MFN1

Summary

MFN1 (mitofusin 1, HGNC:18262) is a protein-coding gene on chromosome 3q26.33, encoding Mitofusin-1 (Q8IWA4). Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion.

The protein encoded by this gene is a mediator of mitochondrial fusion. This protein and mitofusin 2 are homologs of the Drosophila protein fuzzy onion (Fzo). They are mitochondrial membrane proteins that interact with each other to facilitate mitochondrial targeting.

Source: NCBI Gene 55669 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 110 total
• MANE Select transcript: NM_033540

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18262
Approved symbol	MFN1
Name	mitofusin 1
Location	3q26.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20693
Ensembl gene	ENSG00000171109
Ensembl biotype	protein_coding
OMIM	608506
Entrez	55669

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 20 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000263969, ENST00000357390, ENST00000466287, ENST00000467174, ENST00000471841, ENST00000474903, ENST00000480636, ENST00000482661, ENST00000489329, ENST00000897667, ENST00000897668, ENST00000897669, ENST00000897670, ENST00000897671, ENST00000931925, ENST00000931926, ENST00000969612, ENST00000969613, ENST00000969614, ENST00000969615, ENST00000969616, ENST00000969617, ENST00000969618, ENST00000969619

RefSeq mRNA: 1 — MANE Select: NM_033540 NM_033540

CCDS: CCDS3228

Canonical transcript exons

ENST00000471841 — 18 exons

Exon	Start	End
ENSE00000826318	179364297	179364405
ENSE00000826319	179365118	179365225
ENSE00000826323	179367439	179367592
ENSE00000826325	179368036	179368103
ENSE00001128192	179377042	179377168
ENSE00001206459	179347709	179347810
ENSE00001267382	179358840	179359002
ENSE00001267389	179351900	179352035
ENSE00001267446	179375220	179375341
ENSE00001267561	179348845	179348963
ENSE00001913085	179391981	179394936
ENSE00003534687	179377344	179377448
ENSE00003545322	179390004	179390138
ENSE00003553416	179362358	179362482
ENSE00003559662	179385569	179385721
ENSE00003624996	179378341	179378443
ENSE00003631187	179386433	179386629
ENSE00003686814	179378585	179378814

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 97.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.6302 / max 598.3145, expressed in 1815 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39925	26.3818	1808
39926	4.1099	1427
39927	0.1385	32

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.43	gold quality
oocyte	CL:0000023	96.57	gold quality
calcaneal tendon	UBERON:0003701	95.96	gold quality
body of pancreas	UBERON:0001150	95.70	gold quality
mucosa of stomach	UBERON:0001199	93.21	gold quality
pancreas	UBERON:0001264	93.00	gold quality
colonic epithelium	UBERON:0000397	92.85	gold quality
metanephros cortex	UBERON:0010533	92.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.48	gold quality
right uterine tube	UBERON:0001302	92.31	gold quality
adrenal tissue	UBERON:0018303	92.30	gold quality
right atrium auricular region	UBERON:0006631	92.21	gold quality
skin of leg	UBERON:0001511	91.96	gold quality
cardiac atrium	UBERON:0002081	91.83	gold quality
endocervix	UBERON:0000458	91.79	gold quality
skin of abdomen	UBERON:0001416	91.73	gold quality
cerebellar hemisphere	UBERON:0002245	91.64	gold quality
body of uterus	UBERON:0009853	91.53	gold quality
esophagus mucosa	UBERON:0002469	91.51	gold quality
cerebellar cortex	UBERON:0002129	91.48	gold quality
minor salivary gland	UBERON:0001830	91.46	gold quality
descending thoracic aorta	UBERON:0002345	91.40	gold quality
body of stomach	UBERON:0001161	91.38	gold quality
heart left ventricle	UBERON:0002084	91.14	gold quality
ectocervix	UBERON:0012249	91.13	gold quality
heart	UBERON:0000948	91.12	gold quality
vagina	UBERON:0000996	91.10	gold quality
thoracic aorta	UBERON:0001515	91.04	gold quality
esophagus	UBERON:0001043	91.01	gold quality
cardiac ventricle	UBERON:0002082	91.01	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	3830.37
E-MTAB-3929	yes	533.63
E-ANND-3	yes	8.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PID1

