NDUFS2

Summary

NDUFS2 (NADH:ubiquinone oxidoreductase core subunit S2, HGNC:7708) is a protein-coding gene on chromosome 1q23.3, encoding NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial (O75306). Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. It is a selective cancer dependency (DepMap: 40.6% of cell lines).

The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Mammalian mitochondrial complex I is composed of at least 43 different subunits, 7 of which are encoded by the mitochondrial genome, and the rest are the products of nuclear genes. The iron-sulfur protein fraction of complex I is made up of 7 subunits, including this gene product. Complex I catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4720 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 254 total — 6 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 78
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 40.6% of screened cell lines
• MANE Select transcript: NM_001377299

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7708
Approved symbol	NDUFS2
Name	NADH:ubiquinone oxidoreductase core subunit S2
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	CI-49
Ensembl gene	ENSG00000158864
Ensembl biotype	protein_coding
OMIM	602985
Entrez	4720

Gene structure

Transcript identifiers

Ensembl transcripts: 93 — 40 retained_intron, 23 nonsense_mediated_decay, 18 protein_coding, 12 protein_coding_CDS_not_defined

ENST00000367993, ENST00000392179, ENST00000465923, ENST00000467295, ENST00000468828, ENST00000473321, ENST00000475570, ENST00000478866, ENST00000479948, ENST00000480762, ENST00000483804, ENST00000492153, ENST00000493849, ENST00000496133, ENST00000496553, ENST00000676535, ENST00000676583, ENST00000676600, ENST00000676653, ENST00000676726, ENST00000676770, ENST00000676795, ENST00000676871, ENST00000676972, ENST00000676991, ENST00000677033, ENST00000677045, ENST00000677050, ENST00000677063, ENST00000677081, ENST00000677089, ENST00000677103, ENST00000677138, ENST00000677178, ENST00000677231, ENST00000677336, ENST00000677350, ENST00000677358, ENST00000677383, ENST00000677453, ENST00000677457, ENST00000677471, ENST00000677495, ENST00000677547, ENST00000677550, ENST00000677577, ENST00000677579, ENST00000677613, ENST00000677643, ENST00000677653, ENST00000677657, ENST00000677736, ENST00000677745, ENST00000677807, ENST00000677809, ENST00000677837, ENST00000677846, ENST00000677916, ENST00000677925, ENST00000677948, ENST00000678052, ENST00000678068, ENST00000678130, ENST00000678328, ENST00000678356, ENST00000678484, ENST00000678492, ENST00000678507, ENST00000678511, ENST00000678532, ENST00000678559, ENST00000678605, ENST00000678613, ENST00000678648, ENST00000678783, ENST00000678793, ENST00000678850, ENST00000678880, ENST00000678911, ENST00000678966, ENST00000678982, ENST00000679064, ENST00000679071, ENST00000679142, ENST00000679169, ENST00000679176, ENST00000679215, ENST00000679218, ENST00000679239, ENST00000679282, ENST00000873085, ENST00000960014, ENST00000960015

RefSeq mRNA: 8 — MANE Select: NM_001377299 NM_001166159, NM_001377298, NM_001377299, NM_001377300, NM_001377301, NM_001377302, NM_001410889, NM_004550

CCDS: CCDS1224, CCDS53404, CCDS91086

Canonical transcript exons

ENST00000676972 — 14 exons

Exon	Start	End
ENSE00001884216	161214156	161214395
ENSE00003464463	161203437	161203543
ENSE00003465746	161213649	161213732
ENSE00003466143	161210111	161210188
ENSE00003471424	161213864	161213921
ENSE00003489152	161206407	161206597
ENSE00003495523	161209857	161209931
ENSE00003541082	161213380	161213475
ENSE00003550227	161209193	161209313
ENSE00003567087	161212351	161212480
ENSE00003587080	161210591	161210710
ENSE00003634980	161210304	161210389
ENSE00003672735	161209483	161209595
ENSE00003906071	161202367	161202480

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 75.9535 / max 561.1559, expressed in 1824 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6217	75.4756	1824
6216	0.4779	298

