A2ML1
Chr 12ADalpha-2-macroglobulin like 1
Also known as: CPAMD9, OMS, p170
The A2ML1 protein functions as a broad-spectrum protease inhibitor that traps proteases through a unique bait-and-capture mechanism involving conformational changes and covalent binding. Autosomal dominant mutations cause increased susceptibility to otitis media, though the gene has also been reported in some cases of Noonan syndrome. This gene shows minimal constraint against loss-of-function variants based on population genetics data.
Primary Disease Associations & Inheritance
Disputed — evidence questions this relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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 | 3 | 0 | 3 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 27 | 249 | 26 | 3 | 305 |
Likely Benign | 0 | 5 | 72 | 89 | 166 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 2 | |||
| Total | 27 | 254 | 103 | 92 | 478 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
A2ML1 · 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