Literature-anchored findings (GeneRIF, showing 40)

• Results show that Fzo homologs mitofusin 1 and 2 are ubiquitous mitochondrial membrane proteins that interact with each other to facilitate mitochondrial targeting. (PMID:11950885)
• Mfn1 mediates mitochondrial fusion in human cells (PMID:12475957)
• OPA1 functionally requires mitofusin 1 to regulate mitochondrial fusion (PMID:15509649)
• Mfn1, Mfn2, NRF-2 and COX IV mRNA were increased 24 h post-exercise in skeletal muscle (PMID:15961417)
• Precise interactions between a few proteins are required for mitochondrial fusion and division. Among them Drp1, Mfn1, Mfn2 and Opal are considered the most important. (PMID:17718388)
• Fis1 and Mfn1 activities influence mitochondrial signal generation thereby insulin exocytosis. (PMID:18832378)
• IL-6 induces Bcl-2 expression to perform cytoprotective functions in response to oxygen toxicity, and that this effect is mediated by alterations in the interactions between Bak and Mfn1/Mfn2. Bcl-2 inhibited the interaction between Bak and Mfn1. (PMID:19168699)
• lack of MARCH5 results in mitochondrial elongation, which promotes cellular senescence by blocking Drp1 activity and/or promoting accumulation of Mfn1 at the mitochondria (PMID:20103533)
• the NIC-Akt-Mfn signaling cascade identifies a pathway regulating cell-survival, independent of canonical functions associated with NIC activity (PMID:20339081)
• MFN1 is required for both the virus-induced redistribution of IPS-1 and IFN production. (PMID:20661427)
• Ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2 were reduced following the silencing of parkin or PINK1. (PMID:20871098)
• Patterned Purkinje cell degeneration is dependent on caspase activation, leading to the marked decrease of mitofusion 1 in the transgenic Harlequin cerebellum. (PMID:20974255)
• Gbeta2 also regulated the mobility of Mfn1 on the surface of the mitochondrial membrane and affected the mitochondrial fusion. (PMID:20981029)
• Mitofusin degradation by mitochondria-associated Parkin inhibits the fusion of damaged mitochondria with healthy mitochondria to facilitate the selective elimination of the former by autophagy. (PMID:21173115)
• The impact of mutations in endogenous PINK1 and Parkin on the ubiquitination of mitochondrial fusion and fission factors and the mitochondrial network structure, was investigated. (PMID:21408142)
• Our data supports a model whereby the translocation of parkin to damaged mitochondria induces the degradation of mitofusin 1 leading to impaired mitochondrial fusion (PMID:21615408)
• mitochondrial dynamics, particularly those mediated by the mitofusins, play a role in endothelial cell function and viability. (PMID:21839087)
• These results collectively suggest a role for Mfn1 in regulating the activation of Bax on the outer mitochondrial membrane in a GTPase-dependent manner. (PMID:22484496)
• Knock-out of mitofusin protein Mfn1 increased the frequency of mitochondrial fission with increased lifetime of unpaired events whereas deletion of both Mfn1 and Mfn2 resulted in an instable dynamics. (PMID:22649485)
• A novel role for the endoplasmic reticulum-associated Gp78 ubiquitin ligase and the Mfn1 mitochondrial fusion factor in mitophagy. (PMID:23427266)
• In a amyotrophic lateral sclerosis transgenic mouse model, Mfn1 is significantly increased in spinal cord. (PMID:23713734)
• A fine balance of Mfn1 levels is maintained by MARCH5-mediated quality control on acetylated Mfn1. (PMID:24722297)
• miR-19b targets 3’UTR sequences of Mfn1 genes inhibit the expression of Mfn1 (PMID:24824927)
• Improper transcriptional (in)activation of mitofusin-1 and dynamin-related protein 1 during early in vitro embryo development is associated with a decrease in mitochondrial membrane potential and with embryo fragmentation. (PMID:25033890)