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.19	gold quality
gastrocnemius	UBERON:0001388	99.01	gold quality
heart left ventricle	UBERON:0002084	98.98	gold quality
cardiac ventricle	UBERON:0002082	98.96	gold quality
mucosa of transverse colon	UBERON:0004991	98.84	gold quality
muscle of leg	UBERON:0001383	98.81	gold quality
right adrenal gland	UBERON:0001233	98.75	gold quality
heart right ventricle	UBERON:0002080	98.70	gold quality
right adrenal gland cortex	UBERON:0035827	98.70	gold quality
right atrium auricular region	UBERON:0006631	98.69	gold quality
left ventricle myocardium	UBERON:0006566	98.66	gold quality
muscle organ	UBERON:0001630	98.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.60	gold quality
cardiac atrium	UBERON:0002081	98.59	gold quality
left adrenal gland	UBERON:0001234	98.51	gold quality
heart	UBERON:0000948	98.47	gold quality
body of tongue	UBERON:0011876	98.37	gold quality
left adrenal gland cortex	UBERON:0035825	98.36	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.30	gold quality
diaphragm	UBERON:0001103	98.24	gold quality
skeletal muscle tissue	UBERON:0001134	98.21	gold quality
adrenal cortex	UBERON:0001235	98.20	gold quality
vastus lateralis	UBERON:0001379	98.20	gold quality
deltoid	UBERON:0001476	98.17	gold quality
left ovary	UBERON:0002119	98.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.15	gold quality
transverse colon	UBERON:0001157	98.14	gold quality
quadriceps femoris	UBERON:0001377	98.12	gold quality
adrenal gland	UBERON:0002369	98.10	gold quality
right ovary	UBERON:0002118	98.09	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	808.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting NDUFS2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-2277-3P	91.94	62.27	299

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 40.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Trx, dCBP, and Sbf1 are closely linked, physically and functionally, in the maintenance of Hox gene expression. (PMID:11701926)
• The Drosophila trithorax protein is a coactivator required to prevent re-establishment of polycomb silencing. (PMID:11973279)
• Genomic imprinting in Drosophila is maintained by the products of Suppressor of variegation and trithorax group, but not Polycomb group, genes. (PMID:12242505)
• Trithorax interacts with type 1 serine/threonine protein phosphatase. (PMID:12524522)
• This suggests that TRITHORAX bound to certain regulatory chromosome regions interacts with the adjacent elements of the nuclear scaffold, i.e., links the regions of actively transcribed genes with the nuclear matrix. (PMID:12669422)
• identified several members of the Polycomb and trithorax classes of genes required for the normal pattern of photoreceptor differentiation (PMID:15020417)
• Results suggest that protein phosphatase 1beta9C and Trithorax cooperate in Drosophila wing development. (PMID:15366010)
• Deletion analysis showed that the C-terminus of dDYRK2 modulated the interaction with SNR1 and TRX. (PMID:16671894)
• it is proposed that that the Trithorax complex, TAC1, promotes the mosaic pattern of Ubx expression by facilitating transcriptional elongation of bxd noncoding RNAs, which represses Ubx transcription (PMID:17174895)
• Data demonstrate that the Drosophila homologs of mixed-lineage leukemia protein and host cell factor 1, called Trithorax and dHCF, are both cleaved by Drosophila taspase 1. (PMID:17698583)
• Computational analysis ofmicroarray data, identified 25 clusters of genes potentially regulated by TRX; most of these clusters consist of genes that encode structural proteins involved in cuticle formation. (PMID:18783608)
• results indicate that DNA binding proteins serve as platforms to assist PcG and trxG binding. Furthermore, several DNA sequence features discriminate between PcG- and TRX-N-bound regions (PMID:19143474)
• Hsp90 cooperates with Trx at chromatin for maintaining the active expression state of targets like the Hox genes. (PMID:19144915)
• These findings establish a role for PRC2 and TRX in the modulation of organismal longevity and stress resistance and indicate that moderate perturbation of Polycomb silencing can increase longevity. (PMID:20018689)
• Polycomb and trithorax control genome expression by determining the alternative epigenetic states of chromatin for key developmental regulators (PMID:21254568)
• dHCF possesses Enhancer of TrxG and PcG (ETP) properties. (PMID:22174740)
• Data imply that Trx, Pc, and E(z) remain bound or rapidly rebind to nascent DNA in the absence of trimethylated histones during DNA replication in Drosophila embryos. (PMID:22921915)
