ADAMTS8
Chr 11ADAM metallopeptidase with thrombospondin type 1 motif 8
Also known as: ADAM-TS8, METH2
The protein functions as a metalloproteinase with anti-angiogenic properties, disrupting blood vessel formation. Mutations in this gene have been associated with cancer predisposition, particularly lung neoplasms, following an autosomal dominant inheritance pattern. The gene shows minimal constraint against loss-of-function variants, suggesting some tolerance to protein disruption.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
253 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 | 74 | 0 | 74 |
Likely Pathogenic | 0 | 0 | 7 | 0 | 7 |
VUS | 0 | 155 | 3 | 0 | 158 |
Likely Benign | 0 | 5 | 0 | 1 | 6 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 160 | 84 | 1 | 245 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ADAMTS8 · 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