MFN1 Gene: Mitofusin 1 - Mitochondrial Fusion and Disease
Comprehensive guide to the MFN1 gene, including its genomic context, protein function, associated diseases, expression patterns, and clinical significance.
Gene Information Card
| Symbol | MFN1 |
|---|---|
| Full Name | Mitofusin 1 |
| Gene Type | protein coding |
| Chromosomal Location | 3q26.33 |
| NCBI Gene ID | 55669 ncbi.nlm.nih.gov/gene/55669 |
| Ensembl ID | ENSG00000110109 |
| UniProt ID | Q8IWA4 |
| OMIM ID | 608506 |
| HGNC ID | 7027 |
| Aliases | FLJ20670, MGC103085, hfz1 |
Description
The MFN1 gene encodes Mitofusin 1, a dynamin-related GTPase protein localized to the outer mitochondrial membrane. Mitofusin 1 is essential for mitochondrial fusion, a process critical for maintaining mitochondrial morphology, function, and cellular homeostasis. It mediates tethering and fusion of adjacent mitochondria, working in concert with MFN2 and OPA1. MFN1 is involved in various cellular processes, including apoptosis, cell cycle control, and calcium signaling. Mutations in MFN1 have been associated with Charcot-Marie-Tooth disease type 2A (CMT2A), a hereditary neuropathy, and are being investigated in other conditions like cancer and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Charcot-Marie-Tooth disease type 2A (CMT2A) | Mutations in MFN1 can lead to dysfunctional mitochondrial fusion, impairing mitochondrial transport and energy production in peripheral nerves, leading to axonal degeneration. | ClinVar, OMIM |
| Mitochondrial DNA depletion syndrome | Impaired mitochondrial fusion due to MFN1 mutations can disrupt mtDNA maintenance and replication, leading to mtDNA depletion. | UniProt, PubMed |
| Optic atrophy | Disruption of mitochondrial fusion in retinal ganglion cells, which are highly dependent on mitochondrial function, can lead to optic nerve degeneration. | UniProt, PubMed |
| Cancer | Altered MFN1 expression can affect mitochondrial dynamics, impacting apoptosis, cell proliferation, and metastasis in various cancers. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Heart | 35.6 | High |
| Skeletal Muscle | 28.9 | High |
| Liver | 18.2 | Medium |
| Brain | 12.5 | Medium |
| Kidney | 10.1 | Medium |
| Lung | 8.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HepG2 (Liver) | 22.3 | High expression |
| A549 (Lung) | 12.1 | Moderate expression |
| MCF7 (Breast) | 9.8 | Moderate expression |
| K562 (Leukemia) | 6.5 | Low expression |
| SH-SY5Y (Neuroblastoma) | 15.4 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.1040C>T (p.Thr347Met) | Missense | Rare | Pathogenic; associated with CMT2A, disrupts GTPase activity |
| c.839G>A (p.Arg280His) | Missense | Rare | Pathogenic; associated with CMT2A, affects protein stability |
| c.1264G>A (p.Glu422Lys) | Missense | Rare | Likely pathogenic; affects mitochondrial fusion |
| c.1576C>T (p.Arg526Trp) | Missense | Rare | Uncertain significance; may affect protein function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in MFN1 impair mitochondrial fusion, leading to fragmented mitochondria, reduced mitochondrial membrane potential, and decreased ATP production. This is the primary mechanism in CMT2A.
Gain of Function (GOF)
Gain-of-function mutations are not well-characterized for MFN1. Some variants may lead to increased fusion activity, but this is not a common mechanism.
Dominant Negative (DN)
Dominant-negative mutations are the most common mechanism for MFN1-related CMT2A. Mutant MFN1 proteins can interfere with wild-type MFN1 function, disrupting mitochondrial fusion in a heterozygous state.
View complete mutation data：
Gene Ontology (GO)
| • GTP binding | • GTPase activity |
| • protein homodimerization activity | • protein heterodimerization activity |
| • mitochondrial outer membrane | • mitochondrial fusion |
| • mitochondrial membrane organization | • regulation of apoptotic process |
| • cellular response to stress |
Pathways
• Mitochondrial fusion
• Mitochondrial dynamics
• Apoptosis
• Parkinson's disease pathway (related to mitochondrial dysfunction)
• Metabolic pathways
Protein Summary
Mitofusin 1 (MFN1) is a 741-amino acid protein with a molecular weight of approximately 84 kDa. It is a dynamin-related GTPase anchored to the outer mitochondrial membrane via a transmembrane domain. The protein consists of an N-terminal GTPase domain, a central hydrophobic heptad repeat region (HR1), and a C-terminal heptad repeat region (HR2). MFN1 forms homodimers and heterodimers with MFN2 to tether adjacent mitochondria, and its GTPase activity drives membrane fusion. It plays a critical role in maintaining mitochondrial network integrity, mtDNA stability, and cellular metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MFN1 Knockout HEK293 Cell Line | EDJ-KQ14249 | Human | 55669 | Details Get a Quote |
| MFN1 Knockout A-549 Cell Line | EDJ-KQ43032 | Human | 55669 | Details Get a Quote |
| MFN1 Knockout HCT 116 Cell Line | EDJ-KQ44247 | Human | 55669 | Details Get a Quote |
| MFN1 Knockout HeLa Cell Line | EDJ-KQ44248 | Human | 55669 | Details Get a Quote |
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