MFN2

Summary

MFN2 (mitofusin 2, HGNC:16877) is a protein-coding gene on chromosome 1p36.22, encoding Mitofusin-2 (O95140). Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion. It is a selective cancer dependency (DepMap: 76.8% of cell lines).

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.

Source: NCBI Gene 9927 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multiple symmetric lipomatosis with partial lipodystrophy (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 1,448 total — 97 pathogenic, 86 likely-pathogenic (top 2% of genes corpus-wide)
• GTEx eGene: eQTL in 38 tissues, sQTL in 34 (q < 0.05)
• Phenotypes (HPO): 111
• Cancer dependency (DepMap): dependent in 76.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.60 (unconstrained)
• MANE Select transcript: NM_014874
• Interaction hub: 2,859 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16877
Approved symbol	MFN2
Name	mitofusin 2
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	CPRP1, KIAA0214, MARF, CMT2A2
Ensembl gene	ENSG00000116688
Ensembl biotype	protein_coding
OMIM	608507
Entrez	9927

Gene structure

Transcript identifiers

Ensembl transcripts: 81 — 64 protein_coding, 6 protein_coding_CDS_not_defined, 6 retained_intron, 5 nonsense_mediated_decay

MANE Select: ENST00000235329

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 2

ENST00000235329, ENST00000412236, ENST00000444836, ENST00000484391, ENST00000490079, ENST00000497302, ENST00000674548, ENST00000674658, ENST00000674706, ENST00000674817, ENST00000674910, ENST00000675043, ENST00000675053, ENST00000675113, ENST00000675194, ENST00000675231, ENST00000675298, ENST00000675374, ENST00000675404, ENST00000675483, ENST00000675512, ENST00000675528, ENST00000675530, ENST00000675781, ENST00000675817, ENST00000675872, ENST00000675919, ENST00000675959, ENST00000675987, ENST00000676293, ENST00000676295, ENST00000676369, ENST00000676426, ENST00000898883, ENST00000898884, ENST00000898885, ENST00000898886, ENST00000898887, ENST00000898888, ENST00000898889, ENST00000898890, ENST00000898891, ENST00000898892, ENST00000898893, ENST00000898894, ENST00000898895, ENST00000898896, ENST00000898897, ENST00000898898, ENST00000898899, ENST00000898900, ENST00000917332, ENST00000967393, ENST00000967394, ENST00000967395, ENST00000967396, ENST00000967397, ENST00000967398, ENST00000967399, ENST00000967400, ENST00000967401, ENST00000967402, ENST00000967403, ENST00000967404, ENST00000967405, ENST00000967406, ENST00000967407, ENST00000967408, ENST00000967409, ENST00000967410, ENST00000967411, ENST00000967412, ENST00000967413, ENST00000967414, ENST00000967415, ENST00000967416, ENST00000967417, ENST00000967418, ENST00000967419, ENST00001079745, ENST00001144325

RefSeq mRNA: 2 — MANE Select: NM_014874 NM_001127660, NM_014874

CCDS: CCDS30587

Canonical transcript exons

ENST00000235329 — 19 exons

Exon	Start	End
ENSE00001336968	11981970	11982114
ENSE00001336972	11980444	11980484
ENSE00001618211	12004509	12004613
ENSE00001654095	12004825	12004927
ENSE00001665725	11997297	11997421
ENSE00001674753	12001769	12001836
ENSE00001684279	12001401	12001554
ENSE00001684472	12007053	12007249
ENSE00001698937	11998988	11999095
ENSE00001702003	12006538	12006693
ENSE00001719147	11998770	11998878
ENSE00001770250	11996156	11996318
ENSE00001771463	12005711	12005931
ENSE00001777072	12001982	12002103
ENSE00001785284	12009592	12009726
ENSE00001785362	12003992	12004118
ENSE00001851384	12011496	12013508
ENSE00002228720	11992555	11992690
ENSE00003686591	11989165	11989343

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.4709 / max 330.0526, expressed in 1820 samples.

Highest expression (Bgee): apex of heart, heart left ventricle, cardiac ventricle, hindlimb stylopod muscle, atrium auricular region.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MFN2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 38 tissues and its splicing (sQTL) in 34 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 72 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	3.2e-159	-0.65	1:11986032:G:A
Testis	eqtl	1.5e-81	-0.75	1:11982386:C:T
Cells Cultured fibroblasts	eqtl	1.8e-52	-0.20	1:11986032:G:A
Muscle Skeletal	sqtl	2.9e-35	+0.65	1:11979234:G:GAC
Esophagus Mucosa	eqtl	4.8e-31	-0.29	1:11982204:A:G
Spleen	eqtl	5.3e-31	-0.43	1:11986032:G:A
Lung	eqtl	1.6e-30	-0.27	1:12008468:A:G
Adipose Subcutaneous	eqtl	4.2e-25	-0.20	1:11986032:G:A
Brain Hippocampus	eqtl	1.0e-17	+0.32	1:11980146:A:G
Skin Sun Exposed Lower leg	eqtl	1.1e-17	-0.15	1:12013880:G:A
Artery Tibial	sqtl	1.1e-17	+0.52	1:11982204:A:G
Esophagus Muscularis	sqtl	1.9e-16	+0.60	1:11973851:G:A
Adipose Visceral Omentum	eqtl	1.5e-15	-0.17	1:11999355:C:T
Skin Not Sun Exposed Suprapubic	eqtl	3.9e-15	-0.19	1:11993043:C:T
Brain Putamen basal ganglia	eqtl	2.5e-14	+0.36	1:11980267:A:G
Colon Transverse	eqtl	4.1e-14	-0.16	1:12008884:T:C
Skin Sun Exposed Lower leg	sqtl	1.8e-12	+0.45	1:11982386:C:T
Muscle Skeletal	eqtl	1.0e-11	-0.11	1:12011623:A:G
Brain Cerebellar Hemisphere	sqtl	1.3e-11	+0.77	1:11982204:A:G
Cells Cultured fibroblasts	sqtl	2.2e-11	+0.38	1:11982204:A:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
668	41.4417	1820
669	1.4100	802
667	0.4523	203
670	0.0742	23
673	0.0629	20
201354	0.0297	4

