NDUFA3

Summary

NDUFA3 (NADH:ubiquinone oxidoreductase subunit A3, HGNC:7686) is a protein-coding gene on chromosome 19q13.42, encoding NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 (O95167). Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. It is a selective cancer dependency (DepMap: 13.3% of cell lines).

Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be involved in mitochondrial electron transport, NADH to ubiquinone and proton motive force-driven mitochondrial ATP synthesis. Located in mitochondrial inner membrane. Part of respiratory chain complex I.

Source: NCBI Gene 4696 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Leigh syndrome (Limited, GenCC)
• Clinical variants (ClinVar): 28 total — 2 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 13.3% of screened cell lines
• MANE Select transcript: NM_004542

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7686
Approved symbol	NDUFA3
Name	NADH:ubiquinone oxidoreductase subunit A3
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	B9
Ensembl gene	ENSG00000170906
Ensembl biotype	protein_coding
OMIM	603832
Entrez	4696

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000303553, ENST00000391762, ENST00000391763, ENST00000391764, ENST00000417903, ENST00000419113, ENST00000420296, ENST00000422029, ENST00000451517, ENST00000471292, ENST00000480713, ENST00000482960, ENST00000484103, ENST00000485876, ENST00000878191

RefSeq mRNA: 1 — MANE Select: NM_004542 NM_004542

CCDS: CCDS12877

Canonical transcript exons

ENST00000485876 — 4 exons

Exon	Start	End
ENSE00001872133	54106811	54107568
ENSE00003465178	54102855	54102888
ENSE00003527842	54105934	54106011
ENSE00003567016	54103114	54103188

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 125.4269 / max 656.8442, expressed in 1826 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177464	121.2405	1826
177463	2.5357	1357
177466	1.1434	504
177465	0.5073	282

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primary visual cortex	UBERON:0002436	99.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.57	gold quality
superior frontal gyrus	UBERON:0002661	99.54	gold quality
apex of heart	UBERON:0002098	99.46	gold quality
putamen	UBERON:0001874	99.40	gold quality
prefrontal cortex	UBERON:0000451	99.38	gold quality
caudate nucleus	UBERON:0001873	99.36	gold quality
nucleus accumbens	UBERON:0001882	99.36	gold quality
substantia nigra	UBERON:0002038	99.31	gold quality
temporal lobe	UBERON:0001871	99.30	gold quality
amygdala	UBERON:0001876	99.30	gold quality
right atrium auricular region	UBERON:0006631	99.29	gold quality
heart left ventricle	UBERON:0002084	99.28	gold quality
Ammon’s horn	UBERON:0001954	99.26	gold quality
pituitary gland	UBERON:0000007	99.24	gold quality
adenohypophysis	UBERON:0002196	99.23	gold quality
cortex of kidney	UBERON:0001225	99.22	gold quality
anterior cingulate cortex	UBERON:0009835	99.22	gold quality
hypothalamus	UBERON:0001898	99.20	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.20	gold quality
frontal cortex	UBERON:0001870	99.18	gold quality
mucosa of transverse colon	UBERON:0004991	99.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.17	gold quality
cerebral cortex	UBERON:0000956	99.16	gold quality
skeletal muscle tissue	UBERON:0001134	99.12	gold quality
gastrocnemius	UBERON:0001388	99.10	gold quality
brain	UBERON:0000955	99.09	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.08	gold quality
right frontal lobe	UBERON:0002810	99.07	gold quality
adult mammalian kidney	UBERON:0000082	99.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	19.52
E-CURD-89	no	88.68

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• NDUFA3, NDUFA5 and NDUFA12 supernumerary subunits are necessary for complex I activity and biogenesis. (PMID:24717771)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufa3	ENSDARG00000041400
mus_musculus	Ndufa3	ENSMUSG00000035674
rattus_norvegicus	LOC103690298	ENSRNOG00000029868
rattus_norvegicus	Ndufa3-ps1	ENSRNOG00000030778
rattus_norvegicus	Ndufa3-ps3	ENSRNOG00000050514
rattus_norvegicus	Ndufa3	ENSRNOG00000060293

Protein

Protein identifiers

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 — O95167 (reviewed: O95167)

Alternative names: Complex I-B9, NADH-ubiquinone oxidoreductase B9 subunit

All UniProt accessions (10): O95167, A8MUI2, A8MVM8, A8MYJ8, F2Z2C6, H7C0D7, H7C2R1, Q6FGG4, S4R3I5, S4R3T6

UniProt curated annotations — full annotation on UniProt →

Function. Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.

Subunit / interactions. Complex I is composed of 45 different subunits.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the complex I NDUFA3 subunit family.

