ADAM7
Chr 8ADAM metallopeptidase domain 7
Also known as: ADAM 7, ADAM-7, EAPI, GP-83, GP83
The protein is a non-catalytic member of the ADAM family of zinc proteases that is required for normal male fertility by maintaining epithelial cell morphology in the epididymis and playing a role in sperm motility and capacitation. Mutations in this gene may be involved in melanoma progression, though no established Mendelian pediatric neurological disorders are currently associated with ADAM7 variants. The gene shows no constraint against loss-of-function variants (very low pLI score), suggesting haploinsufficiency is unlikely to cause disease.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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
227 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 | 78 | 0 | 78 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 123 | 8 | 0 | 131 |
Likely Benign | 0 | 6 | 0 | 2 | 8 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 129 | 91 | 2 | 222 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ADAM7 · 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