Gene: MFN2

Alternate names for this Gene: CMT2A|CMT2A2|CMT2A2A|CMT2A2B|CPRP1|HMSN6A|HSG|MARF

Gene Summary: 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.

Gene is located in Chromosome: 1

Location in Chromosome : 1p36.22

Description of this Gene: mitofusin 2

Type of Gene: protein-coding

rs119103267 in MFN2 gene and CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2A2A PMID 30158064 2019 MFN2-associated lipomatosis: Clinical spectrum and impact on adipose tissue.

PMID 28414270 2017 Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression.

PMID 26114802 2015 MFN2 deletion of exons 7 and 8: founder mutation in the UK population.

PMID 22492563 2012 MFN2 mutations cause compensatory mitochondrial DNA proliferation.

PMID 26085578 2015 Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy.

PMID 20008656 2009 Genotype-phenotype correlations in Charcot-Marie-Tooth disease type 2 caused by mitofusin 2 mutations.

PMID 20350294 2010 MFN2 point mutations occur in 3.4% of Charcot-Marie-Tooth families. An investigation of 232 Norwegian CMT families.

PMID 29358271 2018 Catalogue of inherited disorders found among the Irish Traveller population.

PMID 24126688 2013 Spectrum and frequencies of mutations in the MFN2 gene and its phenotypical expression in Czech hereditary motor and sensory neuropathy type II patients.

PMID 25025039 2014 Genetic diagnosis of Charcot-Marie-Tooth disease in a population by next-generation sequencing.

PMID 18458227 2008 Severe early-onset axonal neuropathy with homozygous and compound heterozygous MFN2 mutations.

PMID 28251916 2017 Genetic heterogeneity of motor neuropathies.

PMID 15064763 2004 Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A.

PMID 16762064 2006 Charcot-Marie-Tooth neuropathy type 2A: novel mutations in the mitofusin 2 gene (MFN2).

PMID 15549395 2005 Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth neuropathy type 2A.

PMID 22206013 2011 The mutational spectrum in a cohort of Charcot-Marie-Tooth disease type 2 among the Han Chinese in Taiwan.

PMID 26257172 2015 Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy.

PMID 26378787 2016 The role of combined SNV and CNV burden in patients with distal symmetric polyneuropathy.

PMID 21326314 2011 Molecular diagnosis and clinical onset of Charcot-Marie-Tooth disease in Japan.

PMID 24053775 2013 Diagnostic laboratory testing for Charcot Marie Tooth disease (CMT): the spectrum of gene defects in Norwegian patients with CMT and its implications for future genetic test strategies.

rs119103267 in MFN2 gene and CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL RECESSIVE, TYPE 2A2B PMID 26085578 2015 Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy.

PMID 26955893 2016 Autosomal recessive MFN2-related Charcot-Marie-Tooth disease with diaphragmatic weakness: Case report and literature review.

PMID 20350294 2010 MFN2 point mutations occur in 3.4% of Charcot-Marie-Tooth families. An investigation of 232 Norwegian CMT families.

PMID 18458227 2008 Severe early-onset axonal neuropathy with homozygous and compound heterozygous MFN2 mutations.

PMID 21715711 2011 Recessive axonal Charcot-Marie-Tooth disease due to compound heterozygous mitofusin 2 mutations.

PMID 16835246 2006 Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations.

rs119103268 in MFN2 gene and Charcot-Marie-Tooth Disease PMID 25025039 2014 Genetic diagnosis of Charcot-Marie-Tooth disease in a population by next-generation sequencing.

PMID 18425620 2008 Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.

PMID 21840889 2011 Genetic spectrum of hereditary neuropathies with onset in the first year of life.

PMID 21531138 2011 Characterizing the phenotypic manifestations of MFN2 R104W mutation in Charcot-Marie-Tooth type 2.

PMID 16714318 2006 MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2.

rs6686734 in MFN2 gene and Dermatitis, Atopic PMID 25574825 2015 Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.

rs1060501915 in MFN2 gene and Hereditary Motor and Sensory-Neuropathy Type II PMID 21508331 2011 MFN2 mutations cause severe phenotypes in most patients with CMT2A.

PMID 24819634 2014 Mutation analysis of MFN2, GJB1, MPZ and PMP22 in Italian patients with axonal Charcot-Marie-Tooth disease.

PMID 16714318 2006 MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2.

PMID 24126688 2013 Spectrum and frequencies of mutations in the MFN2 gene and its phenotypical expression in Czech hereditary motor and sensory neuropathy type II patients.