• mutations in PcG components and in TrxG members found in chromatin remodeling complexes enhance the gcm dominant phenotype, suggesting a balanced action of these chromatin modifiers regulate Gcm function (PMID:23300465)
• CpG island encompassing the promoter and first exon of human DNMT3L gene is a PcG/TrX response element (PMID:24743422)
• From the Drosophila melanogaster vestigial (vg) Polycomb response element/Trithorax response element switches the status of the element. (PMID:25108384)
• Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor buttonhead. (PMID:25285447)
• Trithorax has a role in regulating systemic signaling during Drosophila imaginal disc regeneration (PMID:26487779)
• If ASH1 or TRX function is lost or reduced, heterochromatin can spread into these domains creating a sink that diverts heterochromatic proteins from other variegating locations, which then may express a suppressed phenotype. (PMID:27373142)
• Trithorax positively regulates gene expression in Drosophila and co-occupies PREs to antagonize Polycomb-dependent silencing. Trx-dependent H3K4 dimethylation (H3K4me2) marks Drosophila PREs and maintains the developmental expression pattern of nearby genes. (PMID:27447986)
• Taken together, these data indicate that Atrophin is a major Trithorax-like cofactor that functions to moderate developmental gene transcription. (PMID:28327288)
• Mrg15 is a subunit of the Ash1 complex, a stimulator of Ash1 enzymatic activity and a critical regulator of the TrxG protein function of Ash1 in Drosophila. (PMID:29158494)
• Control of the gene activity by polycomb and trithorax group proteins in Drosophila (PMID:29372960)
• we demonstrate that the evolutionary conserved Lim3 core promoter provides basic Lim3 expression, whereas structural changes in the Lim3 PRE of distal promoter provide stage-, and tissue-specific Lim3 expression. Therefore, we hypothesize that PcG/TrxG proteins, which are directly involved in Lim3 transcription regulation, participate in lifespan control. (PMID:29555581)
• Trx and Grx have both, common and specific protein Cys redox targets and that down regulation of either redoxin has markedly different metabolic outcomes. They reflect the delicate sensitivity of redox equilibrium to changes in any of the elements involved and the difficulty of forecasting metabolic responses to redox environmental changes. (PMID:30639960)
• Trx, Ash1, and CBP proteins are required for the correct chromosome segregation and that Ash1 and CBP mediate for Cid/CENP-A recruitment at centromeres through post-translational histone modifications. (PMID:31203392)
• Dynamic Competition of Polycomb and Trithorax in Transcriptional Programming. (PMID:31928411)
• Distinct Roles for COMPASS Core Subunits Set1, Trx, and Trr in the Epigenetic Regulation of Drosophila Heart Development. (PMID:38139143)
• Our results confirm that NDUFS2 is a mutational hotspot in Caucasian children with isolated complex I deficiency and recommend the routine diagnostic investigation of this gene in patients with Leigh or Leigh-like phenotypes. (PMID:20819849)
• The NDUFS2 mutation affects complex I enzymatic function. (PMID:22036843)
• study describes clinical, radiological, biochemical and molecular data of 6 patients with Leigh syndrome with novel mutations in NDUFV1 and NDUFS2; 2 siblings were compound heterozygotes for an undescribed E104A mutation in NDUFS2 (PMID:23266820)
• NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I. (PMID:24089531)
• Results found nominal significant associations of 2 SNPs in the NDUFS1 gene and 4 SNPs in the NDUFS2 gene with early onset schizophrenia (EOS), but none of these associations survived the Bonferroni correction. (PMID:26053550)
• compound heterozygosity for severe and hypomorphic NDUFS2 mutations can cause non-syndromic hereditary optic neuropathy. (PMID:28031252)
• findings uncover a novel S100A4 function and highlight its importance in controlling NDUFS2 expression to regulate the plasticity of mitochondrial metabolism and thereby promote the invasive and metastatic capacity in lung cancer (PMID:30885944)
• Complex I protein NDUFS2 is vital for growth, ROS generation, membrane integrity, apoptosis, and mitochondrial energetics. (PMID:33744462)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufs2	ENSDARG00000007526
mus_musculus	Ndufs2	ENSMUSG00000013593
rattus_norvegicus	Ndufs2	ENSRNOG00000038372
drosophila_melanogaster	ND-49L	FBGN0039331
drosophila_melanogaster	ND-49	FBGN0039909
caenorhabditis_elegans		WBGENE00001520
caenorhabditis_elegans		WBGENE00006463