• MFN1-positive expression could be seen mainly in ganglion cells after 1 week of minus lens intervention, and with time extension, more and more positive cells appeared in the rod-cone cell and bipolar cell layer, and this phenomenon could not be found in the normal control eyes. (PMID:27609161)
• Regulation of Mfn1 by MGRN1 and the proteasome modulates mitochondrial fusion. (PMID:27713096)
• These results suggest that MFN tethers apposing membranes, likely through nucleotide-dependent dimerization. (PMID:27920125)
• SLC25A46 is a new component in mitochondrial dynamics that serves as a regulator for MFN1/2 oligomerization. (PMID:28057766)
• crystal structures of engineered human MFN1 containing the GTPase domain and a helical domain during different stages of GTP hydrolysis; mechanistic model for MFN1-mediated mitochondrial tethering is proposed; results shed light on the molecular basis of mitochondrial fusion and mitofusin-related human neuromuscular disorders (PMID:28114303)
• mitochondria elongation under hypoxic condition is regulated through SIRT1-mediated MFN1 deacetylation and accumulation. (PMID:28669827)
• The results show that a metabolic shift from glycolysis in young to mitochondrial respiration in old normal human fibroblasts occurs during chronological lifespan, and MFN1 and OPA1 regulate this process. (PMID:28758339)
• The results lead to a revised understanding of Mfn 1 as single-spanning outer membrane proteins with an Nout-Cin orientation, providing functional insight into the IMS contribution to redox-regulated fusion events. (PMID:29212658)
• Structural basis for how MFN1 mediates homotypic membrane fusion. (PMID:29483649)
• heptad repeat domain of Mitofusin proteins induces membrane fusion and possesses a conserved amphipathic helix that folds upon interaction with the lipid bilayer surface. (PMID:29661855)
• The results may suggest that TP53BP1 and MFN1 frameshift mutations and their intratumoral heterogeneity (ITH) could contribute to cancer development by inhibiting the TSG activities. (PMID:30082159)
• This study elucidates an essential role of MFN1 in stem cell fate determination to mediate EMT-associated stemness. (PMID:30527740)
• Human Mfn1 contains internal N-Terminal mitochondrial targeting sequence (MTS) localized in the loop region between the two helices of the conserved transmembrane domain. Internal MTS is a shared feature of all opisthokont mitofusins. It facilitates anchoring and targeting of these proteins to the mitochondrial membrane. (PMID:30635120)
• The mRNA upregulation of Mitofusin 1 and 2 provides first insight into the complex changes of mitochondrial dynamics in cardiomyocytes of patients with reversible heart failure due to tachycardiomyopathy. (PMID:30873819)
• Our results reveal a critical involvement of mitochondrial dynamics in hepatocellular carcinoma (HCC) metastasis via modulating glucose metabolic reprogramming. MFN1 may serve as a novel potential therapeutic target for HCC (PMID:31819189)
• Mitochondrial Fusion Via OPA1 and MFN1 Supports Liver Tumor Cell Metabolism and Growth. (PMID:31947947)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	MFN1	ENSDARG00000011884
danio_rerio	mfn1b	ENSDARG00000079219
mus_musculus	Mfn1	ENSMUSG00000027668
rattus_norvegicus	Mfn1	ENSRNOG00000011057
drosophila_melanogaster	Marf	FBGN0029870
caenorhabditis_elegans		WBGENE00001509

Paralogs (1): MFN2 (ENSG00000116688)

Protein

Protein identifiers

Mitofusin-1 — Q8IWA4 (reviewed: Q8IWA4)

Alternative names: Fzo homolog, Transmembrane GTPase MFN1

All UniProt accessions (4): C9JQT7, C9JXQ1, Q8IWA4, H7C5H5

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion. Membrane clustering requires GTPase activity. It may involve a major rearrangement of the coiled coil domains. 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 (in vitro). Has low GTPase activity.

