MFAP5
Chr 12ADmicrofibril associated protein 5
Also known as: AAT9, MAGP-2, MAGP2, MFAP-5, MP25
The protein is a microfibril-associated glycoprotein that serves as a component of elastin-associated microfibrils in the extracellular matrix and promotes cell attachment via alpha-V-beta-3 integrin. Mutations cause familial thoracic aortic aneurysm with autosomal dominant inheritance. The gene shows tolerance to loss-of-function variants (low constraint), suggesting the cardiovascular phenotype may involve specific functional disruption rather than simple protein loss.
Primary Disease Associations & Inheritance
Moderate evidence — consider for supplementary testing
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 loss-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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
373 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 | 1 | 0 | 35 | 0 | 36 |
Likely Pathogenic | 2 | 0 | 2 | 0 | 4 |
VUS | 16 | 111 | 29 | 2 | 158 |
Likely Benign | 0 | 4 | 59 | 46 | 109 |
Benign | 0 | 0 | 40 | 0 | 40 |
Conflicting | — | 18 | |||
| Total | 19 | 115 | 165 | 48 | 365 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MFAP5 · 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