Protein

Protein identifiers

NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial — O75306 (reviewed: O75306)

Alternative names: Complex I-49kD, NADH-ubiquinone oxidoreductase 49 kDa subunit

All UniProt accessions (18): O75306, A0A7I2V2B9, A0A7I2V2P1, A0A7I2V3J6, A0A7I2V410, A0A7I2V4G5, A0A7I2V4W5, A0A7I2V4X8, A0A7I2V517, A0A7I2V596, A0A7I2V5D5, A0A7I2V5E2, A0A7I2V5G4, A0A7I2V5X7, A0A7I2V630, A0A7I2YQD8, A0A7I2YQG7, A0A7I2YQX7

UniProt curated annotations — full annotation on UniProt →

Function. Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity of complex I. Essential for the assembly of complex I. Redox-sensitive, critical component of the oxygen-sensing pathway in the pulmonary vasculature which plays a key role in acute pulmonary oxygen-sensing and hypoxic pulmonary vasoconstriction. Plays an important role in carotid body sensing of hypoxia. Essential for glia-like neural stem and progenitor cell proliferation, differentiation and subsequent oligodendrocyte or neuronal maturation.

Subunit / interactions. Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits. Component of the iron-sulfur (IP) fragment of the enzyme. Interacts with NDUFAF3. Interacts with NDUFAF7. Interacts with CERS2.

Subcellular location. Mitochondrion inner membrane.

Post-translational modifications. Dimethylation at Arg-118 by NDUFAF7 takes place after NDUFS2 assembles into the complex I, leading to stabilize the early intermediate complex.

Disease relevance. Mitochondrial complex I deficiency, nuclear type 6 (MC1DN6) [MIM:618228] A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN6 transmission pattern is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry. Leber-like hereditary optic neuropathy, autosomal recessive 2 (LHONAR2) [MIM:620569] An autosomal recessive form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. LHONAR2 is characterized by subacute bilateral or asymmetrical visual loss, optic nerve pseudoedema and peripapillary telangiectasia in the early phase of the disease, and eventual partial recovery in some patients. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 [4Fe-4S] cluster.

Similarity. Belongs to the complex I 49 kDa subunit family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75306-1	1	yes
O75306-2	2

RefSeq proteins (8): NP_001159631, NP_001364227, NP_001364228, NP_001364229, NP_001364230, NP_001364231, NP_001397818, NP_004541 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001135	NADH_Q_OxRdtase_suD	Domain
IPR014029	NADH_UbQ_OxRdtase_49kDa_CS	Conserved_site
IPR022885	NDH1_su_D/H	Family
IPR029014	NiFe-Hase_large	Homologous_superfamily

Pfam: PF00346

Catalyzed reactions (Rhea), 1 shown:

• a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 H(+)(out) (RHEA:29091)

UniProt features (53 total): helix 18, strand 11, sequence variant 10, turn 5, binding site 3, modified residue 2, transit peptide 1, chain 1, sequence conflict 1, splice variant 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
9I4I	ELECTRON MICROSCOPY	2.63
9TI4	ELECTRON MICROSCOPY	2.66
5XTB	ELECTRON MICROSCOPY	3.4
9CWT	ELECTRON MICROSCOPY	3.44
5XTC	ELECTRON MICROSCOPY	3.7
5XTD	ELECTRON MICROSCOPY	3.7
5XTH	ELECTRON MICROSCOPY	3.9
5XTI	ELECTRON MICROSCOPY	17.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75306-F1	89.62	0.81

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 (3): 326; 332; 347

Post-translational modifications (2): 62, 118

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-611105	Respiratory electron transport
R-HSA-6799198	Complex I biogenesis
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism

MSigDB gene sets: 431 (showing top): MODULE_93, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, MODY_HIPPOCAMPUS_POSTNATAL, MODULE_77, LFA1_Q6, MORF_HDAC1, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_NEUROGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION

GO Biological Process (10): mitochondrial electron transport, NADH to ubiquinone (GO:0006120), aerobic respiration (GO:0009060), neurogenesis (GO:0022008), mitochondrial respiratory chain complex I assembly (GO:0032981), gliogenesis (GO:0042063), mitochondrial ATP synthesis coupled electron transport (GO:0042775), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), neural precursor cell proliferation (GO:0061351), cellular response to oxygen levels (GO:0071453), proton transmembrane transport (GO:1902600)

GO Molecular Function (13): NADH dehydrogenase (ubiquinone) activity (GO:0008137), electron transfer activity (GO:0009055), oxidoreductase activity, acting on NAD(P)H (GO:0016651), oxygen sensor activity (GO:0019826), ubiquitin protein ligase binding (GO:0031625), metal ion binding (GO:0046872), quinone binding (GO:0048038), NAD binding (GO:0051287), 4 iron, 4 sulfur cluster binding (GO:0051539), NADH dehydrogenase activity (GO:0003954), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), respiratory chain complex I (GO:0045271), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Respiratory electron transport	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
cellular respiration	1
nervous system development	1
cell differentiation	1
NADH dehydrogenase complex assembly	1
mitochondrial respiratory chain complex assembly	1
neurogenesis	1
ATP synthesis coupled electron transport	1
oxidative phosphorylation	1
proton motive force-driven ATP synthesis	1
cell population proliferation	1
response to oxygen levels	1
cellular response to chemical stimulus	1
monoatomic cation transmembrane transport	1
NADH dehydrogenase activity	1
electron transfer activity	1
proton transmembrane transporter activity	1
oxidoreduction-driven active transmembrane transporter activity	1
oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	1
active monoatomic ion transmembrane transporter activity	1
molecular_function	1
oxidoreductase activity	1
oxygen binding	1
molecular sensor activity	1
ubiquitin-like protein ligase binding	1
cation binding	1
small molecule binding	1
adenyl nucleotide binding	1
iron-sulfur cluster binding	1
oxidoreductase activity, acting on NAD(P)H	1
binding	1
catalytic activity	1
metal cluster binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

