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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MFN1
mitofusin 1
Chromosome 3 · 3q26.33
NCBI Gene: 55669Ensembl: ENSG00000171109.20HGNC: HGNC:18262UniProt: Q8IWA4
114PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GTPase activityprotein bindingmitochondrion localizationmitochondrial outer membraneneurodegenerative diseasepyogenic granulomaUterine leiomyomabreast carcinoma
✦AI Summary

MFN1 (mitofusin 1) is a mitochondrial outer membrane GTPase that plays a crucial role in mitochondrial fusion and dynamics 1. The protein mediates mitochondrial fusion by forming homotypic and heterotypic complexes with MFN2, with both proteins being essential for maintaining mitochondrial network integrity 1. MFN1 functions through GTPase activity to promote outer mitochondrial membrane fusion, and embryonic fibroblasts lacking MFN1 display severely fragmented mitochondria due to reduced fusion capacity 1. The protein is critical for embryonic development, as MFN1-deficient mice die in midgestation 1. Beyond its fusion role, MFN1 participates in the senescence-associated secretory phenotype (SASP) by facilitating mitochondrial dsRNA release into the cytosol, which drives inflammatory responses in senescent cells 2. Dysregulation of MFN1 and mitochondrial dynamics has been implicated in various diseases including heart disease, type 2 diabetes, and cancer 34. Additionally, MFN1 can be inhibited by proteins like FUNDC2 in cancer cells, leading to mitochondrial fragmentation that promotes tumorigenesis 5. The protein's function is essential for maintaining mitochondrial membrane potential and overall cellular health 1.

Sources cited
1
MFN1 is essential for mitochondrial fusion, embryonic development, and forms functional complexes with MFN2
PMID: 12527753
2
MFN1 participates in senescence-associated inflammatory responses through mitochondrial dsRNA release
PMID: 39191740
3
MFN1 dysfunction is implicated in cardiac diseases including heart failure and cardiomyopathies
PMID: 37895224
4
MFN1 dysregulation is associated with mitochondrial dysfunction in type 2 diabetes
PMID: 28131082
5
MFN1 can be inhibited by FUNDC2 in cancer, leading to mitochondrial fragmentation and tumorigenesis
PMID: 35710796
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.51Moderate
pyogenic granulomaOpen Targets
0.27Weak
Uterine leiomyomaOpen Targets
0.22Weak
breast carcinomaOpen Targets
0.21Weak
neoplasmOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
heart failureOpen Targets
0.08Suggestive
pulmonary fibrosisOpen Targets
0.08Suggestive
IGA glomerulonephritisOpen Targets
0.07Suggestive
chronic lymphocytic leukemiaOpen Targets
0.07Suggestive
triple-negative breast cancerOpen Targets
0.06Suggestive
periodontal disorderOpen Targets
0.05Suggestive
dengue diseaseOpen Targets
0.05Suggestive
infectionOpen Targets
0.05Suggestive
melanomaOpen Targets
0.05Suggestive
benign prostatic hyperplasiaOpen Targets
0.04Suggestive
cytomegalovirus infectionOpen Targets
0.04Suggestive
lung cancerOpen Targets
0.04Suggestive
Glucose intoleranceOpen Targets
0.03Suggestive
atrial fibrillationOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TOMM5Protein interaction100%SQSTM1Protein interaction100%DENRProtein interaction100%MFFProtein interaction99%MAVSProtein interaction98%TRAK1Protein interaction96%
Tissue Expression6 tissues
Heart
100%
Ovary
44%
Lung
42%
Bone Marrow
40%
Liver
33%
Brain
26%
Gene Interaction Network
Click a node to explore
MFN1TOMM5SQSTM1DENRMFFMAVSTRAK1
PROTEIN STRUCTURE
Preparing viewer…
PDB5GOF · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.95LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.76 [0.61–0.95]
RankingsWhere MFN1 stands among ~20K protein-coding genes
  • #4,154of 20,598
    Most Researched114 · top quartile
  • #8,960of 17,882
    Most Constrained (LOEUF)0.95
Genes detectedMFN1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Molecular mechanisms of mitochondrial dynamics.
PMID: 39420231
Nat Rev Mol Cell Biol · 2025
1.00
2
Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development.
PMID: 12527753
J Cell Biol · 2003
0.90
3
Role of Mitochondrial Dynamics in Heart Diseases.
PMID: 37895224
Genes (Basel) · 2023
0.80
4
Mitochondrial dynamics in health and disease.
PMID: 33742459
FEBS Lett · 2021
0.70
5
Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications.
PMID: 28131082
Redox Biol · 2017
0.60