Subunit / interactions. Homodimer, also in the absence of bound GTP. Forms higher oligomers in the presence of a transition state GTP analog. Forms homomultimers and heteromultimers with MFN2. Oligomerization is essential for mitochondrion fusion. Component of a high molecular weight multiprotein complex. Interacts with VAT1. Interacts with THG1L; THG1L probably functions as a guanyl-nucleotide exchange factor/GEF, activating MFN1.

Subcellular location. Mitochondrion outer membrane Cytoplasm.

Tissue specificity. Detected in kidney and heart (at protein level). Ubiquitous. Expressed at slightly higher level in kidney and heart. Isoform 2 may be overexpressed in some tumors, such as lung cancers.

Post-translational modifications. Ubiquitinated by non-degradative ubiquitin by PRKN. Deubiquitination by USP30 inhibits mitochondrial fusion. Ubiquitinated by MARCHF5. When mitochondria are depolarized and dysfunctional, it is ubiquitinated by a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that contains FBXO7 and PRKN.

Domain organisation. A helix bundle is formed by helices from the N-terminal and the C-terminal part of the protein. The GTPase domain cannot be expressed by itself, without the helix bundle. Rearrangement of the helix bundle and/or of the coiled coil domains may bring membranes from adjacent mitochondria into close contact, and thereby play a role in mitochondrial fusion.

Miscellaneous. A truncated MFN1 construct containing the GTPase domain and the associated helix bundle is a monomer in the absence of bound GTP and a homodimer in the GTP-bound form; GDP cannot replace GTP and induce dimerization.

Similarity. Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. Mitofusin subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IWA4-1	1, TG741	yes
Q8IWA4-2	2, TG370
Q8IWA4-3	3

RefSeq proteins (1): NP_284941* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006884	Fzo/mitofusin_HR2	Domain
IPR027094	Mitofusin_fam	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030381	G_DYNAMIN_dom	Domain
IPR045063	Dynamin_N	Domain

Pfam: PF00350, PF04799

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (90 total): mutagenesis site 21, helix 21, strand 12, region of interest 8, sequence conflict 7, binding site 4, topological domain 3, splice variant 3, turn 3, coiled-coil region 2, transmembrane region 2, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
5GOF	X-RAY DIFFRACTION	1.6
5GOE	X-RAY DIFFRACTION	1.8
5GO4	X-RAY DIFFRACTION	2.2
5GNR	X-RAY DIFFRACTION	2.65
5GNT	X-RAY DIFFRACTION	2.67
5GNS	X-RAY DIFFRACTION	2.7
5GOM	X-RAY DIFFRACTION	2.8
5YEW	X-RAY DIFFRACTION	3.2
5GNU	X-RAY DIFFRACTION	4.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWA4-F1	81.65	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 85–90; 237–240; 284; 286

Mutagenesis-validated functional residues (21):