3815 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDUFS2	NDUFS3	O75489	999
NDUFS2	NDUFS7	O75251	998
NDUFS2	NDUFS8	O00217	998
NDUFS2	NDUFS1	P28331	998
NDUFS2	NDUFV1	P49821	996
NDUFS2	NDUFV2	P19404	993
NDUFS2	NDUFA5	Q16718	971
NDUFS2	NDUFS6	O75380	964
NDUFS2	NDUFS4	O43181	956
NDUFS2	NDUFA9	Q16795	914
NDUFS2	NDUFA10	O95299	905
NDUFS2	NDUFAF4	Q9P032	879
NDUFS2	MT-ND1	P03886	870
NDUFS2	NDUFA11	Q86Y39	869
NDUFS2	NDUFS5	O43920	858

IntAct

185 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS2	psi-mi:“MI:0914”(association)	0.850
NDUFS2	NDUFS3	psi-mi:“MI:0914”(association)	0.850
NDUFS3	NDUFS2	psi-mi:“MI:0915”(physical association)	0.850
NDUFS2	NDUFS3	psi-mi:“MI:0915”(physical association)	0.850
NDUFA9	NDUFS2	psi-mi:“MI:0915”(physical association)	0.740
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
NDUFV2	NDUFS2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
NDUFS7	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFA13	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFA9	NDUFS4	psi-mi:“MI:0914”(association)	0.640

BioGRID (412): NDUFS2 (Affinity Capture-RNA), NDUFS2 (Affinity Capture-RNA), NDUFS2 (Affinity Capture-RNA), NDUFS2 (Affinity Capture-MS), NDUFS2 (Affinity Capture-MS), NDUFS2 (Affinity Capture-MS), NDUFS2 (Affinity Capture-MS), NDUFS2 (Affinity Capture-MS), DLD (Co-fractionation), LMAN2 (Co-fractionation), NDUFS1 (Co-fractionation), NDUFS2 (Co-fractionation), NDUFS2 (Co-fractionation), NDUFS2 (Co-fractionation), NDUFS2 (Co-fractionation)

ESM2 similar proteins: A0QJV0, A0QU33, A1BF35, A2CD94, A4FPT8, A4SF45, A5FX11, A5GP75, A5GWA1, A5VAM0, A5VPY6, A6X1N0, A9B4Z7, A9MAI2, B0CLD2, B0SZ49, B1ZRT0, B2S546, B3PW00, B4RCM6, B5ZYL5, B6JGW3, O75306, P17694, P22142, Q0I6T6, Q0MQG3, Q0MQG4, Q0MQG5, Q135X7, Q1GTK0, Q1MIL2, Q28T72, Q2G5Y6, Q2K9T1, Q2NA64, Q2YNG0, Q31ME6, Q3AGW8, Q3AVZ9

Diamond homologs: A0LDS4, A0LRI4, A0PR41, A0QJV0, A0QU33, A1K5B1, A1KNE4, A1SE30, A1T6A3, A1TLL9, A1UDA1, A1W4M5, A2SFM9, A3PWR8, A4FPT8, A4TDA8, A4XC35, A5CES2, A5FX11, A5G9B6, A5U7G4, A5UZH7, A6UFK4, A7NIV9, A8EZ86, A8F1C5, A8GN50, A8GRR5, A8GX80, A8LC98, A8M619, A9B4Z7, A9BNB1, A9CJA9, A9HRT9, A9WFB4, B0BX71, B0ULK7, B1MPG7, B1W516

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NDUFS2	“form complex”	“NADH-ubiquinone oxidoreductase-Mitochondrial respiratory chain complex I”	binding
CDK1	“up-regulates activity”	NDUFS2	phosphorylation
CyclinB/CDK1	“up-regulates activity”	NDUFS2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Complex I biogenesis	29	48.0×	2e-40
Respiratory electron transport	30	28.6×	3e-34
Aerobic respiration and respiratory electron transport	30	26.6×	2e-33
Mitochondrial protein degradation	10	11.4×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	21	61.7×	9e-31
proton motive force-driven mitochondrial ATP synthesis	23	49.6×	7e-31
mitochondrial respiratory chain complex I assembly	14	47.2×	3e-18
aerobic respiration	23	46.7×	1e-30

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	6
Uncertain significance	109
Likely benign	72
Benign	16