PMID 17309650 2007 Mitochondrial GTPase mitofusin 2 mutations in Korean patients with Charcot-Marie-Tooth neuropathy type 2.

PMID 16835246 2006 Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations.

PMID 27549087 2016 Improving diagnosis of inherited peripheral neuropathies through gene panel analysis.

PMID 21285398 2011 Bioenergetic defect associated with mKATP channel opening in a mouse model carrying a mitofusin 2 mutation.

PMID 15064763 2004 Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A.

PMID 19889647 2010 Phenotypic spectrum of MFN2 mutations in the Spanish population.

PMID 16437557 2006 Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2.

PMID 24604904 2014 Application of whole exome sequencing in undiagnosed inherited polyneuropathies.

PMID 24862862 2014 Characterization of the mitofusin 2 R94W mutation in a knock-in mouse model.

PMID 26686600 2016 Clinical and allelic heterogeneity in a pediatric cohort of 11 patients carrying MFN2 mutation.

PMID 22442078 2012 Mitofusin2 mutations disrupt axonal mitochondrial positioning and promote axon degeneration.

PMID 25448007 2015 Axonal Charcot-Marie-Tooth disease patient-derived motor neurons demonstrate disease-specific phenotypes including abnormal electrophysiological properties.

PMID 22206013 2011 The mutational spectrum in a cohort of Charcot-Marie-Tooth disease type 2 among the Han Chinese in Taiwan.

PMID 28063088 2017 Mosaicism for a pathogenic MFN2 mutation causes minimal clinical features of CMT2A in the parent of a severely affected child.

PMID 21707411 2011 Structural and functional measures of inner retinal integrity following visual acuity improvement in a patient with hereditary motor and sensory neuropathy type VI.

PMID 25802885 2015 Improved inherited peripheral neuropathy genetic diagnosis by whole-exome sequencing.

PMID 22492563 2012 MFN2 mutations cause compensatory mitochondrial DNA proliferation.

PMID 28414270 2017 Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression.

PMID 20008656 2009 Genotype-phenotype correlations in Charcot-Marie-Tooth disease type 2 caused by mitofusin 2 mutations.

PMID 184582 1976 Giant cell tumor of soft parts. An ultrastructural study.

PMID 26085578 2015 Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy.

PMID 20350294 2010 MFN2 point mutations occur in 3.4% of Charcot-Marie-Tooth families. An investigation of 232 Norwegian CMT families.

PMID 26114802 2015 MFN2 deletion of exons 7 and 8: founder mutation in the UK population.

PMID 25025039 2014 Genetic diagnosis of Charcot-Marie-Tooth disease in a population by next-generation sequencing.

PMID 21531138 2011 Characterizing the phenotypic manifestations of MFN2 R104W mutation in Charcot-Marie-Tooth type 2.

PMID 26307494 2015 Early onset Charcot-Marie-Tooth neuropathy type 2A and severe developmental delay: expanding the clinical phenotype of MFN2-related neuropathy.

PMID 26382835 2015 A cohort study of Han Chinese MFN2-related Charcot-Marie-Tooth 2A.

PMID 21840889 2011 Genetic spectrum of hereditary neuropathies with onset in the first year of life.

PMID 18425620 2008 Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.

PMID 18946002 2008 Mutated mitofusin 2 presents with intrafamilial variability and brain mitochondrial dysfunction.

PMID 18957892 2008 Histopathological findings in hereditary motor and sensory neuropathy of axonal type with onset in early childhood associated with mitofusin 2 mutations.

PMID 21326314 2011 Molecular diagnosis and clinical onset of Charcot-Marie-Tooth disease in Japan.

PMID 24957169 2014 Charcot-Marie-Tooth disease type 2A: from typical to rare phenotypic and genotypic features.

PMID 17296794 2007 Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations.

PMID 16043786 2005 Clinical and electrophysiologic features of CMT2A with mutations in the mitofusin 2 gene.

PMID 19812251 2009 A mutation associated with CMT2A neuropathy causes defects in Fzo1 GTP hydrolysis, ubiquitylation, and protein turnover.

PMID 17959936 2008 Hindlimb gait defects due to motor axon loss and reduced distal muscles in a transgenic mouse model of Charcot-Marie-Tooth type 2A.

PMID 18316077 2008 Mitochondrial fusion and function in Charcot-Marie-Tooth type 2A patient fibroblasts with mitofusin 2 mutations.

PMID 26955893 2016 Autosomal recessive MFN2-related Charcot-Marie-Tooth disease with diaphragmatic weakness: Case report and literature review.