RefSeq proteins (1): NP_004533* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026626	NDUFA3	Family

Pfam: PF14987

UniProt features (6 total): initiator methionine 1, chain 1, transmembrane region 1, region of interest 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9I4I	ELECTRON MICROSCOPY	2.63
9TI4	ELECTRON MICROSCOPY	2.66
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-O95167-F1	96.78	0.98

Functional residue map

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

Post-translational modifications (1): 2

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: 173 (showing top): RRAGTTGT_UNKNOWN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MODULE_77, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, RACCACAR_AML_Q6, TGACCTY_ERR1_Q2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, COUP_01, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, MARTINEZ_RB1_TARGETS_UP, GOBP_ATP_BIOSYNTHETIC_PROCESS

GO Biological Process (4): mitochondrial electron transport, NADH to ubiquinone (GO:0006120), aerobic respiration (GO:0009060), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), proton transmembrane transport (GO:1902600)

GO Molecular Function (2): NADH dehydrogenase (ubiquinone) activity (GO:0008137), protein binding (GO:0005515)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), 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
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
cellular respiration	1
mitochondrion	1
oxidative phosphorylation	1
proton motive force-driven ATP synthesis	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
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
NADH dehydrogenase complex	1
respiratory chain complex	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDUFA3	NDUFA2	O43678	937
NDUFA3	NDUFA8	P51970	927
NDUFA3	NDUFA13	Q9P0J0	904
NDUFA3	NDUFA7	O95182	770
NDUFA3	NDUFA1	O15239	757
NDUFA3	NDUFB11	Q9NX14	753
NDUFA3	NDUFA11	Q86Y39	734
NDUFA3	NDUFS7	O75251	727
NDUFA3	NDUFB3	O43676	720
NDUFA3	NDUFB7	P17568	718
NDUFA3	NDUFV1	P49821	712
NDUFA3	NDUFS8	O00217	699
NDUFA3	COXFA4	O00483	691
NDUFA3	NDUFB6	O95139	687
NDUFA3	TIMMDC1	Q9NPL8	679

IntAct

130 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
NDUFA3	MMGT1	psi-mi:“MI:0915”(physical association)	0.670
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFA13	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFA9	NDUFS4	psi-mi:“MI:0914”(association)	0.640
NDUFA3	LEPROTL1	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	EBP	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	ERG28	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	TMX2	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	CRB3	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	GOLT1A	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	TMEM242	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	TM4SF19	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	MUC1	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	TMEM101	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (111): NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS)

ESM2 similar proteins: A0A096LP01, A3LP48, A3LQD9, A5DLM7, A6SAY2, A6ZLK2, A7EJE5, A7TMN2, B3LMP9, B9WD58, C4YPM0, C5DRK2, C5E381, C7GMW8, D3UF10, G2TRJ9, O22912, O74383, O95167, P0DN34, P19173, P20609, P20610, P26310, P38341, P48306, Q02365, Q02371, Q0MQ94, Q0MQ95, Q0MQ96, Q2KP58, Q2V2Q3, Q42841, Q59LP6, Q59QC6, Q6BL60, Q6C5S0, Q6CHT7, Q752G2

Diamond homologs: O95167, Q02371, Q0MQ94, Q0MQ95, Q0MQ96, Q9CQ91

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NDUFA3	“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 100 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	20	50.1×	2e-27
Respiratory electron transport	19	27.4×	1e-20
Aerobic respiration and respiratory electron transport	19	25.5×	3e-20

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	15	59.8×	3e-21
mitochondrial respiratory chain complex I assembly	11	50.2×	2e-14
proton motive force-driven mitochondrial ATP synthesis	17	49.7×	3e-22
aerobic respiration	17	46.8×	5e-22

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	18
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2579241	GRCh38/hg38 19q13.42(chr19:54106667-54131817)x1	Pathogenic
2579242	GRCh38/hg38 19q13.42(chr19:54105500-54126715)x1	Pathogenic