Top tissues by expression

showing 100 of 300 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.20	gold quality
heart left ventricle	UBERON:0002084	98.93	gold quality
cardiac ventricle	UBERON:0002082	98.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.63	gold quality
right atrium auricular region	UBERON:0006631	98.62	gold quality
cardiac atrium	UBERON:0002081	98.58	gold quality
gastrocnemius	UBERON:0001388	98.53	gold quality
muscle of leg	UBERON:0001383	98.38	gold quality
left ventricle myocardium	UBERON:0006566	98.20	gold quality
heart	UBERON:0000948	98.15	gold quality
muscle organ	UBERON:0001630	97.95	gold quality
skeletal muscle organ	UBERON:0014892	97.95	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.88	gold quality
lower esophagus	UBERON:0013473	97.80	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.80	gold quality
cranial nerve II	UBERON:0000941	97.66	gold quality
myocardium	UBERON:0002349	97.59	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.27	gold quality
diaphragm	UBERON:0001103	97.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.23	gold quality
skeletal muscle tissue	UBERON:0001134	97.21	gold quality
heart right ventricle	UBERON:0002080	97.19	gold quality
muscle tissue	UBERON:0002385	97.16	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.93	gold quality
body of tongue	UBERON:0011876	96.89	gold quality
skin of leg	UBERON:0001511	96.88	gold quality
vastus lateralis	UBERON:0001379	96.79	gold quality
esophagus	UBERON:0001043	96.75	gold quality
prefrontal cortex	UBERON:0000451	96.74	gold quality
quadriceps femoris	UBERON:0001377	96.67	gold quality
skin of abdomen	UBERON:0001416	96.67	gold quality
deltoid	UBERON:0001476	96.62	gold quality
right frontal lobe	UBERON:0002810	96.58	gold quality
putamen	UBERON:0001874	96.57	gold quality
tongue squamous epithelium	UBERON:0006919	96.56	gold quality
nucleus accumbens	UBERON:0001882	96.38	gold quality
amygdala	UBERON:0001876	96.37	gold quality
triceps brachii	UBERON:0001509	96.34	gold quality
gluteal muscle	UBERON:0002000	96.27	gold quality
cingulate cortex	UBERON:0003027	96.26	gold quality
anterior cingulate cortex	UBERON:0009835	96.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.19	gold quality
mucosa of stomach	UBERON:0001199	96.18	gold quality
hypothalamus	UBERON:0001898	96.10	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.10	gold quality
caudate nucleus	UBERON:0001873	96.08	gold quality
superior vestibular nucleus	UBERON:0007227	96.04	gold quality
lower esophagus mucosa	UBERON:0035834	95.98	gold quality
biceps brachii	UBERON:0001507	95.96	gold quality
ventral tegmental area	UBERON:0002691	95.92	gold quality
saphenous vein	UBERON:0007318	95.90	gold quality
esophagus mucosa	UBERON:0002469	95.88	gold quality
inferior vagus X ganglion	UBERON:0005363	95.88	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.88	gold quality
substantia nigra	UBERON:0002038	95.85	gold quality
left lobe of thyroid gland	UBERON:0001120	95.83	gold quality
tongue	UBERON:0001723	95.83	gold quality
tibialis anterior	UBERON:0001385	95.82	gold quality
midbrain	UBERON:0001891	95.82	gold quality
nipple	UBERON:0002030	95.81	gold quality
spinal cord	UBERON:0002240	95.81	gold quality
transverse colon	UBERON:0001157	95.78	gold quality
zone of skin	UBERON:0000014	95.77	gold quality
frontal cortex	UBERON:0001870	95.70	gold quality
frontal lobe	UBERON:0016525	95.70	gold quality
right lobe of thyroid gland	UBERON:0001119	95.68	gold quality
middle frontal gyrus	UBERON:0002702	95.58	gold quality
fundus of stomach	UBERON:0001160	95.57	gold quality
neocortex	UBERON:0001950	95.57	gold quality
body of stomach	UBERON:0001161	95.55	gold quality
vena cava	UBERON:0004087	95.51	gold quality
thyroid gland	UBERON:0002046	95.50	gold quality
dorsal plus ventral thalamus	UBERON:0001897	95.48	gold quality
frontal pole	UBERON:0002795	95.47	gold quality
mucosa of transverse colon	UBERON:0004991	95.43	gold quality
right lobe of liver	UBERON:0001114	95.42	gold quality
telencephalon	UBERON:0001893	95.40	gold quality
cerebellar cortex	UBERON:0002129	95.40	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.40	gold quality
cerebellar hemisphere	UBERON:0002245	95.38	gold quality
upper arm skin	UBERON:0004263	95.37	gold quality
sigmoid colon	UBERON:0001159	95.34	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.32	gold quality
forebrain	UBERON:0001890	95.27	gold quality
pharyngeal mucosa	UBERON:0000355	95.24	gold quality
central nervous system	UBERON:0001017	95.23	gold quality
medial globus pallidus	UBERON:0002477	95.22	gold quality
brain	UBERON:0000955	95.21	gold quality
stomach	UBERON:0000945	95.19	gold quality
globus pallidus	UBERON:0001875	95.11	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.11	gold quality
cerebral cortex	UBERON:0000956	95.08	gold quality
cerebellum	UBERON:0002037	95.07	gold quality
colon	UBERON:0001155	95.05	gold quality
medulla oblongata	UBERON:0001896	95.02	gold quality
small intestine	UBERON:0002108	94.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.88	gold quality
cardia of stomach	UBERON:0001162	94.86	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	1486.02
E-MTAB-2983	no	13.36
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	315.0
Skeletal muscle	tissue	290.9	medium
Heart muscle	tissue	253.1	medium
Caudate putamen	tissue	103.2
Frontal cortex	tissue	100.9
Locus coeruleus	tissue	94.8
Nucleus accumbens	tissue	74.6
Postcentral gyrus	tissue	72.7
Parathyroid gland	tissue	72.0	not detected
Hippocampus	tissue	70.7	medium
Seminal vesicle	tissue	58.7	medium
Thalamus	tissue	55.1
Pons	tissue	54.1
Esophagus	tissue	53.3	medium
Midbrain	tissue	52.6
Thyroid gland	tissue	52.6	medium
Spinal cord	tissue	51.7
Superior colliculi	tissue	51.1
Medulla oblongata	tissue	50.3
Substantia nigra	tissue	50.2
Putamen	tissue	48.2
Cerebral cortex	tissue	46.2	high
Somatosensory cortex	tissue	46.2
Motor cortex	tissue	45.4
Corpus callosum	tissue	45.0
Choroid plexus	tissue	44.4
Ventral forebrain	tissue	44.4
Hypothalamus	tissue	44.2
Prefrontal cortex	tissue	43.9
Small intestine	tissue	43.6	high
Hippocampal formation	tissue	43.4
Basal ganglia	tissue	42.6	medium
Occipital cortex	tissue	42.3
Periaqueductal gray	tissue	41.4
Retrosplenial and cingulate cortex	tissue	40.7
Septum	tissue	40.4
Urinary bladder	tissue	39.9	medium
Liver	tissue	39.9	not detected
Duodenum	tissue	39.5	high
Retrosplenial cortex	tissue	39.5
Entorhinal cortex	tissue	39.2
Insular cortex	tissue	38.9
Smooth muscle	tissue	38.5	low
Temporal cortex	tissue	38.3
Colon	tissue	36.3	medium
Rectum	tissue	35.8	medium
Amygdala	tissue	35.4
Skin 1	tissue	35.1	low
Prostate	tissue	34.1	medium
Kidney	tissue	34.0	high
Adipose tissue	tissue	32.6	low
Retina	tissue	32.5
Olfactory bulb	tissue	30.1
Stomach 1	tissue	28.5	medium
Tonsil	tissue	28.5	high
Cerebellum	tissue	28.1	high
Salivary gland	tissue	27.6	low
Placenta	tissue	26.0	high
Lung	tissue	26.0	low
Bone marrow	tissue	25.6	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Posterior thalamic nucleus (113.2), Cervical spinal cord, ventral horn (101.6), Lateral geniculate body (98.9), Mammillary body (98.4), Globus pallidus, externus (96.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESRRA, KLF4, PPARD, PPARG, PPARGC1A, SP1, STOML2, TP53

miRNA regulators (miRDB)

Targeting MFN2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 79 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527

Functional genomics

gnomAD constraint: pLI 0.000565, LOEUF 0.602, missense Z 3.23 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000235329 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:11,989,169–11,989,229	31 / 23.2	1.33	no
1:11,989,230–11,999,014	141 / 278.9	0.51	no
1:11,999,015–12,011,562	571 / 670.7	0.85	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map
DepMap (CRISPR cell-line fitness): dependent in 76.8% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SU-DHL-10 (-1.884), TOV-112D (-1.821), RERF-LC-Sq1 (-1.533), OCI-AML2 (-1.428), PANC-1 (-1.402), Caov-4 (-1.291), SF-295 (-1.283), NCI-H1944 (-1.277), OCI-AML3 (-1.262), KE-39 (-1.256), MHH-ES-1 (-1.25), TALL-1 (-1.248), HCC1143 (-1.24), PA-TU-8988S (-1.234), SNU-620 (-1.234).

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)
• Drp1 and Mfn2, but not other proteins implicated in the regulation of mitochondrial morphology, colocalize with Bax in apoptotic foci (PMID:12499352)
• Mfn2-dependent mechanism of mitochondrial control is disturbed in obesity by reduced Mfn2 expression (PMID:12598526)
• Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A (PMID:15064763)
• Review. Mitofusin-2 stimulates mitochondrial substrate oxidation, respiration & membrane potential.It may play an important role in energy balance. Its expression is repressed in obese skeletal muscle suggesting a posible role in obesity. (PMID:15382611)
• Mfn2 triggers mitochondrial energization, at least in part, by regulating OXPHOS expression through signals that are independent of its role as a mitochondrial fusion protein (PMID:15829499)
• Mfn2 is a signaling GTPase regulating mitochondrial fusion; the nucleotide-dependent activation of Mfn2 concomitantly protects the organelle from permeability transition (PMID:15878861)
• Mfn1, Mfn2, NRF-2 and COX IV mRNA were increased 24 h post-exercise in skeletal muscle (PMID:15961417)
• Given the frequency of MFN2 mutations among CMT2 probands (3/13, or 23%), genetic testing of CMT2 patients should begin with a screen of the MFN2 gene. (PMID:16043786)
• HSG plays an essential role in mouse preimplantation development (PMID:16083859)
• Type 2 Charcot Marie Tooth Disease is genetically heterogeneous. It may or may not be caused by mutations in the MFN2 gene. (PMID:16087932)
• A study evaluating Mfn2 expression in skeletal muscle from obese or nonobese type 2 diabetic subjects in response to body weight, and the role of TNF-alpha and IL-6 in its regulation is reported. (PMID:16123358)
• the significant increase in mitofusin 2 mRNA levels may explain the increase in glucose oxidation observed in morbid obesity (PMID:16160866)
• This study identified a unique mutation in the gene mitofusin 2 (MFN2). In three families, the MFN2 mutation occurred de novo; in two families the mutation was subsequently transmitted from father to son indicating autosomal dominant inheritance. (PMID:16437557)
• A significant role of mutations in MFN2 in the pathogenesis of Charcot-Marie-Tooth disease type 2. (PMID:16762064)
• Charcot-Marie-Tooth disease-associated MFN2 mutant proteins induce abnormal clustering of small fragmented mitochondria in both neuronal cell bodies and proximal axons. Transport of these mitochondria in axons is significantly impaired. (PMID:17215403)
• findings suggest that mutations in the MFN2 gene are an important causative gene underlying Korean patients with Charcot-Marie-Tooth neuropathy type 2 (PMID:17309650)
• We also suggest that single patients with early-onset axonal polyneuropathies should be screened for MFN2 mutations. (PMID:17437620)
• a signaling role for Mfn2 in the regulation of apoptosis that extends beyond its role in mitochondrial fusion (PMID:17537722)
• Mitofusin-2 gene can inhibit the proliferation of MCF-7 cells and increase their chemosensitivity to camptothecin. (PMID:17697539)
• 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)
• Weight loss upregulates the peroxisome proliferator-activated receptor gamma coactivator gene, which in turn stimulates mitofusin-2 expression, which contributes to the improvement of insulin sensitivity. (PMID:17828388)
• MFN2 gene mutations were shown to be the most common cause of autosomal dominant hereditary axonopathy. In addition, MFN2 gene mutations were also identified in CMT type 6 (axonal neuropathy with optic nerve atrophy). (PMID:17874344)
• study reports a novel MFN2 mutation shared by two apparently unrelated Charcot-Marie-Tooth families originating from the same area in Southern Italy (PMID:17940179)
• observations are in agreement with the neuronal specificity of the disease and are consistent with a recent finding that mitochondrial fusion can be maintained in cells that express mutant Mfn2 protein due to complementation by a second mitofusin, Mfn1. (PMID:18316077)
• Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations. (PMID:18425620)
• Severe early-onset axonal neuropathy due to MFN2 mutations can present as an apparently recessively inherited neuropathy but the minimal phenotype in the parents suggests a semi-dominant mechanism. (PMID:18458227)
• mitofusin-2 may have a role in inhibiting the proliferation of MCF-7 cells and promoting their sensitivity to camptothecin with a synergic effect (PMID:18480994)
• early onset stroke without peripheral neuropathy caused by mutation in MFN2 (PMID:18490623)
• Cognitive impairment may be another feature of the MFN2-related phenotype. The widespread peripheral and CNS involvement, as well as the neurosensorial defects, underline the similarities among MFN2-related and primary mitochondrial disorders. (PMID:18946002)
• Neurophysiologic findings were most suggestive of axonal degeneration, but some onion bulbs were present in all mitofusin 2 mutations cases. Axonal mitochondria were smaller than normal, were round, and were abnormally aggregated. (PMID:18957892)
• A novel role of PGC-1beta in mitochondrial physiology, namely the control of mitochondrial fusion mainly through Mfn2. (PMID:18974884)
• mitofusin 2 tethers ER to mitochondria, a juxtaposition required for efficient mitochondrial Ca(2+) uptake (PMID:19052620)
• 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 blocked the dissociation of Bak from Mfn2. (PMID:19168699)
• a role of mutant Mfn2 in neuronal function and physiopathology of Charcot-Marie-Tooth disease type 2A (Review) (PMID:19427854)
• MFN2 plays a role in controlling ATP/ADP exchanges in Charcot-Marie-Tooth type 2A disease (PMID:19618221)
• Data revealed that Mfn2 interacted with the carboxyl-terminal region of MAVS through a heptad repeat region, providing a structural perspective on the regulation of the mitochondrial antiviral response. (PMID:19690333)
• Results identify diverse effects of CMT2A mutations, including a possible role for Mfn2 ubiquitylation and degradation in CMT2A pathogenesis, and provide evidence for a link between Fzo1 GTP hydrolysis, ubiquitylation, and mitochondrial fusion. (PMID:19812251)
• Study found twenty-four Charcot-Marie-Tooth (CMT) disease patients from 14 different families were identified with nine different MFN2 mutations. (PMID:19889647)
• Mitofusin 2 mutations are a frequent cause of Charcot-Marie-Tooth disease type 2, with variable severity and either dominant or recessive inheritance. (PMID:20008656)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfn2	ENSDARG00000079504
mus_musculus	Mfn2	ENSMUSG00000029020
rattus_norvegicus	Mfn2	ENSRNOG00000046424
drosophila_melanogaster	fzo	FBGN0011596
drosophila_melanogaster	Marf	FBGN0029870
caenorhabditis_elegans		WBGENE00001509

Paralogs (1): MFN1 (ENSG00000171109)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2442230) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 89 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal mitochondrial morphology	7
abnormal gait	3
small testis	2
small seminiferous tubules	2
decreased body weight	2
abnormal mitochondrial physiology	2
abnormal respiratory electron transport chain	2
abnormal myocardial fiber morphology	1
abnormal hindlimb morphology	1
abnormal autopod morphology	1
kinked tail	1
short tail	1
muscle weakness	1
abnormal cerebellum morphology	1
small cerebellum	1
Purkinje cell degeneration	1
abnormal motor neuron morphology	1
seminiferous tubule degeneration	1
abnormal spermatogenesis	1
weight loss	1
decreased body size	1
decreased locomotor activity	1
impaired coordination	1
impaired righting response	1
impaired limb coordination	1

+64 more (showing top 25).

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PLOD1	protein-coding	5351
MIIP	protein-coding	60672
TNFRSF8	protein-coding	943
MIR6729	ncRNA	102466982
KIAA2013	protein-coding	90231

Protein

Protein identifiers

Mitofusin-2 — O95140 (reviewed: O95140)

Alternative names: Transmembrane GTPase MFN2

All UniProt accessions (9): A0A6Q8PFJ4, A0A6Q8PFT5, A0A6Q8PGA3, A0A6Q8PGR2, A0A6Q8PGS9, A0A6Q8PGV8, A0A6Q8PH07, O95140, Q5JXC5

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion. 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. Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains. Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes. Plays an important role in the regulation of vascular smooth muscle cell proliferation. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy). Is required for PRKN recruitment to dysfunctional mitochondria. Involved in the control of unfolded protein response (UPR) upon ER stress including activation of apoptosis and autophagy during ER stress. Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions.

Subunit / interactions. Forms homomultimers and heteromultimers with MFN1. Oligomerization is essential for mitochondrion fusion. Interacts with VAT1. Interacts with STOML2; may form heterooligomers. Interacts (phosphorylated) with PRKN. Interacts with EIF2AK3. Interacts with THG1L; THG1L probably functions as a guanyl-nucleotide exchange factor/GEF, activating MFN2. Interacts with TRABD.

Subcellular location. Mitochondrion outer membrane.

Tissue specificity. Ubiquitous; expressed at low level. Highly expressed in heart and kidney.

Post-translational modifications. Phosphorylated by PINK1. Ubiquitinated by non-degradative ubiquitin by PRKN, promoting mitochondrial fusion; deubiquitination by USP30 inhibits mitochondrial fusion. Ubiquitinated by HUWE1 when dietary stearate (C18:0) levels are low; ubiquitination inhibits mitochondrial fusion.

Disease relevance. Charcot-Marie-Tooth disease, axonal, type 2A2B (CMT2A2B) [MIM:617087] An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2A2B is a severe form with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, axonal, type 2A2A (CMT2A2A) [MIM:609260] An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. The disease is caused by variants affecting the gene represented in this entry. Neuropathy, hereditary motor and sensory, 6A, with optic atrophy (HMSN6A) [MIM:601152] An autosomal dominant neurologic disorder characterized by optic atrophy and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. It is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Peripheral axonal neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, and normal or slightly reduced nerve conduction velocities. The disease is caused by variants affecting the gene represented in this entry. Lipomatosis, multiple symmetric, with or without peripheral neuropathy (MSL) [MIM:151800] An autosomal recessive disorder characterized by the growth of unencapsulated, lipomatous masses affecting the upper body, especially the cervical and thoracic regions. Lipomatosis can be disfiguring, and lipoma growth around the neck may cause difficulty swallowing or breathing. The age at onset ranges from childhood to young adulthood. Some patients develop distal muscle weakness and atrophy due to axonal peripheral neuropathy. The disease is caused by variants affecting the gene represented in this entry.

