ADAM28
Chr 8ADAM metallopeptidase domain 28
Also known as: ADAM 28, MDC-L, MDCL, eMDC II, eMDCII
The protein is a lymphocyte-expressed metalloprotease and disintegrin that mediates cell adhesion and proteolytic processing of surface proteins including FASL and CD40L, and may function in sperm maturation. ADAM28 mutations cause autosomal recessive cone-rod dystrophy, a retinal degeneration disorder affecting central vision. The gene shows low constraint to loss-of-function variation, consistent with recessive inheritance where one functional copy is insufficient.
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
244 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 | 109 | 5 | 0 | 114 |
Likely Benign | 0 | 8 | 1 | 3 | 12 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 0 | 118 | 88 | 3 | 209 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ADAM28 · 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