Position	Phenotype
15	decreases gtpase activity. impairs mitochondrial fusion.
74	mildly decreases gtpase activity and impairs mitochondrial fusion.
88	abolishes gtpase activity. abolishes dimerization.
88	induces a strong decrease in mitochondrial clustering.
99	mildly decreases gtpase activity.
102	impairs protein folding. decreases gtpase activity.
107	loss of function in mitochondrial fusion. abolishes gtpase activity, but has no effect on gtp binding.
109	acts as a dominant negative mutant; induces fragmentation of mitochondria.
144	abolishes gtpase activity. abolishes dimerization.
173	decreases gtpase activity.
189	causes mitochondrial clumping.
209	abolishes dimerization. loss of function in mitochondrial fusion. abolishes gtpase activity, but has no effect on gtp bi
238	abolishes dimerization. loss of function in mitochondrial fusion. abolishes gtpase activity, but has no effect on gtp bi
239	abolishes gtp binding and gtpase activity. loss of function in mitochondrial fusion.
245	decreases gtpase activity. abolishes dimerization. impairs mitochondrial fusion.
309	mildly decreases gtpase activity and impairs mitochondrial fusion.
328	slightly decreases gtpase activity.
336	loss of function in mitochondrial fusion. abolishes dimerization. decreases gtpase activity.
336	decreases gtpase activity and impairs mitochondrial fusion.
705	impairs protein folding. decreases gtpase activity.
733	impairs protein folding.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-5205685	PINK1-PRKN Mediated Mitophagy
R-HSA-9013419	RHOT2 GTPase cycle
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis
R-HSA-162582	Signal Transduction
R-HSA-1632852	Macroautophagy
R-HSA-5205647	Mitophagy
R-HSA-9612973	Autophagy
R-HSA-9663891	Selective autophagy
R-HSA-9715370	Miro GTPase Cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 197 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_MSH3, CMYB_01, MORF_BRCA1, MORF_ATRX, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, MORF_ESR1, CTATGCA_MIR153, chr3q26, MORF_RAD51L3, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS

GO Biological Process (5): mitochondrial fusion (GO:0008053), positive regulation of mitochondrial membrane potential (GO:0010918), GTP metabolic process (GO:0046039), mitochondrion localization (GO:0051646), mitochondrion organization (GO:0007005)

GO Molecular Function (6): GTPase activity (GO:0003924), GTP binding (GO:0005525), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020), outer mitochondrial membrane protein complex (GO:0098799), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Mitophagy	1
Miro GTPase Cycle	1
Hemostasis	1
Autophagy	1
Selective autophagy	1
Macroautophagy	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
mitochondrion organization	1
organelle fusion	1
positive regulation of membrane potential	1
regulation of mitochondrial membrane potential	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
organelle localization	1
organelle organization	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
mitochondrial outer membrane	1
membrane protein complex	1
mitochondrial protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFN1	OPA1	O60313	984
MFN1	MFN2	O95140	983
MFN1	RHOT1	Q8IXI2	961
MFN1	DNM1L	O00429	938
MFN1	PINK1	Q9BXM7	930
MFN1	FIS1	Q9Y3D6	929
MFN1	MFF	Q9GZY8	925
MFN1	RHOT2	Q8IXI1	923
MFN1	PHB2	Q99623	903
MFN1	GDAP1	Q8TB36	884
MFN1	PRKN	O60260	871
MFN1	VDAC1	P21796	860
MFN1	CYCS	P00001	825
MFN1	MARCHF5	Q9NX47	816
MFN1	MIEF2	Q96C03	810

IntAct

45 interactions, top by confidence:

A	B	Type	Score
MFN1	MFN2	psi-mi:“MI:0915”(physical association)	0.790
MFN1	MFN2	psi-mi:“MI:0914”(association)	0.790
MFN2	MFN1	psi-mi:“MI:0915”(physical association)	0.790
FAF2	UBB	psi-mi:“MI:0914”(association)	0.640
TOMM22	XRCC3	psi-mi:“MI:0914”(association)	0.640
MFN1	MFN1	psi-mi:“MI:0407”(direct interaction)	0.620
BAK1	MFN2	psi-mi:“MI:0914”(association)	0.530
MAVS	MFN1	psi-mi:“MI:0915”(physical association)	0.400
MFN1	MAVS	psi-mi:“MI:0915”(physical association)	0.400
Bak1	MFN1	psi-mi:“MI:0915”(physical association)	0.400
PLK2	C1orf226	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
PSMC6	PSMD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (91): MFN1 (Affinity Capture-MS), MFN1 (Affinity Capture-MS), MFN1 (Affinity Capture-MS), SLC25A38 (Affinity Capture-Western), MFN1 (Affinity Capture-Western), MFN2 (Affinity Capture-MS), MFN1 (Affinity Capture-MS), MFN1 (Affinity Capture-MS), FLNC (Affinity Capture-MS), MFN1 (Affinity Capture-Western), MGRN1 (Affinity Capture-Western), MFN1 (Affinity Capture-Western), MFN1 (Affinity Capture-Western), MFN1 (Affinity Capture-Western), MFN1 (Co-fractionation)

