MFN2
Mitofusin 2
Gene Summary
RefSeq / NCBIThis gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. This protein is involved in the regulation of vascular smooth muscle cell proliferation, and it may play a role in the pathophysiology of obesity. Mutations in this gene cause Charcot-Marie-Tooth disease type 2A2, and hereditary motor and sensory neuropathy VI, which are both disorders of the peripheral nervous system. Defects in this gene have also been associated with early-onset stroke. Two transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]
Clinical Phenotype
Charcot-Marie-Tooth disease type 2A (CMT2A): axonal neuropathy with early onset, predominantly motor > sensory involvement, and often severe disability. Some patients also show optic atrophy.
Molecular Mechanism
MFN2 encodes a GTPase mediating outer mitochondrial membrane fusion. Mutations impair mitochondrial fusion and axonal mitochondrial transport (particularly critical for long peripheral nerve axons). Mitochondria cluster at the cell body rather than reaching distal axon terminals.
Clinical Hallmarks & Key Evidence
CMT2A is the most common axonal CMT subtype. NCS shows reduced amplitude with normal or near-normal conduction velocities (axonal pattern).
Zuchner S et al. Nat Genet. 2004;36(5):449-51.
Pyramidal features (spasticity, hyperreflexia) coexist with peripheral neuropathy in some CMT2A patients — a clinical red flag for an axonal CMT with central involvement.
Feely SM et al. Brain. 2011;134(Pt 11):3368-79.
Optic atrophy in CMT2A (HMSN VI) reflects high dependence of retinal ganglion cells on mitochondrial transport over long axons to the lateral geniculate nucleus.
Zuchner S et al. Ann Neurol. 2006;59(3):597-601.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.