Gene Function

Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion. Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events. Overexpression induces the formation of mitochondrial networks. Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (Probable). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes (By similarity). Plays an important role in the regulation of vascular smooth muscle cell proliferation (By similarity). Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy). Is required for PRKN recruitment to dysfunctional mitochondria. Involved in the control of unfolded protein response (UPR) upon ER stress including activation of apoptosis and autophagy during ER stress (By similarity). Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions (By similarity) Source: UniProt

Relationship to CMT

CMT2HMSN AD, AR
4 subtypes
1p36.22

First described 2004
Mitochondrial involvement

Subtype	Inheritance	Class	OMIM	Sentinel Publication
SubtypeCMT2A	Inheritanceautosomal dominant	ClassCMT2	OMIM609260	Sentinel Publication Mutations in the Mitochondrial GTPase Mitofusin 2 Cause Charcot-Marie-Tooth Neuropathy Type 2A 2004 · 10.1038/ng1341 Charcot-Marie-Tooth Disease Type 2A Caused by Mutation in a Microtubule Motor KIF1Bβ 2001 · 10.1016/s0092-8674(01)00363-4
SubtypeHMSN-6A	Inheritanceautosomal dominant	ClassHMSN	OMIM601152	Sentinel Publication Axonal Neuropathy with Optic Atrophy is Caused by Mutations in Mitofusin 2. 2006 · 10.1002/ana.20797
SubtypeCMT2B4	Inheritanceautosomal recessive	ClassCMT2	OMIMNo Entry	Sentinel Publication Severe Early-Onset Axonal Neuropathy with Homozygous and Compound Heterozygous MFN2 Mutations 2008 · 10.1212/01.wnl.0000311275.89032.22
SubtypeCMT2A2B	Inheritanceautosomal recessive	ClassCMT2	OMIM617097	Sentinel Publication Recessive Axonal Charcot-Marie-Tooth Disease Due to Compound Heterozygous Mitofusin 2 Mutations 2011 · 10.1212/WNL.0b013e3182242d4d

Stored Identifiers

HGNC Aliases: CPRP1, KIAA0214, MARF

hgnc_idHGNC:16877

ensembl_gene_idENSG00000116688

coords_grch38chr1:11980181-12015211

coords_grch37chr1:12040238-12073571

entrez_id9927

omim_gene608507

uniprot_idsO95140

refseq_accessionNM_014874

mane_refseqNM_014874.4

mane_ensemblENST00000235329.10

External recordsHGNC:16877OMIM 608507gnomADUniProt O95140ClinGenClinVar P/LPGeneReviewsOrphanetMANE NM_014874.4

EvidenceClinGen Definitive Charcot-Marie-Tooth disease type 2A2PanelApp Green

ClinVar Variants

Pathogenic and likely pathogenic variants in MFN2, as classified in ClinVar, are read live from NCBI. Only aggregate germline records are shown. Uncertain and conflicting classifications are not. Experts in CMT makes no claim to the accuracy of ClinVar data. This index is provided for informational purposes only.

Review stars are ClinVar’s measure of how well a classification is supported: four for a practice guideline, three for an expert panel review, two for agreement among multiple submitters, one for a single submitter with criteria provided, and none where no criteria were provided.

Reported in CMT

Reported in Other Diseases

Reported in a disease other than CMT. Listed apart rather than counted as CMT variants.

Variants w/o a Recorded Disease

Pathogenic or likely pathogenic in ClinVar, submitted without a disease recorded.

The Dorsal Root

A Name That Does Too Much Work

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When Medicine Lost Its Compass

Evidence failed not because it was wrong, but because it was weaponized. I lived the downstream effects of that failure for more than a decade. This is what happens when medicine forgets that data always ends in a human being.

Error 404: Gene Not Found

CMT genetic testing often fails to identify the cause of the disease, even when comprehensive panels are used. Here, we discuss why this happens, what genetic tests can and cannot do, and why a negative result still matters.