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1451468	NM_001377299.1(NDUFS2):c.128G>A (p.Trp43Ter)	Pathogenic
2627943	NM_001377299.1(NDUFS2):c.923A>G (p.Tyr308Cys)	Pathogenic
4312718	NM_001377299.1(NDUFS2):c.1102C>T (p.Arg368Ter)	Pathogenic
4714351	NM_001377299.1(NDUFS2):c.90del (p.Ser31fs)	Pathogenic
6710	NM_001377299.1(NDUFS2):c.686C>A (p.Pro229Gln)	Pathogenic
872511	NM_001377299.1(NDUFS2):c.442G>A (p.Glu148Lys)	Pathogenic
1324786	NM_001377299.1(NDUFS2):c.646C>T (p.Arg216Ter)	Likely pathogenic
1478205	NM_001377299.1(NDUFS2):c.1212+1G>T	Likely pathogenic
2010294	NM_001377299.1(NDUFS2):c.867-1G>A	Likely pathogenic
4312697	NM_001377299.1(NDUFS2):c.805C>T (p.Arg269Ter)	Likely pathogenic
522715	NM_001377299.1(NDUFS2):c.268G>A (p.Ala90Thr)	Likely pathogenic
6711	NM_001377299.1(NDUFS2):c.1237T>C (p.Ser413Pro)	Likely pathogenic

SpliceAI

1708 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161206399:C:G	acceptor_gain	1.0000
1:161206406:GAT:G	acceptor_gain	1.0000
1:161206406:GATGT:G	acceptor_gain	1.0000
1:161206525:G:GT	donor_gain	1.0000
1:161206560:GCAC:G	donor_gain	1.0000
1:161206567:G:GT	donor_gain	1.0000
1:161209188:CCCA:C	acceptor_loss	1.0000
1:161209189:CCA:C	acceptor_loss	1.0000
1:161209191:A:C	acceptor_loss	1.0000
1:161209192:G:GC	acceptor_loss	1.0000
1:161209472:T:TA	acceptor_gain	1.0000
1:161209479:ACAGT:A	acceptor_gain	1.0000
1:161209480:CA:C	acceptor_loss	1.0000
1:161209481:A:AG	acceptor_gain	1.0000
1:161209481:AGT:A	acceptor_gain	1.0000
1:161209482:G:A	acceptor_loss	1.0000
1:161209482:G:GG	acceptor_gain	1.0000
1:161209482:GT:G	acceptor_gain	1.0000
1:161209482:GTG:G	acceptor_gain	1.0000
1:161209482:GTGC:G	acceptor_gain	1.0000
1:161209482:GTGCT:G	acceptor_gain	1.0000
1:161209592:GAAG:G	donor_gain	1.0000
1:161209594:AGGTA:A	donor_loss	1.0000
1:161209596:GTAAG:G	donor_loss	1.0000
1:161209597:T:G	donor_loss	1.0000
1:161210302:A:AG	acceptor_gain	1.0000
1:161210303:G:GG	acceptor_gain	1.0000
1:161210383:GTTT:G	donor_gain	1.0000
1:161210384:TTTT:T	donor_gain	1.0000
1:161210586:CACA:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000215905 (1:161201143 C>T), RS1000247065 (1:161201522 A>T), RS1000550277 (1:161199368 G>A), RS1000852820 (1:161198252 T>C), RS1000861295 (1:161212740 G>T), RS1000905157 (1:161198500 G>A), RS1000920945 (1:161205384 T>G), RS1000963834 (1:161198002 C>T), RS1000987613 (1:161199714 A>G), RS1001046124 (1:161211509 G>A,C,T), RS1001182443 (1:161196947 C>T), RS1001236405 (1:161197189 C>T), RS1001246555 (1:161202840 A>G), RS1001357326 (1:161195874 A>G), RS1001373653 (1:161203271 C>G,T)

Disease associations

OMIM: gene MIM:602985 | disease phenotypes: MIM:618228, MIM:252010, MIM:620569, MIM:535000

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex I deficiency, nuclear type 6	Definitive	Autosomal recessive
Leber hereditary optic neuropathy	Supportive	Mitochondrial
Leigh syndrome with leukodystrophy	Supportive	Autosomal recessive
mitochondrial complex I deficiency	Supportive	Autosomal recessive
Leigh syndrome with cardiomyopathy	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR
Leigh syndrome	Definitive	AR

Mondo (8): mitochondrial complex I deficiency, nuclear type 6 (MONDO:0032611), mitochondrial complex I deficiency, nuclear type 1 (MONDO:0100224), optic atrophy (MONDO:0003608), mitochondrial complex I deficiency (MONDO:0100133), Leber-like hereditary optic neuropathy, autosomal recessive 2 (MONDO:0958197), Leber hereditary optic neuropathy (MONDO:0010788), (MONDO:0016815), Leigh syndrome with cardiomyopathy (MONDO:0019083)

Orphanet (2): Isolated complex I deficiency (Orphanet:2609), Leber hereditary optic neuropathy (Orphanet:104)

HPO phenotypes

78 total (30 of 78 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000114	Proximal tubulopathy
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000512	Abnormal electroretinogram
HP:0000529	Progressive visual loss
HP:0000543	Optic disc pallor
HP:0000551	Color vision defect
HP:0000576	Centrocecal scotoma
HP:0000603	Central scotoma
HP:0000618	Blindness
HP:0000622	Blurred vision
HP:0000639	Nystagmus
HP:0000642	Red-green dyschromatopsia
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000666	Horizontal nystagmus
HP:0000817	Reduced eye contact
HP:0000819	Diabetes mellitus
HP:0001138	Optic neuropathy
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004608_41	Granulocyte percentage of myeloid white cells	2.000000e-10
GCST005038_11	Allergic disease (asthma, hay fever or eczema)	1.000000e-11
GCST007797_50	Asthma onset (childhood vs adult)	1.000000e-06
GCST007798_9	Asthma	9.000000e-12
GCST007800_18	Asthma (childhood onset)	3.000000e-32
GCST008916_64	Asthma	2.000000e-08
GCST009719_20	Allergic rhinitis	4.000000e-10
GCST009720_86	Asthma	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0004847	age at onset

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D029242	Optic Atrophy, Hereditary, Leber	C10.292.700.225.500.400; C10.574.500.662.400; C11.270.564.400; C11.640.451.451.400; C16.320.290.564.400; C16.320.400.630.400; C18.452.660.670
C537475	Mitochondrial complex I deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363065 (PROTEIN COMPLEX), CHEMBL3039 (SINGLE PROTEIN)

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

ChEMBL bioactivities

16 potent at pChembl≥5 of 26 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.48	IC50	33	nM	CHEMBL4798829
7.34	Kd	45.26	nM	CHEMBL3752910
7.34	ED50	45.26	nM	CHEMBL3752910
7.10	IC50	79	nM	CHEMBL4798829
6.06	IC50	870	nM	R-(+)-MARMIN-6’-UNDECANOATE
6.04	IC50	920	nM	R-(+)-MARMIN-6’-LINOLEATE
5.91	Kd	1236	nM	CHEMBL5653589
5.91	ED50	1236	nM	CHEMBL5653589
5.63	IC50	2350	nM	R-(+)-MARMIN-6’-LINOLEATE
5.51	IC50	3080	nM	R-(+)-MARMIN-6’-OCTANOATE
5.43	IC50	3670	nM	R-(+)-MARMIN-6’-UNDECANOATE
5.43	IC50	3710	nM	R-(+)-MARMIN-6’-OCTANOATE
5.31	IC50	4900	nM	(+)-9’-ISOVALEROXYLARICIRESINOL
5.04	IC50	9100	nM	(+)-9’-ISOVALEROXYLARICIRESINOL

PubChem BioAssay actives

10 with measured affinity, of 32 total; 6 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148853: Binding affinity to human NDUFS2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0453	uM
[(E,3R)-2-hydroxy-2,6-dimethyl-8-(2-oxochromen-7-yl)oxyoct-6-en-3-yl] undecanoate	739270: Inhibition of mitochondrial ETC complex 1 in human T47D cells assessed as inhibition of 1% O2-induced HIF1 activation incubated for 30 mins prior to 1% O2-challenge measured after 16 hrs by luciferase reporter assay	ic50	0.8700	uM
[(E,3R)-2-hydroxy-2,6-dimethyl-8-(2-oxochromen-7-yl)oxyoct-6-en-3-yl] (9Z,12Z)-octadeca-9,12-dienoate	739270: Inhibition of mitochondrial ETC complex 1 in human T47D cells assessed as inhibition of 1% O2-induced HIF1 activation incubated for 30 mins prior to 1% O2-challenge measured after 16 hrs by luciferase reporter assay	ic50	0.9200	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148853: Binding affinity to human NDUFS2 incubated for 45 mins by Kinobead based pull down assay	kd	1.2362	uM
[(E,3R)-2-hydroxy-2,6-dimethyl-8-(2-oxochromen-7-yl)oxyoct-6-en-3-yl] octanoate	739270: Inhibition of mitochondrial ETC complex 1 in human T47D cells assessed as inhibition of 1% O2-induced HIF1 activation incubated for 30 mins prior to 1% O2-challenge measured after 16 hrs by luciferase reporter assay	ic50	3.0800	uM
[(2S,3R,4R)-2-(4-hydroxy-3-methoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-3-yl]methyl 3-methylbutanoate	739269: Inhibition of mitochondrial ETC complex 1 in human T47D cells assessed as inhibition of 1,10-phenanthroline-induced HIF1 activation incubated for 30 mins prior to 1,10-phenanthroline-challenge measured after 16 hrs by luciferase reporter assay	ic50	4.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects cotreatment, decreases expression	3
bisphenol A	increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Arsenic	increases methylation, affects cotreatment, decreases expression, increases abundance	2
Valproic Acid	increases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Aerosols	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cocaine	affects expression	1
Doxorubicin	increases expression	1
Isoniazid	decreases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 10 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2353025	Binding	Inhibition of mitochondrial ETC complex 1 in human T47D cells assessed as inhibition of 1% O2-induced HIF1 activation at 30 uM incubated for 30 mins prior to 1% O2-challenge measured after 16 hrs by luciferase reporter assay	Semisynthetic studies identify mitochondria poisons from botanical dietary supplements–geranyloxycoumarins from Aegle marmelos. — Bioorg Med Chem
CHEMBL5210044	Functional	Affinity Phenotypic Cellular interaction (Proliferation assay (CellTiter-Glo ATP assay in human lung H1299 cells)) EUB0000752a NDUFS2	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 2 transformed cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0D2	HEK293 NDUSF2 KO	Transformed cell line	Female
CVCL_D1P5	Abcam K-562 NDUFS2 KO	Cancer cell line	Female
CVCL_D2KQ	Abcam Raji NDUFS2 KO	Cancer cell line	Male
CVCL_D9L4	Ubigene HEK293 NDUFS2 KO	Transformed cell line	Female
CVCL_EQ48	8807	Finite cell line	Female
CVCL_TA18	HAP1 NDUFS2 (-) 1	Cancer cell line	Male
CVCL_TA19	HAP1 NDUFS2 (-) 2	Cancer cell line	Male
CVCL_WQ07	Abcam Jurkat NDUFS2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03293524	PHASE3	COMPLETED	Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year
NCT03406104	PHASE3	COMPLETED	RESCUE and REVERSE Long-term Follow-up
NCT07406854	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3, Multicenter, Randomized, Double-Masked, Sham-Controlled Clinical Trial for Leber’s Hereditary Optic Neuropathy (LHON) Associated With ND4 Mutation
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT02176733	PHASE2	UNKNOWN	Trial of Cyclosporine in the Acute Phase of Leber Hereditary Optic Neuropathy
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT03153293	PHASE2/PHASE3	UNKNOWN	A Single Intravitreal Injection of rAAV2-ND4 for the Treatment of Leber’s Hereditary Optic Neuropathy
NCT02064569	PHASE1/PHASE2	COMPLETED	Safety Evaluation of Gene Therapy in Leber Hereditary Optic Neuropathy (LHON) Patients
NCT05293626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Gene Therapy Clinical Trial for the Treatment of Leber’s Hereditary Optic Neuropathy Associated With ND4 Mutations
NCT05820152	PHASE1/PHASE2	TERMINATED	Gene Therapy Clinical Trial for the Treatment of Leber’s Hereditary Optic Neuropathy Associated With ND1 Mutations
NCT01267422	Not specified	COMPLETED	Safety and Efficacy Study of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy (LHON)
NCT01803906	Not specified	ENROLLING_BY_INVITATION	Tissue Sample Study for Mitochondrial Disorders
NCT01892943	Not specified	COMPLETED	Leber Hereditary Optic Neuropathy (LHON) Historical Case Record Survey
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT03295071	Not specified	COMPLETED	REALITY LHON Registry
NCT03428178	Not specified	UNKNOWN	Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months
NCT03475173	Not specified	RECRUITING	New Non-invasive Modalities for Assessing Retinal Structure and Function
NCT03672968	Not specified	NO_LONGER_AVAILABLE	EAP_GS010_single Patient
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT06376279	Not specified	ENROLLING_BY_INVITATION	Genetic Diagnosis in Inborn Errors of Metabolism
NCT06682819	Not specified	RECRUITING	Metabolomics Analysis According to the Retinal Nerve Fiber Layer in Patients With NOHL Mutations (MétabOCT)
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01834079	PHASE1/PHASE2	UNKNOWN	Study the Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Optic Nerve Disease
NCT04680143	PHASE1/PHASE2	COMPLETED	Systemic Erythropoietin Injection in Patients Having Optic Atrophy
NCT04580979	Not specified	COMPLETED	Natural History Study of FDXR Mutation-related Mitochondriopathy
NCT04594590	Not specified	COMPLETED	Natural History Study of SLC25A46 Mutation-related Mitochondriopathy
NCT04723160	Not specified	COMPLETED	Computer Aided Diagnosis of Multiple Eye Fundus Diseases From Color Fundus Photograph
NCT06390579	Not specified	COMPLETED	Building Research With Artificial Intelligence in Neuro-Ophthalmology