MFF Gene: Mitochondrial Fission Factor – Function, Disease Associations, and Clinical Significance
Comprehensive resource on the MFF gene, covering its genomic context, protein function, expression patterns, disease links, and mutation landscape, based on authoritative databases.
Gene Information Card
| Symbol | MFF |
|---|---|
| Full Name | Mitochondrial Fission Factor |
| Gene Type | Protein coding |
| Chromosomal Location | 2q36.3 |
| NCBI Gene ID | 56947 ncbi.nlm.nih.gov/gene/56947 |
| Ensembl ID | ENSG00000168958 |
| UniProt ID | Q9GZY8 |
| OMIM ID | 614785 |
| HGNC ID | 24552 |
| Aliases | C2orf33, FLJ36458, MGC125632 |
Description
The MFF gene encodes the Mitochondrial Fission Factor, a C-terminal tail-anchored protein localized to the mitochondrial outer membrane. MFF serves as a critical receptor for Dynamin-1-Like Protein (DNM1L/DRP1), recruiting it from the cytosol to the mitochondrial surface to initiate mitochondrial fission. This process is essential for mitochondrial quality control, distribution, and clearance. MFF is also involved in peroxisomal fission. Mutations in MFF cause an autosomal recessive neurological disorder characterized by developmental delay, optic atrophy, and peripheral neuropathy, known as Encephalopathy due to defective mitochondrial and peroxisomal fission 2 (EMPF2).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Encephalopathy due to defective mitochondrial and peroxisomal fission 2 (EMPF2) | Loss-of-function mutations in MFF impair the recruitment of DRP1 to mitochondria, leading to excessive mitochondrial elongation, reduced mitochondrial fission, and impaired mitochondrial distribution in neurons. This disrupts mitochondrial function and leads to neurodegeneration. | OMIM (614785), ClinVar, PubMed (e.g., Shamseldin et al., 2012; Koch et al., 2016) |
| Optic atrophy and peripheral neuropathy | A core feature of EMPF2, resulting from the impaired mitochondrial dynamics in highly energy-dependent cells like retinal ganglion cells and peripheral neurons. | ClinVar, PubMed (e.g., Koch et al., 2016) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Skeletal Muscle | ~25.0 | High |
| Heart | ~20.0 | High |
| Liver | ~15.0 | Medium |
| Brain (Cerebellum) | ~12.0 | Medium |
| Kidney | ~10.0 | Medium |
| Lung | ~5.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HepG2 (Liver) | ~18.0 | High expression, consistent with high metabolic activity. |
| K-562 (Leukemia) | ~12.0 | Moderate expression. |
| A549 (Lung) | ~8.0 | Moderate expression. |
| MCF7 (Breast) | ~6.0 | Lower expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.579+1G>A (IVS5+1G>A) | Splice-site | Rare (found in affected families) | Skipping of exon 5, leading to a frameshift and premature termination codon. Results in a truncated, non-functional MFF protein. |
| c.650C>T (p.Pro217Leu) | Missense | Rare (found in affected families) | Substitution of a highly conserved proline residue in the cytoplasmic domain, likely disrupting protein folding or interaction with DRP1. |
| c.835C>T (p.Arg279*) | Nonsense | Rare (found in affected families) | Introduces a premature stop codon, leading to a severely truncated protein that lacks the transmembrane domain and is likely degraded. |
Mutation functional classification
Loss of Function (LOF)
The majority of disease-associated MFF mutations are loss-of-function. They result in reduced or absent MFF protein, leading to impaired DRP1 recruitment and defective mitochondrial fission. This is the primary mechanism for EMPF2.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MFF in the context of human disease.
Dominant Negative (DN)
No dominant-negative mutations have been reported for MFF. The inheritance pattern for MFF-related disorders is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • Mitochondrial fission | • Peroxisome fission |
| • Protein homodimerization activity | • Mitochondrial outer membrane |
| • Peroxisomal membrane | • Dynamin family protein binding |
| • Regulation of mitochondrial membrane potential |
Pathways
• Mitochondrial fission
• Peroxisomal fission
• Mitochondrial dynamics
Protein Summary
The MFF protein is a 342-amino acid tail-anchored protein of the mitochondrial outer membrane. It consists of a short N-terminal cytoplasmic domain, a single transmembrane domain, and a short C-terminal segment exposed to the intermembrane space. The cytoplasmic domain contains a coiled-coil region that mediates homodimerization and interaction with the GTPase DRP1. MFF acts as a receptor that recruits DRP1 from the cytosol to the mitochondrial surface, where DRP1 oligomerizes and drives membrane constriction and fission. MFF also plays a role in peroxisomal fission. Its activity is regulated by post-translational modifications, including phosphorylation, which can modulate its affinity for DRP1.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MFF Knockout HEK293 Cell Line | EDJ-KQ11968 | Human | 56947 | Details Get a Quote |
| MFF Knockout A-549 Cell Line | EDJ-KQ40522 | Human | 56947 | Details Get a Quote |
| MFF Knockout HCT 116 Cell Line | EDJ-KQ40523 | Human | 56947 | Details Get a Quote |
| MFF Knockout HeLa Cell Line | EDJ-KQ40524 | Human | 56947 | Details Get a Quote |
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