function variants (very low pLI score).
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ADAMTS3 · 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
NANOVAE to Treat Knee Osteoarthritis (KOA)
NOT YET RECRUITINGDietary Supplementation With Blueberry in OA
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools