NDUFS1

Summary

NDUFS1 (NADH:ubiquinone oxidoreductase core subunit S1, HGNC:7707) is a protein-coding gene on chromosome 2q33.3, encoding NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (P28331). 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: 37.3% of cell lines).

The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized. Mutations in this gene are associated with complex I deficiency. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4719 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 505 total — 15 pathogenic, 30 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 37.3% of screened cell lines
• MANE Select transcript: NM_005006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7707
Approved symbol	NDUFS1
Name	NADH:ubiquinone oxidoreductase core subunit S1
Location	2q33.3
Locus type	gene with protein product
Status	Approved
Aliases	CI-75k
Ensembl gene	ENSG00000023228
Ensembl biotype	protein_coding
OMIM	157655
Entrez	4719

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 31 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000233190, ENST00000423725, ENST00000432169, ENST00000440274, ENST00000449699, ENST00000454195, ENST00000456284, ENST00000457011, ENST00000498520, ENST00000903700, ENST00000903701, ENST00000903702, ENST00000903703, ENST00000903704, ENST00000903705, ENST00000903706, ENST00000903707, ENST00000903708, ENST00000903709, ENST00000938122, ENST00000938123, ENST00000938124, ENST00000948898, ENST00000948899, ENST00000948900, ENST00000948901, ENST00000948902, ENST00000948903, ENST00000948904, ENST00000948905, ENST00000948906, ENST00000948907, ENST00000948908

RefSeq mRNA: 5 — MANE Select: NM_005006 NM_001199981, NM_001199982, NM_001199983, NM_001199984, NM_005006

CCDS: CCDS2366, CCDS56162, CCDS56163, CCDS56164

Canonical transcript exons

ENST00000233190 — 19 exons

Exon	Start	End
ENSE00000469822	206142686	206142831
ENSE00000469824	206138485	206138614
ENSE00000784947	206126539	206126611
ENSE00000784948	206126710	206126844
ENSE00000784949	206127797	206127972
ENSE00000784951	206132945	206133105
ENSE00000784953	206141941	206142069
ENSE00000784955	206144018	206144132
ENSE00000784956	206144892	206145026
ENSE00000784957	206146903	206147088
ENSE00000784958	206147531	206147661
ENSE00000796659	206152419	206152510
ENSE00001366685	206159341	206159444
ENSE00001840375	206114817	206124276
ENSE00003559678	206149818	206149925
ENSE00003598955	206153618	206153682
ENSE00003625672	206130088	206130242
ENSE00003657299	206149020	206149096
ENSE00003678234	206147753	206147834

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 98.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.3791 / max 664.7939, expressed in 1812 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33353	46.7844	1811
33354	1.2637	869
33352	1.1954	705
33351	0.1355	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	98.69	gold quality
skeletal muscle tissue	UBERON:0001134	98.35	gold quality
adrenal tissue	UBERON:0018303	98.31	gold quality
skeletal muscle organ	UBERON:0014892	98.10	gold quality
muscle of leg	UBERON:0001383	98.09	gold quality
gastrocnemius	UBERON:0001388	98.05	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.00	gold quality
heart left ventricle	UBERON:0002084	97.81	gold quality
apex of heart	UBERON:0002098	97.42	gold quality
right atrium auricular region	UBERON:0006631	97.11	gold quality
muscle tissue	UBERON:0002385	96.83	gold quality
islet of Langerhans	UBERON:0000006	96.81	gold quality
heart	UBERON:0000948	96.79	gold quality
rectum	UBERON:0001052	96.66	gold quality
right adrenal gland	UBERON:0001233	96.33	gold quality
adrenal gland	UBERON:0002369	96.09	gold quality
right adrenal gland cortex	UBERON:0035827	95.97	gold quality
duodenum	UBERON:0002114	95.96	gold quality
left adrenal gland	UBERON:0001234	95.94	gold quality
calcaneal tendon	UBERON:0003701	95.29	gold quality
left adrenal gland cortex	UBERON:0035825	95.23	gold quality
colonic epithelium	UBERON:0000397	94.93	gold quality
tonsil	UBERON:0002372	94.56	gold quality
smooth muscle tissue	UBERON:0001135	94.44	gold quality
superior frontal gyrus	UBERON:0002661	94.43	gold quality
prefrontal cortex	UBERON:0000451	94.30	gold quality
liver	UBERON:0002107	94.24	gold quality
adult mammalian kidney	UBERON:0000082	94.14	gold quality
kidney	UBERON:0002113	94.04	gold quality
ventricular zone	UBERON:0003053	93.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	1375.62
E-MTAB-6386	no	160.13
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting NDUFS1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-32-3P	99.36	68.20	2517