ESM2 similar proteins: A6H8H2, A8E7G4, A8XSV3, B2RY04, B4IB36, B4QL99, E9PXF8, P29742, P34574, P50748, P53675, Q08BC6, Q0II26, Q14185, Q19317, Q29NZ8, Q55FE3, Q5EA76, Q5F3R2, Q5U4T8, Q5VZ89, Q5XH29, Q66HC3, Q66KD9, Q6DF78, Q6DFW0, Q6IQX0, Q6NRQ2, Q6NSW5, Q6NTN5, Q6PA97, Q7YTB0, Q7Z401, Q80Y84, Q811U4, Q86WG5, Q8BUR4, Q8C3Y4, Q8IWA4, Q8LPU4

Diamond homologs: O18412, O95140, Q7YU24, Q80U63, Q811U4, Q8IWA4, Q8R4Z9, Q8R500, Q9N6P4, Q23424

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
PRKN	“down-regulates quantity”	MFN1	ubiquitination
MARCHF5	“down-regulates quantity by destabilization”	MFN1	ubiquitination
MFN1	up-regulates	Mitochondrial_fusion
PINK1	“down-regulates quantity”	MFN1	ubiquitination
ERK1/2	“up-regulates activity”	MFN1	phosphorylation
AMFR	“down-regulates quantity by destabilization”	MFN1	polyubiquitination
PRKCB	“down-regulates activity”	MFN1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

110 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3413 predictions. Top by Δscore:

Variant	Effect	Δscore
3:179347944:A:T	donor_gain	1.0000
3:179348843:A:AG	acceptor_gain	1.0000
3:179348844:G:GG	acceptor_gain	1.0000
3:179348844:GTAGC:G	acceptor_gain	1.0000
3:179348960:GAAGG:G	donor_loss	1.0000
3:179348961:AAGG:A	donor_loss	1.0000
3:179348962:AGGTT:A	donor_loss	1.0000
3:179348964:GTTA:G	donor_loss	1.0000
3:179351879:A:AG	acceptor_gain	1.0000
3:179351879:AAT:A	acceptor_gain	1.0000
3:179351890:A:AG	acceptor_gain	1.0000
3:179351891:A:G	acceptor_gain	1.0000
3:179351892:T:G	acceptor_gain	1.0000
3:179351895:T:A	acceptor_gain	1.0000
3:179351895:TGCAG:T	acceptor_gain	1.0000
3:179351896:GCA:G	acceptor_loss	1.0000
3:179351896:GCAGC:G	acceptor_gain	1.0000
3:179351897:CAGC:C	acceptor_loss	1.0000
3:179351897:CAGCA:C	acceptor_gain	1.0000
3:179351898:A:AG	acceptor_gain	1.0000
3:179351898:A:G	acceptor_loss	1.0000
3:179351898:AGCAA:A	acceptor_gain	1.0000
3:179351899:G:GA	acceptor_gain	1.0000
3:179351899:GC:G	acceptor_gain	1.0000
3:179351899:GCA:G	acceptor_gain	1.0000
3:179351899:GCAA:G	acceptor_gain	1.0000
3:179351899:GCAAC:G	acceptor_gain	1.0000
3:179352020:T:TA	donor_gain	1.0000
3:179352021:G:GA	donor_gain	1.0000
3:179352033:CAGGT:C	donor_loss	1.0000