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.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O95140-1	1	yes
O95140-2	2

RefSeq proteins (2): NP_001121132, NP_055689* (*=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)

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

UniProt features (132 total): sequence variant 56, helix 21, mutagenesis site 15, strand 10, region of interest 8, binding site 4, topological domain 3, turn 3, splice variant 3, coiled-coil region 2, transmembrane region 2, modified residue 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
6JFK	GDP bound Mitofusin2 (MFN2)	X-RAY DIFFRACTION	2
6JFM	Mitofusin2 (MFN2)_T111D	X-RAY DIFFRACTION	2.09
6JFL	Nucleotide-free Mitofusin2 (MFN2)	X-RAY DIFFRACTION	2.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95140-F1	81.94	0.44

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH uncertain · IF supported

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)

Position	Role
106–111	GTP
258–261	GTP
305	GTP
307	GTP

Post-translational modifications (2)

Type	Positions
Phosphothreonine	111
Phosphoserine	442

Mutagenesis-validated functional residues (15)

Position	Phenotype
109	does not affect its ability to cluster mitochondria; when overexpressed.
110	does not affect its ability to cluster mitochondria; when overexpressed.
111	diminishes interaction with prkn in presence of pink1. abolishes phosphorylation by pink1 and interaction with prkn in presence of pink1 …
111	interacts with prkn in absence of pink1; when associated with glu-442.
128	loss of function in promoting mitochondrial fusion.
230	loss of function in promoting mitochondrial fusion.
259	loss of function in promoting mitochondrial fusion.
259	does not affect its ability to cluster mitochondria; when overexpressed.
260	loss of function in promoting mitochondrial fusion.
266	loss of function in promoting mitochondrial fusion.
442	diminishes interaction with prkn in presence of pink1. abolishes phosphorylation by pink1 and interaction with prkn in presence of pink1 …
442	interacts with prkn in absence of pink1; when associated with glu-111.
622–624	does not affect the targeting to mitochondrial outer membrane.
622–624	abolishes the targeting to mitochondrial outer membrane.
657–659	does not affect the targeting to mitochondrial outer membrane.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

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

MSigDB gene sets: 448 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_VACUOLE_ORGANIZATION, DITTMER_PTHLH_TARGETS_UP, GOBP_PROTEIN_TARGETING, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_BLASTOCYST_FORMATION, GOBP_MUSCLE_CELL_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_MACROAUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, MORF_RAF1, GOBP_ANIMAL_ORGAN_MORPHOGENESIS

GO Biological Process (15): apoptotic process (GO:0006915), response to unfolded protein (GO:0006986), mitochondrial membrane organization (GO:0007006), mitochondrial fusion (GO:0008053), aerobic respiration (GO:0009060), protein localization to phagophore assembly site (GO:0034497), negative regulation of Ras protein signal transduction (GO:0046580), negative regulation of smooth muscle cell proliferation (GO:0048662), mitochondrion localization (GO:0051646), type 2 mitophagy (GO:0061734), positive regulation of cold-induced thermogenesis (GO:0120162), positive regulation of vascular associated smooth muscle cell proliferation (GO:1904707), positive regulation of vascular associated smooth muscle cell apoptotic process (GO:1905461), autophagy (GO:0006914), mitochondrion organization (GO:0007005)

GO Molecular Function (6): GTPase activity (GO:0003924), GTP binding (GO:0005525), ubiquitin protein ligase binding (GO:0031625), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020)

Reactome top-level categories

8 top-level categories:

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

47 GO namespaces:

Category	Terms
mitochondrion organization	2
cytoplasm	2
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to topologically incorrect protein	1
mitochondrion	1
membrane organization	1
organelle fusion	1
cellular respiration	1
autophagosome assembly	1
intracellular protein localization	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
negative regulation of cell population proliferation	1
smooth muscle cell proliferation	1
regulation of smooth muscle cell proliferation	1
organelle localization	1
mitophagy	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
positive regulation of smooth muscle cell proliferation	1
regulation of vascular associated smooth muscle cell proliferation	1
vascular associated smooth muscle cell proliferation	1
positive regulation of smooth muscle cell apoptotic process	1
vascular associated smooth muscle cell apoptotic process	1
regulation of vascular associated smooth muscle cell apoptotic process	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
organelle organization	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
ubiquitin-like protein ligase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
cytoskeleton	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
aerobic respiration	BP	mutant phenotype
mitochondrial fusion	BP	mutant phenotype
mitochondrial membrane organization	BP	direct assay
mitochondrion localization	BP	direct assay
negative regulation of Ras protein signal transduction	BP	direct assay
positive regulation of vascular associated smooth muscle cell apoptotic process	BP	mutant phenotype
positive regulation of vascular associated smooth muscle cell proliferation	BP	mutant phenotype
protein localization to phagophore assembly site	BP	direct assay
mitochondrion	CC	direct assay
ubiquitin protein ligase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,859 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFN2	DNM1L	O00429	970
MFN2	FIS1	Q9Y3D6	951
MFN2	PINK1	Q9BXM7	932
MFN2	VDAC1	P21796	903
MFN2	MARCHF5	Q9NX47	895
MFN2	MFF	Q9GZY8	893
MFN2	GDAP1	Q8TB36	887
MFN2	PRKN	O60260	880
MFN2	CYCS	P00001	854
MFN2	OPA1	O60313	841
MFN2	KIF1B	O60333	808
MFN2	TOMM20	Q15388	807
MFN2	TFAM	Q00059	804
MFN2	DENR	O43583	791
MFN2	MIEF2	Q96C03	784

IntAct

Human interaction partners of MFN2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
MFN1	physical association	0.790	5
MARCHF5	association	0.670	4
PRKN	physical association	0.580	3
BAK1	association	0.530	2
GHITM	association	0.530	1
LRRK2	physical association	0.460	3
SAMM50	physical association	0.400	2
FADD	physical association	0.400	1
TCHP	physical association	0.400	1
VCP	physical association	0.400	1
AKAP1	association	0.350	3
CYP2C19	association	0.350	1

BioGRID (204 interactions; top human partners by supporting records): MARCH5 (Affinity Capture-MS; 11 records), PARK2 (Affinity Capture-Western; 10 records), MFN1 (Affinity Capture-MS; 5 records), SLC25A46 (Affinity Capture-Western; 4 records), AKAP1 (Proximity Label-MS; 3 records), APOA1BP (Affinity Capture-Western; 2 records), C3orf58 (Affinity Capture-Western; 2 records), C9orf72 (Proximity Label-MS; 2 records), GHITM (Affinity Capture-MS; 2 records), HUWE1 (Affinity Capture-Western; 2 records), MAVS (Proximity Label-MS; 2 records), MTCH1 (Proximity Label-MS; 2 records), OCIAD1 (Proximity Label-MS; 2 records), REEP5 (Affinity Capture-MS; 2 records), SLC25A38 (Affinity Capture-Western; 2 records)

SIGNOR signaling

11 signaling interactions:

A	Effect	B	Mechanism
MAPK9	down-regulates	MFN2	phosphorylation
STOML2	“up-regulates quantity by expression”	MFN2	“transcriptional regulation”
PRKN	“down-regulates quantity”	MFN2	ubiquitination
HUWE1	“down-regulates quantity by destabilization”	MFN2	ubiquitination
MFN2	up-regulates	Mitochondrial_fusion
PINK1	“down-regulates quantity”	MFN2	ubiquitination
MAPK8	“down-regulates quantity”	MFN2	phosphorylation
PINK1	“down-regulates quantity”	MFN2	phosphorylation
MARCHF5	“up-regulates activity”	MFN2	ubiquitination
PKA	“up-regulates activity”	MFN2	phosphorylation
AMFR	“down-regulates quantity by destabilization”	MFN2	polyubiquitination

Disease & clinical

Genetic variants

Variant evidence for MFN2: 1,448 ClinVar records (183 pathogenic / likely pathogenic); 6 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,448 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	97
Likely pathogenic	86
Uncertain significance	670
Likely benign	352
Benign	62

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 183 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2276	NM_014874.4(MFN2):c.280C>T (p.Arg94Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	24
2281	NM_014874.4(MFN2):c.310C>T (p.Arg104Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	23
2268	NM_014874.4(MFN2):c.281G>A (p.Arg94Gln)	Pathogenic	criteria provided, multiple submitters, no conflicts	19
2278	NM_014874.4(MFN2):c.1090C>T (p.Arg364Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	18
2270	NM_014874.4(MFN2):c.227T>C (p.Leu76Pro)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
217164	NM_014874.4(MFN2):c.494A>G (p.His165Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
2279	NM_014874.4(MFN2):c.617C>T (p.Thr206Ile)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
245768	NM_014874.4(MFN2):c.1198C>T (p.Arg400Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
243066	NM_014874.4(MFN2):c.730G>A (p.Val244Met)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
217162	NM_014874.4(MFN2):c.2256C>A (p.Tyr752Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
439897	NM_014874.4(MFN2):c.493C>T (p.His165Tyr)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
476769	NM_014874.4(MFN2):c.2222T>G (p.Leu741Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
572157	NM_014874.4(MFN2):c.1091G>C (p.Arg364Pro)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
572169	NM_014874.4(MFN2):c.2251C>T (p.Gln751Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
637718	NM_014874.4(MFN2):c.475-1G>C	Pathogenic	criteria provided, multiple submitters, no conflicts	3

Per-variant reference — Sugi Variant

Explore MFN2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 1,495):

Position(s)	Effect	Δscore	Sites
1:11989344–11989345	donor_loss	1.0000	5
1:11992548	acceptor_gain	1.0000
1:11992691–11992692	donor_loss	1.0000	5
1:11996154–11996155	acceptor_loss	1.0000	3
1:11996319–11996320	donor_loss	1.0000	5
1:11997288	acceptor_gain	1.0000
1:11997295–11997296	acceptor_loss	1.0000	2
1:11997422–11997423	donor_loss	1.0000	5
1:12001392	acceptor_gain	1.0000
1:12001399–12001400	acceptor_loss	1.0000	3

AlphaMissense

2,158 missense substitutions predicted likely pathogenic (of 5,036 scored), across 542 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M97	9	0.945	0.997
M234	9	0.923	0.997
D199	8	0.998	0.999
D221	8	0.998	0.999
D261	8	0.998	1.000
H277	8	0.996	0.999
F223	8	0.992	0.999
F32	8	0.990	0.999
F358	8	0.990	1.000
S106	8	0.989	0.999
F341	8	0.989	0.999
F133	8	0.987	0.999
F254	8	0.987	1.000
F545	8	0.987	0.999
F241	8	0.986	0.998
N258	8	0.986	1.000
H361	8	0.984	0.997
F748	8	0.984	0.999
H128	8	0.980	0.992
F284	8	0.980	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.58e-08
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000281
Colon Adenocarcinoma (TCGA)	favorable	0.0008

Disease associations

OMIM: gene MIM:608507 | disease phenotypes: MIM:609260, MIM:118220, MIM:617087, MIM:601152, MIM:151800, MIM:606482, MIM:609129

GenCC curated gene-disease

8 curated gene-disease records:

Disease	Classification	Inheritance	Records
Charcot-Marie-Tooth disease type 2A2	Definitive	Semidominant	3
Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;	Definitive	Autosomal recessive	2
neuropathy, hereditary motor and sensory, type 6A	Definitive	Autosomal dominant
hereditary motor and sensory neuropathy	Strong	Semidominant
multiple symmetric lipomatosis with partial lipodystrophy	Strong	Autosomal recessive
multiple symmetric lipomatosis	Supportive	Autosomal dominant
severe early-onset axonal neuropathy due to MFN2 deficiency	Supportive	Autosomal recessive
hereditary motor and sensory neuropathy type 6	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
multiple symmetric lipomatosis with partial lipodystrophy	Definitive	AR
Charcot-Marie-Tooth disease type 2A2	Definitive	SD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (16 panels, 16 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

16 panels:

Panel	Rating
Adult-onset neurological disorders	green
DDG2P	green
Hereditary ataxia, adult onset	green
Hereditary neuropathy	green
Hereditary neuropathy or pain disorder	green
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Mitochondrial DNA maintenance disorder	green
Mitochondrial disorders	green
Optic neuropathy	green
Paediatric disorders	green
Possible mitochondrial disorder, nuclear genes	green
Severe insulin resistance and lipodystrophy syndromes	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (21): Charcot-Marie-Tooth disease type 2 (MONDO:0018993), cerebral palsy (MONDO:0006497), Charcot-Marie-Tooth disease type 2A2 (MONDO:0012231), Charcot-Marie-Tooth disease (MONDO:0015626), severe early-onset axonal neuropathy due to MFN2 deficiency (MONDO:0019549), Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; (MONDO:0014906), cerebellar ataxia (MONDO:0000437), neuropathy, hereditary motor and sensory, type 6A (MONDO:0011002), hereditary motor and sensory neuropathy type 6 (MONDO:0019551), microcephaly (MONDO:0001149), hyperpigmentation of the skin (MONDO:0019289), Charcot-Marie-Tooth disease type 4 (MONDO:0018995), axonal neuropathy (MONDO:0004183), multiple symmetric lipomatosis (MONDO:0007908), Charcot-Marie-Tooth disease dominant intermediate B (MONDO:0011674), multiple system atrophy, cerebellar type (MONDO:0016418), auditory neuropathy (MONDO:0021944), hereditary motor neuron disease (MONDO:0024257), peripheral neuropathy (MONDO:0005244), hereditary motor and sensory neuropathy (MONDO:0015358), multiple symmetric lipomatosis with partial lipodystrophy (MONDO:1060153)

Orphanet (13): Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746), Autosomal dominant Charcot-Marie-Tooth disease type 2A2 (Orphanet:99947), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Severe early-onset axonal neuropathy due to MFN2 deficiency (Orphanet:90118), Rare ataxia (Orphanet:102002), Hereditary motor and sensory neuropathy type 6 (Orphanet:90120), Hyperpigmentation of the skin (Orphanet:79375), Charcot-Marie-Tooth disease type 4 (Orphanet:64749), Multiple symmetric lipomatosis (Orphanet:2398), Autosomal dominant intermediate Charcot-Marie-Tooth disease type B (Orphanet:100044), Autosomal dominant Charcot-Marie-Tooth disease type 2M (Orphanet:228179), Multiple system atrophy, cerebellar type (Orphanet:227510), Genetic motor neuron disease (Orphanet:98505)

HPO phenotypes

showing 60 of 111 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000238	Hydrocephalus
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000458	Anosmia
HP:0000543	Optic disc pallor
HP:0000551	Color vision defect
HP:0000603	Central scotoma
HP:0000641	Dysmetric saccades
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000662	Nyctalopia
HP:0000855	Insulin resistance
HP:0001012	Multiple lipomas
HP:0001155	Abnormality of the hand
HP:0001257	Spasticity
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001276	Hypertonia
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001315	Diminished deep tendon reflex
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001371	Flexion contracture
HP:0001387	Joint stiffness
HP:0001604	Vocal cord paresis
HP:0001605	Vocal cord paralysis
HP:0001609	Hoarse voice
HP:0001618	Dysphonia
HP:0001620	Abnormally high-pitched voice
HP:0001760	Abnormal foot morphology
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001765	Hammertoe
HP:0002143	Abnormal spinal cord morphology
HP:0002174	Postural tremor
HP:0002194	Delayed gross motor development
HP:0002240	Hepatomegaly
HP:0002359	Frequent falls
HP:0002378	Hand tremor
HP:0002403	Positive Romberg sign
HP:0002460	Distal muscle weakness
HP:0002495	Impaired vibratory sensation
HP:0002522	Areflexia of lower limbs
HP:0002601	Paresis of extensor muscles of the big toe
HP:0002650	Scoliosis
HP:0002747	Respiratory insufficiency due to muscle weakness
HP:0002808	Kyphosis
HP:0002829	Arthralgia
HP:0002936	Distal sensory impairment
HP:0002938	Lumbar hyperlordosis
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase activity
HP:0003323	Progressive muscle weakness
HP:0003376	Steppage gait
HP:0003378	Axonal degeneration/regeneration

GWAS associations

6 associations:

Study	Trait	p-value
GCST90002400_397	Plateletcrit	5e-101
GCST90002402_698	Platelet count	2e-67
GCST004923_1	Tuberculosis	1e-11
GCST007578_3	Plasma homocysteine levels	7e-9
GCST001337_1	Platelet count	1e-8
GCST002740_36	Inflammatory skin disease	1e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004578	homocysteine measurement
EFO:0007985	platelet crit

MeSH disease descriptors

7 disease descriptors:

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D002547	Cerebral Palsy	C10.228.140.140.254
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D015417	Hereditary Sensory and Motor Neuropathy	C10.500.300; C10.574.500.495; C10.668.829.800.300; C16.131.666.300; C16.320.400.375
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C538268	Auditory neuropathy *(supp.)*
C563757	Charcot-Marie-Tooth Disease, Axonal, Type 2A2 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630807 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Mitofusin proteins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 13B [PMID: 32506913]	Activation	8.11	pEC50

Binding affinities (BindingDB)

2 measured of 3 human assays (3 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4639460	EC50	2.5 nM
CHEMBL5088708	EC50	3.8 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.60	EC50	2.49	nM	CHEMBL4639460
8.42	EC50	3.8	nM	CHEMBL5088708

PubChem BioAssay actives

2 with measured affinity, of 7 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[3-(5-cyclopropyl-4-phenyl-1,2,4-triazol-3-yl)propyl]-3-(2-methylcyclohexyl)urea	1812970: Activation of human Mitofusin-2 expressed in MEF cells assessed as enhancement of mitochondrial elongation and polarization measured after 48 hrs by Hoechst staining based confocal microscopy analysis	ec50	0.0025	uM
cis-(1R,2R)-N-(4-hydroxycyclohexyl)-2-(3-phenylpropyl)cyclopropane-1-carboxamide	1812970: Activation of human Mitofusin-2 expressed in MEF cells assessed as enhancement of mitochondrial elongation and polarization measured after 48 hrs by Hoechst staining based confocal microscopy analysis	ec50	0.0038	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Rotenone	decreases reaction, increases expression, affects localization, decreases expression	4
sodium arsenite	affects reaction, decreases expression, increases expression, affects binding, increases reaction	3
Acetylcysteine	increases glutathionylation, affects cotreatment, increases degradation, decreases expression, decreases reaction (+1 more)	3
Cadmium Chloride	decreases localization, increases expression, increases degradation, affects binding, increases reaction (+4 more)	3
alpha-Chlorohydrin	decreases expression, decreases reaction	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Cadmium	decreases reaction, decreases expression, decreases localization, increases expression, increases degradation (+4 more)	2
Carbonyl Cyanide m-Chlorophenyl Hydrazone	affects cotreatment, decreases reaction, increases degradation, affects localization, decreases expression (+1 more)	2
Doxorubicin	decreases expression	2
Fluorouracil	affects expression, increases expression	2
Particulate Matter	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
NMS-873	decreases reaction, increases abundance, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
nobiletin	increases expression, decreases reaction	1
sodium arsenate	decreases reaction, increases expression	1
o,p’-DDT	increases expression	1
mono-(2-ethylhexyl)phthalate	affects cotreatment, decreases reaction, increases degradation, increases reaction	1
fisetin	decreases expression, decreases reaction	1
cobaltous chloride	affects expression	1
salvin	decreases expression, decreases reaction	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	decreases methylation	1
acipimox	increases expression	1
polydatin	decreases reaction, increases expression	1
calpeptin	decreases reaction, increases degradation	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases abundance, decreases expression, decreases reaction	1
amyloid beta-protein (1-42)	decreases expression, decreases reaction	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4618565	Binding	Activation of human MFN2 expressed in Mfn1 and Mfn2 double-null mouse MEF assessed as induction of open/active conformation at 5 uM incubated for 1 to 4 hrs by FRET assay	Discovery of 6-Phenylhexanamide Derivatives as Potent Stereoselective Mitofusin Activators for the Treatment of Mitochondrial Diseases. — *J Med Chem*

Cellosaurus cell lines

24 cell lines: 14 induced pluripotent stem cell, 5 embryonic stem cell, 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A9XI	JUCTCi012-A	Induced pluripotent stem cell	Female
CVCL_A9XJ	JUCTCi012-B	Induced pluripotent stem cell	Female
CVCL_A9XK	JUCTCi012-C	Induced pluripotent stem cell	Female
CVCL_B1B7	Abcam HEK293 MFN2 KO	Transformed cell line	Female
CVCL_B7E9	NYSCF-AG0002-01-MR	Induced pluripotent stem cell	Male
CVCL_C0J2	JUCTCi019-A	Induced pluripotent stem cell	Male
CVCL_C0J3	JUCTCi019-B	Induced pluripotent stem cell	Male
CVCL_C0J4	JUCTCi019-C	Induced pluripotent stem cell	Male
CVCL_E2C4	HAP1 MFN2 (-) 2	Cancer cell line	Male
CVCL_E2C5	HAP1 MFN2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 305 trials:

NCT	Phase	Status	Title
NCT00154830	Phase 4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	Phase 4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	Phase 4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	Phase 4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	Phase 4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	Phase 4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	Phase 4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	Phase 4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	Phase 4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	Phase 4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	Phase 4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	Phase 4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	Phase 4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	Phase 4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	Phase 4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
NCT06189781	Phase 4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
NCT00014989	Phase 3	COMPLETED	Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
NCT00065949	Phase 3	UNKNOWN	Magnesium Sulfate to Prevent Brain Injury in Premature Infants
NCT00367068	Phase 3	COMPLETED	Dutch National ITB Study in Children With Cerebral Palsy
NCT00491894	Phase 3	COMPLETED	Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions
NCT00632528	Phase 3	COMPLETED	MEOPA to Improve Physical Therapy Results After Multilevel Surgery
NCT00822029	Phase 3	TERMINATED	Use of Oral Bisphosphonates in the Treatment of Osteoporosis of Non-walking Children With Cerebral Palsy
NCT00922077	Phase 3	COMPLETED	Individualized Neurodevelopmental Treatment
NCT01249417	Phase 3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Study
NCT01251380	Phase 3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Follow-on Study
NCT01437644	Phase 3	COMPLETED	The Post-Operative Pain in Cerebral Palsy (POPPIES) Trial
NCT01492608	Phase 3	COMPLETED	Magnesium Sulphate for Preterm Birth (MASP Study)
NCT01603602	Phase 3	COMPLETED	BOTOX® Treatment in Pediatric Upper Limb Spasticity
NCT01603615	Phase 3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Upper Limb Spasticity
NCT01603628	Phase 3	COMPLETED	BOTOX® Treatment in Pediatric Lower Limb Spasticity
NCT01603641	Phase 3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Lower Limb Spasticity
NCT01633736	Phase 3	UNKNOWN	Targeted Hip Strength Training in Children With Cerebral Palsy (CP)
NCT01898520	Phase 3	COMPLETED	A Safety, Efficacy and Tolerability Study of Sativex for the Treatment of Spasticity in Children Aged 8 to 18 Years
NCT01929434	Phase 3	COMPLETED	Efficacy of Stem Cell Transplantation Compared to Rehabilitation Treatment of Patients With Cerebral Paralysis
NCT02002884	Phase 3	COMPLETED	Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Arm(s) or of Arm(s) and Leg(s) in Cerebral Palsy
NCT02270736	Phase 3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02839785	Phase 3	TERMINATED	Analgesia and Physiotherapy in Children With Cerebral Palsy (ANTALKINECP)
NCT03110341	Phase 3	UNKNOWN	Effect of Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome
NCT03302871	Phase 3	COMPLETED	Integrated Management Enhances Functional Gains in Children With Cerebral Palsy Treated by BoNT-A
NCT03306212	Phase 3	COMPLETED	Efficacy of Intermittent Serial Casting on Spastic Wrist Flexion Deformity
NCT03469999	Phase 3	COMPLETED	Effect of Dysport Injections on Energy Expenditure and Walking Efficiency in Children With Cerebral Palsy
NCT03472261	Phase 3	COMPLETED	Integrated Management of Pronation Deformity in Cerebral Palsy
NCT03616067	Phase 3	TERMINATED	Evaluation of the Efficacy of the Injection of Botulinum Toxin A vs Scopolamine Patches in the Treatment of Drooling in Children With Cerebral Palsy
NCT05206513	Phase 3	COMPLETED	Study to Assess the Efficacy, Safety, and Tolerability of Valbenazine for the Treatment of Dyskinesia Due to Cerebral Palsy
NCT06128616	Phase 3	UNKNOWN	Efficacy of Extracorporeal Shock Wave Therapy in Children With Cerebral Palsy
NCT06840158	Phase 3	COMPLETED	Double-blind Comparative Randomized Multicenter
NCT07524972	Phase 3	RECRUITING	Antenatal Magnesium Sulphate in High-Risk Preterm Patients
NCT07672158	Phase 3	NOT_YET_RECRUITING	Tranexamic Acid to Reduce Blood Loss After Varus Derotation Osteotomy
NCT00271635	Phase 2	COMPLETED	Ascorbic Acid Treatment in CMT1A Trial (AATIC)
NCT00060957	Phase 2	COMPLETED	Botulinum Toxin (BOTOX) for Cerebral Palsy
NCT00061139	Phase 2	UNKNOWN	Constraint-Based Therapy to Improve Motor Function in Children With Cerebral Palsy
NCT00114075	Phase 2	COMPLETED	Effects of Walking Analysis on Surgical Outcomes
NCT00221247	Phase 2	COMPLETED	Acupuncture as Complementary Therapy for Cerebral Palsy
NCT00221611	Phase 2	COMPLETED	Intrathecal Administration of Baclofen (ITB) to Cerebral Palsy Patients With Therapy-Resistant Spasticity
NCT00295295	Phase 2	COMPLETED	Vibration Intervention to Improve Bone and Muscle in Children With Cerebral Palsy
NCT00413946	Phase 2	COMPLETED	Does Erythropoietin Improve Outcome in Very Preterm Infants?
NCT00455637	Phase 2	TERMINATED	Which is the Best Dose of Dysport in Helping With Hip Pain for Children With Cerebral Palsy?
NCT00467207	Phase 2	COMPLETED	Intensive Strength Training in Children With Cerebral Palsy - Effect on Hand Function
NCT01028833	Phase 2	COMPLETED	Effects of Power Mobility on Young Children With Severe Motor Impairments
NCT01115998	Phase 2	COMPLETED	Effect of Power Wheelchairs on the Development and Function of Young Children With Severe Physical Disabilities

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MFN2 across ~30M SureChEMBL compounds — explore on Sugi Predict.