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 37.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 21)

• A patient with Leigh syndrome had a mutation in the NDUFS1 protein of Complex I of the Respiratory Chain. Identifying nuclear mutations will help us understand how molecular defects can lead to complex I deficiency. (PMID:15824269)
• mutations in the NDUFS1 and NDUFS4 genes of complex I cause dysfunction in cellular oxidative metabolism (PMID:16478720)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• Mutations in electron Transport Complex I is associated with Leber hereditary optic neuropathy failing to compensate for impaired oxidative phosphorylation. (PMID:19836344)
• report 3 patients with low residual complex I activity who displayed novel mutations in the NDUFS1 gene. One mutation introduces a premature stop codon, 3 mutations cause a substitution of amino acids and another mutation a deletion of one amino acid. (PMID:20382551)
• data suggest that gamma oscillations are especially energy demanding and require both high complex I expression and strong functional performance of mitochondria. (PMID:21183487)
• homozygous c.1783A>G (p.Thr595Ala) mutation in NDUFS1 in two inbred siblings with isolated complex I deficiency associated to a progressive cavitating leukoencephalopathy (PMID:21203893)
• The peripheral leukocyte oxidative phosphorylation enzyme activity assay was found to be a reliable method for the diagnosis of mitochondrial diseases. (PMID:21540367)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Some mutations in NDUFS1 cause a milder phenotype with a more benign course despite the initial decompensation phase. Homozygosity for the c.755A > G missense mutation may correlate with the milder clinical picture in the patient. (PMID:24952175)
• NDUFS1 may confer susceptibility to schizophrenia in male subjects, acting as a causative factor for the severity of negative symptoms in schizophrenia. (PMID:25354934)
• The presented clinical courses of NDUFV1 and NDUFS1 mutation-based complex I deficiencies are characterized by leukoencephalopathy or early death and expand the already heterogeneous phenotypic spectrum. (PMID:25615419)
• 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)
• Loss of FOXRED1, coupled with protein, choline and/or folate-deficient diets results in the depletion of glutathione, the dysregulation of nitric oxide metabolism and the peroxynitrite-mediated inactivation of complex I. (PMID:26235939)
• High NDUFS1 expression is associated with cognitive impairment in lung cancer. (PMID:26987334)
• Results show that NDUFS1 protein and mRNA levels are down-regulated in lung neoplasm and correlate with poor overall survival. (PMID:27516145)
• MDM2 directly binds and sequesters NDUFS1, preventing its mitochondrial localization and ultimately causing complex I and supercomplex destabilization and inefficiency of oxidative phosphorylation. (PMID:30879903)
• The biallelic mutations in NDUFS1 led to a decreased stability of the entire N-module of electron transport complex I and disrupted the electron transfer between two iron-sulfur clusters. (PMID:31557978)
• Down regulation of NDUFS1 is involved in the progression of parenteral-nutrition-associated liver disease by increasing Oxidative stress. (PMID:36402252)
• PHB2 promotes colorectal cancer cell proliferation and tumorigenesis through NDUFS1-mediated oxidative phosphorylation. (PMID:36658121)
• Association between NDUFS1 from urinary extracellular vesicles and decreased differential renal function in children with ureteropelvic junction obstruction. (PMID:38720274)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufs1	ENSDARG00000028546
mus_musculus	Ndufs1	ENSMUSG00000025968
rattus_norvegicus	Ndufs1	ENSRNOG00000011849
drosophila_melanogaster	ND-75	FBGN0017566
caenorhabditis_elegans		WBGENE00021562

Paralogs (2): CIAO3 (ENSG00000103245), NARF (ENSG00000141562)

Protein

Protein identifiers

NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial — P28331 (reviewed: P28331)

Alternative names: Complex I-75kD

All UniProt accessions (5): B4DJ81, C9JPQ5, E5KRK5, P28331, F8WDL5

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 catalysing the entry and efficient transfer of electrons within complex I. Plays a key role in the assembly and stability of complex I and participates in the association of complex I with ubiquinol-cytochrome reductase complex (Complex III) to form supercomplexes.

Subunit / interactions. Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits. This is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. Complex I associates with ubiquinol-cytochrome reductase complex (Complex III) to form supercomplexes. Interacts with MDM2. Interacts with AKAP1.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Mitochondrial complex I deficiency, nuclear type 5 (MC1DN5) [MIM:618226] 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. MC1DN5 transmission pattern is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 [2Fe-2S] cluster per subunit. Binds 2 [4Fe-4S] clusters per subunit.

Similarity. Belongs to the complex I 75 kDa subunit family.

Isoforms (5)

UniProt ID	Names	Canonical?
P28331-1	1	yes
P28331-2	2
P28331-3	3
P28331-4	4
P28331-5	5

RefSeq proteins (5): NP_001186910, NP_001186911, NP_001186912, NP_001186913, NP_004997* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000283	NADH_UbQ_OxRdtase_75kDa_su_CS	Conserved_site
IPR001041	2Fe-2S_ferredoxin-type	Domain
IPR006656	Mopterin_OxRdtase	Domain
IPR006963	Mopterin_OxRdtase_4Fe-4S_dom	Domain
IPR010228	NADH_UbQ_OxRdtase_Gsu	Family
IPR015405	NDUFS1-like_C	Domain
IPR019574	NADH_UbQ_OxRdtase_Gsu_4Fe4S-bd	Domain
IPR036010	2Fe-2S_ferredoxin-like_sf	Homologous_superfamily
IPR050123
IPR054351	NADH_UbQ_OxRdtase_ferredoxin	Domain

Pfam: PF00384, PF09326, PF10588, PF13510, PF22117, PF22151

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (92 total): helix 27, strand 19, binding site 12, turn 10, sequence variant 6, splice variant 5, modified residue 4, sequence conflict 4, domain 3, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

7 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
5XTD	ELECTRON MICROSCOPY	3.7
5XTH	ELECTRON MICROSCOPY	3.9
5XTI	ELECTRON MICROSCOPY	17.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28331-F1	92.97	0.90

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 (12): 128; 131; 137; 176; 179; 182; 226; 64; 75; 78; 92; 124

Post-translational modifications (4): 84, 467, 499, 709

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-611105	Respiratory electron transport
R-HSA-6799198	Complex I biogenesis
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 354 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, MORF_MBD4, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, MORF_RAD21, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, COUP_01, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP

GO Biological Process (7): mitochondrial electron transport, NADH to ubiquinone (GO:0006120), aerobic respiration (GO:0009060), mitochondrial respiratory chain complex I assembly (GO:0032981), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), cellular respiration (GO:0045333), ATP synthesis coupled electron transport (GO:0042773), proton transmembrane transport (GO:1902600)

GO Molecular Function (9): NADH dehydrogenase (ubiquinone) activity (GO:0008137), electron transfer activity (GO:0009055), oxidoreductase activity, acting on NAD(P)H (GO:0016651), metal ion binding (GO:0046872), 2 iron, 2 sulfur cluster binding (GO:0051537), 4 iron, 4 sulfur cluster binding (GO:0051539), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (7): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759), respiratory chain complex I (GO:0045271), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-4 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
oxidative phosphorylation	2
iron-sulfur cluster binding	2
mitochondrial envelope	2
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
cellular respiration	1
NADH dehydrogenase complex assembly	1
mitochondrial respiratory chain complex assembly	1
proton motive force-driven ATP synthesis	1
energy derivation by oxidation of organic compounds	1
respiratory electron transport chain	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
cation binding	1
binding	1
catalytic activity	1
metal cluster binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
organelle envelope lumen	1
intracellular organelle lumen	1
NADH dehydrogenase complex	1
respiratory chain complex	1
transmembrane transporter complex	1
cellular anatomical structure	1
organelle membrane	1

Protein interactions and networks

STRING

3164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDUFS1	NDUFV2	P19404	999
NDUFS1	NDUFV1	P49821	999
NDUFS1	NDUFS2	O75306	998
NDUFS1	NDUFS3	O75489	996
NDUFS1	NDUFS7	O75251	995
NDUFS1	NDUFS8	O00217	994
NDUFS1	NDUFA2	O43678	989
NDUFS1	NDUFS6	O75380	985
NDUFS1	NDUFS4	O43181	984
NDUFS1	NDUFA5	Q16718	946
NDUFS1	NDUFA9	Q16795	934
NDUFS1	NDUFV3	P56181	931
NDUFS1	NDUFA6	P56556	920
NDUFS1	NDUFS5	O43920	903
NDUFS1	NDUFA12	Q9UI09	885

IntAct

207 interactions, top by confidence:

A	B	Type	Score
NDUFAF1	NDUFS3	psi-mi:“MI:0914”(association)	0.790
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
CFTR	ESYT2	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
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
HOXC9	AHCYL1	psi-mi:“MI:0914”(association)	0.640
NDUFA9	NDUFS4	psi-mi:“MI:0914”(association)	0.640
NDUFS5	NDUFS8	psi-mi:“MI:0914”(association)	0.530
NDUFA9	NDUFS8	psi-mi:“MI:0914”(association)	0.530
NDUFA8	NDUFS8	psi-mi:“MI:0914”(association)	0.530
NDUFV2	NDUFS8	psi-mi:“MI:0914”(association)	0.530
PML	NDUFA2	psi-mi:“MI:0914”(association)	0.530
DNAJC30	NDUFS8	psi-mi:“MI:0914”(association)	0.530

BioGRID (528): NDUFS1 (Affinity Capture-MS), NDUFS1 (Affinity Capture-MS), NDUFS1 (Affinity Capture-MS), NDUFS1 (Affinity Capture-MS), AFG3L2 (Co-fractionation), ATP1A1 (Co-fractionation), ATP6V0D1 (Co-fractionation), CLTC (Co-fractionation), GNB2 (Co-fractionation), COX2 (Co-fractionation), ND1 (Co-fractionation), NDUFA9 (Co-fractionation), NDUFS1 (Co-fractionation), NDUFS1 (Co-fractionation), NDUFS1 (Co-fractionation)

ESM2 similar proteins: A2TLM1, A2ZLS4, B4G0F3, B8BKI7, B9N1F9, B9SQI7, C6JS30, O04059, O04397, P0CB67, P0CB68, P0DPI2, P13653, P15690, P19356, P22907, P28331, P31166, P41345, P46225, P47968, P49085, Q0MQG1, Q0MQG2, Q27601, Q2QNF7, Q2R483, Q39161, Q41578, Q42850, Q42997, Q43654, Q4R6K9, Q5NAY4, Q66HF1, Q69QJ7, Q6AV34, Q6EI12, Q7XKF3, Q8W3D9

Diamond homologs: A0A1D8PU51, I3R634, O21241, O52683, P0CB67, P0CB68, P15690, P24918, P28331, P29915, P39458, P42434, P59962, P61159, P73448, P86203, P9WIV8, P9WIV9, Q06457, Q0MQG1, Q0MQG2, Q1RKD2, Q2LCP5, Q34312, Q37373, Q43644, Q46508, Q4R6K9, Q4UK22, Q66HF1, Q68VV2, Q6LXQ1, Q91VD9, Q92G92, Q94511, Q9FGI6, Q9XAR0, Q9ZCF6, D7AF63, F1SVN3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
metformin	“down-regulates activity”	NDUFS1	“chemical inhibition”
NDUFS1	“form complex”	“NADH-ubiquinone oxidoreductase-Mitochondrial respiratory chain complex I”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 189 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	25	32.6×	2e-29
Respiratory electron transport	27	20.2×	7e-26
Aerobic respiration and respiratory electron transport	25	17.4×	3e-22
Mitochondrial protein degradation	15	13.5×	4e-11
Complex IV assembly	7	12.6×	1e-04
Mitochondrial protein import	6	7.9×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	21	46.8×	6e-28
proton motive force-driven mitochondrial ATP synthesis	23	37.6×	6e-28
aerobic respiration	22	33.9×	1e-25
mitochondrial respiratory chain complex I assembly	12	30.6×	8e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	30
Uncertain significance	203
Likely benign	122
Benign	65

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
14230	NM_005006.7(NDUFS1):c.666_668del (p.Ile223del)	Pathogenic
14231	NM_005006.7(NDUFS1):c.755A>G (p.Asp252Gly)	Pathogenic
1451930	NM_005006.7(NDUFS1):c.673dup (p.Ile225fs)	Pathogenic
1453980	NM_005006.7(NDUFS1):c.1070del (p.Leu357fs)	Pathogenic
1897450	NM_005006.7(NDUFS1):c.29_42del (p.Ala9_Leu10insTer)	Pathogenic
2049239	NM_005006.7(NDUFS1):c.1255C>T (p.Arg419Ter)	Pathogenic
214780	NM_005006.7(NDUFS1):c.699_700del (p.Lys234fs)	Pathogenic
2708405	NM_005006.7(NDUFS1):c.1564C>T (p.Gln522Ter)	Pathogenic
2895765	NM_005006.7(NDUFS1):c.1963C>T (p.Arg655Ter)	Pathogenic
3254827	NM_005006.7(NDUFS1):c.1880_1881del (p.Leu626_Ser627insTer)	Pathogenic
3681358	NM_005006.7(NDUFS1):c.1589_1596del (p.Tyr530fs)	Pathogenic
3896664	NM_005006.7(NDUFS1):c.2029C>T (p.Gln677Ter)	Pathogenic
50922	NM_005006.7(NDUFS1):c.1855G>A (p.Asp619Asn)	Pathogenic
50923	NM_005006.7(NDUFS1):c.1669C>T (p.Arg557Ter)	Pathogenic
626277	NM_005006.7(NDUFS1):c.64C>T (p.Arg22Ter)	Pathogenic
1193648	NM_005006.7(NDUFS1):c.62-2A>G	Likely pathogenic
1324785	NM_005006.7(NDUFS1):c.1810C>T (p.Gln604Ter)	Likely pathogenic
1506164	NM_005006.7(NDUFS1):c.338+1G>A	Likely pathogenic
1804014	NM_005006.7(NDUFS1):c.988-2A>C	Likely pathogenic
1879518	NM_005006.7(NDUFS1):c.228G>T (p.Arg76Ser)	Likely pathogenic
190449	NM_005006.7(NDUFS1):c.758T>G (p.Val253Gly)	Likely pathogenic
214775	NM_005006.7(NDUFS1):c.1696A>T (p.Ile566Phe)	Likely pathogenic
214777	NM_005006.7(NDUFS1):c.1800G>C (p.Glu600Asp)	Likely pathogenic
214779	NM_005006.7(NDUFS1):c.589ACA[1] (p.Thr198del)	Likely pathogenic
214784	NM_005006.7(NDUFS1):c.1727G>A (p.Gly576Glu)	Likely pathogenic
214785	NM_005006.7(NDUFS1):c.2107G>A (p.Ala703Thr)	Likely pathogenic
2430648	NM_005006.7(NDUFS1):c.631_633del (p.Glu211del)	Likely pathogenic
2630234	NM_005006.7(NDUFS1):c.1773_1774dup (p.Lys592fs)	Likely pathogenic
2690651	NM_005006.7(NDUFS1):c.1119dup (p.Thr374fs)	Likely pathogenic
2769975	NM_005006.7(NDUFS1):c.61+1_61+3del	Likely pathogenic

SpliceAI

2928 predictions. Top by Δscore:

Variant	Effect	Δscore
2:206124129:TGCAC:T	donor_gain	1.0000
2:206124133:C:CT	donor_gain	1.0000
2:206124134:T:TT	donor_gain	1.0000
2:206124153:T:C	donor_gain	1.0000
2:206126534:CAT:C	donor_loss	1.0000
2:206126535:ATACC:A	donor_loss	1.0000
2:206126608:CTAG:C	acceptor_gain	1.0000
2:206126609:TAG:T	acceptor_gain	1.0000
2:206126610:AG:A	acceptor_gain	1.0000
2:206126610:AGCT:A	acceptor_loss	1.0000
2:206126611:GCTG:G	acceptor_loss	1.0000
2:206126612:C:CC	acceptor_gain	1.0000
2:206126612:CTGCA:C	acceptor_loss	1.0000
2:206126615:C:CT	acceptor_gain	1.0000
2:206126617:C:CT	acceptor_gain	1.0000
2:206126618:A:T	acceptor_gain	1.0000
2:206126704:TGTTA:T	donor_loss	1.0000
2:206126705:GTTAC:G	donor_loss	1.0000
2:206126706:TTA:T	donor_loss	1.0000
2:206126707:TA:T	donor_loss	1.0000
2:206126708:A:G	donor_loss	1.0000
2:206126709:C:G	donor_loss	1.0000
2:206126843:ATCTA:A	acceptor_loss	1.0000
2:206126845:C:CC	acceptor_gain	1.0000
2:206126851:CA:C	acceptor_gain	1.0000
2:206126852:A:C	acceptor_gain	1.0000
2:206126856:C:CT	acceptor_gain	1.0000
2:206126857:A:T	acceptor_gain	1.0000
2:206126864:C:CT	acceptor_gain	1.0000
2:206126864:C:T	acceptor_gain	1.0000

AlphaMissense

4773 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:206144911:A:G	W285R	1.000
2:206144911:A:T	W285R	1.000
2:206146911:C:A	W243C	1.000
2:206146911:C:G	W243C	1.000
2:206146913:A:G	W243R	1.000
2:206146913:A:T	W243R	1.000
2:206146954:C:T	G229D	1.000
2:206146955:C:G	G229R	1.000
2:206146962:G:C	C226W	1.000
2:206146963:C:T	C226Y	1.000
2:206146964:A:G	C226R	1.000
2:206146977:A:C	N221K	1.000
2:206146977:A:T	N221K	1.000
2:206147531:C:A	R184M	1.000
2:206147536:G:C	C182W	1.000
2:206147537:C:T	C182Y	1.000
2:206147538:A:G	C182R	1.000
2:206147545:A:C	C179W	1.000
2:206147546:C:A	C179F	1.000
2:206147546:C:G	C179S	1.000
2:206147546:C:T	C179Y	1.000
2:206147547:A:G	C179R	1.000
2:206147547:A:T	C179S	1.000
2:206147552:A:T	I177K	1.000
2:206147554:A:C	C176W	1.000
2:206147555:C:T	C176Y	1.000
2:206147556:A:G	C176R	1.000
2:206147558:C:A	R175I	1.000
2:206147558:C:G	R175T	1.000
2:206147753:C:A	Q140H	1.000

dbSNP variants (sampled 300 via entrez): RS1000083891 (2:206147370 C>A,G), RS1000160517 (2:206119430 GAC>G), RS1000178025 (2:206132469 C>G,T), RS1000178857 (2:206159395 C>A,G,T), RS1000240465 (2:206153020 A>C), RS1000284923 (2:206128481 G>C,T), RS1000350980 (2:206121805 G>A), RS1000401060 (2:206119037 G>C), RS1000507583 (2:206130995 A>G,T), RS1000507712 (2:206129334 C>T), RS1000572614 (2:206135825 T>C), RS1000613734 (2:206124822 G>A,C), RS1000765969 (2:206130637 G>C), RS1000797106 (2:206125092 C>CA,CT), RS1000820671 (2:206117243 A>G)

Disease associations

OMIM: gene MIM:157655 | disease phenotypes: MIM:618226, MIM:252010, MIM:256000, MIM:540000

GenCC curated gene-disease

Disease	Classification	Inheritance
Leigh syndrome	Definitive	Autosomal recessive
mitochondrial complex I deficiency, nuclear type 5	Definitive	Autosomal recessive
Leigh syndrome with leukodystrophy	Supportive	Autosomal recessive
mitochondrial complex I deficiency	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 (7): mitochondrial complex I deficiency, nuclear type 5 (MONDO:0032610), mitochondrial complex I deficiency, nuclear type 1 (MONDO:0100224), Leigh syndrome (MONDO:0009723), mitochondrial complex I deficiency (MONDO:0100133), MELAS syndrome (MONDO:0010789), mitochondrial disease (MONDO:0044970), (MONDO:0016815)

Orphanet (4): Leigh syndrome (Orphanet:506), Isolated complex I deficiency (Orphanet:2609), MELAS (Orphanet:550), Mitochondrial disease (Orphanet:68380)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000114	Proximal tubulopathy
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000543	Optic disc pallor
HP:0000602	Ophthalmoplegia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000737	Irritability
HP:0000817	Reduced eye contact
HP:0000819	Diabetes mellitus
HP:0001138	Optic neuropathy
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005951_45	Body mass index	1.000000e-09
GCST006148_3	Frontotemporal dementia with GRN mutation	1.000000e-06
GCST007565_91	Morning person	1.000000e-13
GCST007576_291	Chronotype	1.000000e-13
GCST011494_17	Daytime nap	4.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008328	chronotype measurement
EFO:0007828	daytime rest measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D007888	Leigh Disease	C10.228.140.163.100.412; C16.320.565.189.412; C16.320.565.202.810.444; C18.452.132.100.412; C18.452.648.189.412; C18.452.648.202.810.444; C18.452.660.520
D017241	MELAS Syndrome	C05.651.460.620.520; C10.228.140.163.100.535; C10.228.140.300.275.500; C10.668.491.500.500.500; C14.907.253.329.500; C16.320.565.189.535; C18.452.132.100.535; C18.452.648.189.535; C18.452.660.560.620.520
C537475	Mitochondrial complex I deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363065 (PROTEIN COMPLEX), CHEMBL6066925 (SINGLE PROTEIN)

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

ChEMBL bioactivities

12 potent at pChembl≥5 of 22 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.12	Kd	764.8	nM	CHEMBL3752910
6.12	ED50	764.8	nM	CHEMBL3752910
6.06	IC50	870	nM	R-(+)-MARMIN-6’-UNDECANOATE
6.04	IC50	920	nM	R-(+)-MARMIN-6’-LINOLEATE
6.02	Kd	959.1	nM	CHEMBL5653589
6.02	ED50	959.1	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	2148852: Binding affinity to human NDUFS1 incubated for 45 mins by Kinobead based pull down assay	kd	0.7648	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	2148852: Binding affinity to human NDUFS1 incubated for 45 mins by Kinobead based pull down assay	kd	0.9591	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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	4
Acetaminophen	affects cotreatment, decreases expression	3
bisphenol A	increases expression, decreases expression	2
bisphenol S	affects cotreatment, decreases expression, increases expression	2
Resveratrol	affects cotreatment, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation, affects expression	2
Hydrogen Peroxide	affects cotreatment, affects reaction, decreases expression, decreases reaction	2
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance, affects expression	2
Rotenone	decreases reaction, decreases expression	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
PQQ Cofactor	decreases expression, decreases reaction, increases response to substance	2
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases expression, increases oxidation, increases abundance, affects cotreatment	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
alpha-naphthoflavone	decreases expression, decreases reaction	1
arsenite	affects binding, decreases reaction	1
ochratoxin A	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	1
epigallocatechin gallate	affects reaction, decreases expression, decreases reaction, affects cotreatment	1
gallocatechol	affects cotreatment, affects reaction, decreases expression, decreases reaction	1
epicatechin gallate	affects cotreatment, affects reaction, decreases expression, decreases reaction	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases expression, decreases reaction	1
bisphenol B	increases expression	1
abrine	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

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

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 induced pluripotent stem cell, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C6Q5	IUFi002-A	Induced pluripotent stem cell	Female
CVCL_D1P4	Abcam K-562 NDUFS1 KO	Cancer cell line	Female
CVCL_D2KP	Abcam Raji NDUFS1 KO	Cancer cell line	Male
CVCL_EQ47	8328	Finite cell line	Male
CVCL_WQ06	Abcam Jurkat NDUFS1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01831934	PHASE4	COMPLETED	Responses to Influenza Vaccine in Patients With Mitochondrial Disorders (MELAS)
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT01721733	PHASE2	COMPLETED	Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
NCT02352896	PHASE2	COMPLETED	Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome
NCT03747328	PHASE2	WITHDRAWN	ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
NCT06843811	PHASE2	ENROLLING_BY_INVITATION	Sirolimus for Leigh Syndrome
NCT06990984	PHASE2	NOT_YET_RECRUITING	A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS)
NCT00068913	PHASE2	UNKNOWN	Evaluating the Effectiveness of a Dichloroacetate in MELAS Syndrome
NCT00887562	PHASE2	COMPLETED	Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes
NCT01603446	PHASE2	COMPLETED	L-arginine Therapy on Endothelium-dependent Vasodilation & Mitochondrial Metabolism in MELAS Syndrome
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04475549	PHASE2	TERMINATED	Phase 2a Study of IW-6463 in Adults Diagnosed With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT06644534	PHASE2	RECRUITING	A Study to Assess TTI-0102 vs Placebo in MELAS Patients
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03056209	PHASE1	COMPLETED	Safety, Tolerability and Pharmacokinetic Study of KL1333 in Healthy Male Volunteers
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT03952234	PHASE1	COMPLETED	L-Citrulline Dose Finding Safety Study in MELAS
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels