MFN2
Chr 1ADARmitofusin 2
The protein functions as a mitochondrial outer membrane protein that mediates mitochondrial fusion and maintains the mitochondrial network. Mutations cause autosomal dominant and autosomal recessive forms of Charcot-Marie-Tooth disease type 2A2 and hereditary motor and sensory neuropathy VI, both axonal peripheral neuropathies, as well as multiple symmetric lipomatosis. The high pLI score (0.99) and low LOEUF score (0.28) indicate the gene is highly intolerant to loss-of-function variants, suggesting pathogenicity occurs through haploinsufficiency or dominant-negative mechanisms.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MFN2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Evaluation of Safety and Efficiency of Metreleptin Treatment for Patients With Multiple Symmetric Lipomatosis (MSL)
ACTIVE NOT RECRUITINGMITAORTA - Role of Mitochondrial Dynamic in Aneurysm and Dissection of Ascending Thoracic Aorta
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools