ADAMTSL1
Chr 9ADAMTS like 1
Also known as: ADAMTSL-1, ADAMTSR1, C9orf94, PUNCTIN
The protein is a secreted extracellular matrix component that contains thrombospondin motifs but lacks the metalloproteinase domains typical of other ADAMTS family members. Mutations cause geleophysic dysplasia, a rare skeletal dysplasia characterized by short stature, joint contractures, distinctive facial features, and cardiac valve abnormalities, with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.531), indicating that complete loss of protein function is likely deleterious.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
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
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 | 0 | 0 | 84 | 0 | 84 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 2 | 323 | 12 | 0 | 337 |
Likely Benign | 0 | 17 | 9 | 9 | 35 |
Benign | 0 | 0 | 0 | 7 | 7 |
Conflicting | — | 1 | |||
| Total | 2 | 340 | 110 | 16 | 469 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ADAMTSL1 · 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