PMID 21715711 2011 Recessive axonal Charcot-Marie-Tooth disease due to compound heterozygous mitofusin 2 mutations.

PMID 27862672 2017 Clinical and genetic spectra of Charcot-Marie-Tooth disease in Chinese Han patients.

PMID 24078732 2013 Charcot-Marie-Tooth disease: genetic and clinical spectrum in a Spanish clinical series.

PMID 21258814 2011 Mutation screening of mitofusin 2 in Charcot-Marie-Tooth disease type 2.

PMID 15549395 2005 Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth neuropathy type 2A.

PMID 18996695 2008 Two Spanish families with Charcot-Marie-Tooth type 2A: clinical, electrophysiological and molecular findings.

PMID 17437620 2007 Mitofusin 2 gene mutation (R94Q) causing severe early-onset axonal polyneuropathy (CMT2A).

PMID 10732809 1997 Confirmation of a second locus for CMT2 and evidence for additional genetic heterogeneity.

PMID 20335458 2010 Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex.

PMID 25614874 2014 The allelic spectrum of Charcot-Marie-Tooth disease in over 17,000 individuals with neuropathy.

PMID 17215403 2007 Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth disease from mitofusin 2 mutations.

PMID 24863639 2015 A cohort study of MFN2 mutations and phenotypic spectrums in Charcot-Marie-Tooth disease 2A patients.

PMID 19350291 2009 A novel de novo MFN2 mutation causing CMT2A with upper motor neuron signs.

PMID 24627108 2014 Whole-exome sequencing in patients with inherited neuropathies: outcome and challenges.

PMID 25957633 2015 Acute optic neuropathy associated with a novel MFN2 mutation.

PMID 24450158 2013 [MFN2 gene analysis in patients with hereditary motor and sensory neuropathy from Bashkortostan Republic].

PMID 26989944 2016 Charcot-Marie-Tooth type 2 and distal hereditary motor neuropathy: Clinical, neurophysiological and genetic findings from a single-centre experience.

PMID 25403865 2014 Exome sequencing reveals mutations in MFN2 and GDAP1 in severe Charcot-Marie-Tooth disease.

PMID 27100445 2016 Rapidly Progressive Polyneuropathy in a Patient With Monoclonal Gammopathy: A Case Report of POEMS Syndrome and Beyond.

PMID 26801520 2016 MFN2-related genetic and clinical features in a cohort of Chinese CMT2 patients.

PMID 24473995 2014 Chronic and slowly progressive weakness of the legs and hands.

PMID 22926664 2013 Mitofusin 2 mutations affect mitochondrial function by mitochondrial DNA depletion.

PMID 22851605 2012 Comprehensive analysis of the TRPV4 gene in a large series of inherited neuropathies and controls.

PMID 28251916 2017 Genetic heterogeneity of motor neuropathies.

PMID 16762064 2006 Charcot-Marie-Tooth neuropathy type 2A: novel mutations in the mitofusin 2 gene (MFN2).

PMID 20951041 2011 Co-occurrence of amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease type 2A in a patient with a novel mutation in the mitofusin-2 gene.

PMID 16087932 2005 Charcot-Marie-Tooth with pyramidal signs is genetically heterogeneous: families with and without MFN2 mutations.

PMID 26378787 2016 The role of combined SNV and CNV burden in patients with distal symmetric polyneuropathy.

PMID 26257172 2015 Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy.

PMID 17444508 2007 Mitochondrial coupling defect in Charcot-Marie-Tooth type 2A disease.

rs28940291 in MFN2 gene and Hereditary motor and sensory neuropathy with optic atrophy (disorder) PMID 24604904 2014 Application of whole exome sequencing in undiagnosed inherited polyneuropathies.

PMID 20350294 2010 MFN2 point mutations occur in 3.4% of Charcot-Marie-Tooth families. An investigation of 232 Norwegian CMT families.

PMID 26085578 2015 Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy.

PMID 16437557 2006 Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2.

rs730123 in MFN2 gene and Homocysteine measurement PMID 30339177 2018 The 677C→T variant of MTHFR is the major genetic modifier of biomarkers of folate status in a young, healthy Irish population.

rs2336384 in MFN2 gene and Platelet Count measurement PMID 22139419 2011 New gene functions in megakaryopoiesis and platelet formation.

rs4240897 in MFN2 gene and Tuberculosis PMID 29036319 2017 After replication on an additional 3460 TB patients and 4862 controls (stages 2 and 3), we identified three significant loci associated with TB, the most significant of which was rs4240897 (logistic regression P = 1.41 × 10-11, odds ratio = 0.79).