ADAMTS15
Chr 11ARADAM metallopeptidase with thrombospondin type 1 motif 15
Also known as: DA12
The ADAMTS15 protein is a metalloprotease that cleaves the proteoglycan versican in the pericellular matrix surrounding myoblasts, facilitating myoblast contact and fusion required for skeletal muscle development and regeneration. Mutations cause distal arthrogryposis type 12, a condition affecting joint mobility primarily in the hands and feet, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (pLI near 1.0), indicating intolerance to protein-truncating mutations.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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.
ClinVar Variant Classifications
100 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 | 1 | 1 | 16 | 0 | 18 |
Likely Pathogenic | 0 | 1 | 4 | 0 | 5 |
VUS | 0 | 68 | 1 | 0 | 69 |
Likely Benign | 0 | 3 | 0 | 1 | 4 |
Benign | 0 | 1 | 0 | 3 | 4 |
| Total | 1 | 74 | 21 | 4 | 100 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ADAMTS15 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools