MFN2

Chr 1ADAR

mitofusin 2

Also known as: CMT2A, CMT2A2, CMT2A2A, CMT2A2B, CPRP1, HMSN6A, HSG, MARF

NCBI Gene: 9927 ENSG00000116688 UniProt: O95140 OMIM: 608507

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This 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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, axonal, type 2A2AMIM #609260

Charcot-Marie-Tooth disease, axonal, type 2A2BMIM #617087

Hereditary motor and sensory neuropathy VIAMIM #601152

Lipomatosis, multiple symmetric, with or without peripheral neuropathyMIM #151800

UniProtNeuropathy, hereditary motor and sensory, 6A, with optic atrophy

Clinical highlights

Gene-disease validity (ClinGen)

multiple symmetric lipomatosis with partial lipodystrophy · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

642

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.28

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

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