AlphaMissense

4902 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:179364368:T:A	V203D	0.999
3:179375253:T:C	F337L	0.999
3:179375255:C:A	F337L	0.999
3:179375255:C:G	F337L	0.999
3:179348882:T:C	F11L	0.998
3:179348884:T:A	F11L	0.998
3:179348884:T:G	F11L	0.998
3:179348892:C:A	A14D	0.998
3:179348896:G:C	K15N	0.998
3:179348896:G:T	K15N	0.998
3:179364358:G:C	D200H	0.998
3:179364358:G:T	D200Y	0.998
3:179364359:A:G	D200G	0.998
3:179364359:A:T	D200V	0.998
3:179375254:T:C	F337S	0.998
3:179358935:T:A	V115D	0.997
3:179364355:G:C	A199P	0.997
3:179364359:A:C	D200A	0.997
3:179365170:T:C	F233S	0.997
3:179365187:T:A	W239R	0.997
3:179365187:T:C	W239R	0.997
3:179375262:C:G	H340D	0.997
3:179375274:G:C	A344P	0.997
3:179375275:C:A	A344D	0.997
3:179352005:G:C	R73P	0.996
3:179364360:T:A	D200E	0.996
3:179364360:T:G	D200E	0.996
3:179365173:T:A	I234N	0.996
3:179365176:T:A	L235H	0.996
3:179365176:T:C	L235P	0.996

dbSNP variants (sampled 300 via entrez): RS1000030520 (3:179350475 A>G), RS1000046357 (3:179357220 T>A), RS1000080119 (3:179356993 A>G), RS1000090840 (3:179356900 C>T), RS1000127519 (3:179375852 G>A), RS1000251083 (3:179351000 T>G), RS1000280089 (3:179375712 A>G), RS1000302710 (3:179393815 A>G), RS1000471936 (3:179369304 T>A), RS1000485094 (3:179387410 G>A,C), RS1000500303 (3:179380144 T>G), RS1000505225 (3:179388241 C>A), RS1000531165 (3:179380531 G>T), RS1000556483 (3:179346348 C>T), RS1000601717 (3:179350707 G>A)

Disease associations

OMIM: gene MIM:608506 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007059_17	Response to antidepressants (symptom improvement)	3.000000e-06
GCST010273_7	Gout (normal type)	5.000000e-07
GCST90002400_409	Plateletcrit	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Mitofusin proteins

CTD chemical–gene interactions

88 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Hydrogen Peroxide	affects cotreatment, affects reaction, decreases expression, decreases reaction, increases expression	3
bisphenol A	decreases expression, increases methylation, decreases reaction	2
perfluorooctanoic acid	increases expression	2
epigallocatechin gallate	affects cotreatment, affects reaction, decreases expression, decreases reaction	2
Resveratrol	affects cotreatment, increases expression	2
Acetylcysteine	increases degradation, decreases expression, affects cotreatment, decreases reaction	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Melatonin	decreases expression, decreases reaction, increases expression	2
Thapsigargin	decreases expression, increases reaction, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases methylation	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
trichostatin A	affects expression	1
hydroxyhydroquinone	decreases expression	1
mono-(2-ethylhexyl)phthalate	affects cotreatment, decreases reaction, increases degradation, increases reaction	1
sodium arsenite	increases expression	1
butyraldehyde	increases methylation	1
didecyldimethylammonium	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
caprylic aldehyde	increases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
caffeic acid	decreases expression, increases reaction	1
pentanal	increases methylation	1
heptanal	increases methylation	1
gallocatechol	affects cotreatment, affects reaction, decreases expression, decreases reaction	1
epicatechin gallate	affects cotreatment, affects reaction, decreases expression, decreases reaction	1
sarpogrelate	decreases expression, decreases reaction, increases reaction	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D9K7	Ubigene HEK293 MFN1 KO	Transformed cell line	Female
CVCL_SY18	HAP1 MFN1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.