SpliceAI

1341 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54102885:GCGA:G	donor_gain	1.0000
19:54102886:CGA:C	donor_gain	1.0000
19:54102886:CGAG:C	donor_loss	1.0000
19:54102887:GA:G	donor_gain	1.0000
19:54102887:GAG:G	donor_gain	1.0000
19:54102888:AG:A	donor_loss	1.0000
19:54102889:G:GG	donor_gain	1.0000
19:54102889:GTA:G	donor_loss	1.0000
19:54103189:G:GG	donor_gain	1.0000
19:54103191:GC:G	donor_gain	1.0000
19:54103193:G:GG	donor_gain	1.0000
19:54105932:A:AG	acceptor_gain	1.0000
19:54105933:G:GA	acceptor_gain	1.0000
19:54105933:GCT:G	acceptor_gain	1.0000
19:54105933:GCTGT:G	acceptor_gain	1.0000
19:54106008:CCAGG:C	donor_loss	1.0000
19:54106009:CAGG:C	donor_loss	1.0000
19:54106012:G:GA	donor_loss	1.0000
19:54106013:T:G	donor_loss	1.0000
19:54107169:TC:T	acceptor_loss	1.0000
19:54107170:C:CA	acceptor_loss	1.0000
19:54107170:C:CC	acceptor_gain	1.0000
19:54108321:CTCA:C	donor_loss	1.0000
19:54108322:TCAC:T	donor_loss	1.0000
19:54108323:CA:C	donor_loss	1.0000
19:54108324:ACCT:A	donor_gain	1.0000
19:54108325:CCTC:C	donor_gain	1.0000
19:54102884:TGCGA:T	donor_gain	0.9900
19:54102885:GCGAG:G	donor_gain	0.9900
19:54103108:CTTCA:C	acceptor_loss	0.9900

AlphaMissense

545 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54105954:A:C	S36R	0.991
19:54105956:C:A	S36R	0.991
19:54105956:C:G	S36R	0.991
19:54106885:T:A	W80R	0.991
19:54106885:T:C	W80R	0.991
19:54106887:G:C	W80C	0.991
19:54106887:G:T	W80C	0.991
19:54103174:T:A	V24D	0.988
19:54103177:T:A	V25D	0.987
19:54103140:T:A	W13R	0.981
19:54103140:T:C	W13R	0.981
19:54103182:G:C	G27R	0.981
19:54105934:C:A	A29D	0.980
19:54106005:T:C	Y53H	0.978
19:54103142:G:C	W13C	0.977
19:54103142:G:T	W13C	0.977
19:54105937:T:A	V30E	0.977
19:54103162:T:A	V20D	0.975
19:54103180:G:A	G26E	0.975
19:54106852:C:G	H69D	0.974
19:54103137:G:C	A12P	0.973
19:54103165:T:A	V21E	0.973
19:54103179:G:A	G26R	0.973
19:54103179:G:C	G26R	0.973
19:54106814:C:A	P56H	0.973
19:54106819:C:A	R58S	0.972
19:54106870:G:C	G75R	0.972
19:54106829:G:T	G61V	0.971
19:54103138:C:A	A12D	0.967
19:54103186:T:G	L28R	0.967

dbSNP variants (sampled 300 via entrez): RS1000987201 (19:54102419 A>G), RS1001018340 (19:54102644 C>T), RS1001396359 (19:54107967 C>T), RS1004928554 (19:54104881 G>C), RS1005601392 (19:54106912 C>T), RS1006153147 (19:54106703 C>A,T), RS1007041322 (19:54102092 C>A,T), RS1007858225 (19:54106298 C>T), RS1007895449 (19:54103477 C>T), RS1009890159 (19:54107930 C>G), RS1010024013 (19:54107655 C>G,T), RS1011798227 (19:54105171 T>C), RS1011970854 (19:54105654 C>T), RS1012157237 (19:54105626 C>T), RS1013799254 (19:54102665 C>A)

Disease associations

OMIM: gene MIM:603832 | disease phenotypes: MIM:600138

GenCC curated gene-disease

Disease	Classification	Inheritance
Leigh syndrome	Limited	Autosomal recessive

Mondo (2): retinitis pigmentosa 11 (MONDO:0010828), Leigh syndrome (MONDO:0009723)

Orphanet (1): Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

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
C563991	Retinitis Pigmentosa 11 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2363065 (PROTEIN COMPLEX)

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

ChEMBL bioactivities

8 potent at pChembl≥5 of 18 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.06	IC50	870	nM	R-(+)-MARMIN-6’-UNDECANOATE
6.04	IC50	920	nM	R-(+)-MARMIN-6’-LINOLEATE
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

8 with measured affinity, of 28 total; 4 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
[(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
[(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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Valproic Acid	affects cotreatment, increases expression, increases methylation	3
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
ginger extract	decreases expression, increases abundance	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
ochratoxin A	increases expression	1
chloropicrin	increases expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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)
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01780168	Not specified	RECRUITING	The NIH MINI Study: Metabolism, Infection, and Immunity in Inborn Errors of Metabolism
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01803906	Not specified	ENROLLING_BY_INVITATION	Tissue Sample Study for Mitochondrial Disorders
NCT03137355	Not specified	RECRUITING	The International Registry for Leigh Syndrome
NCT05277363	Not specified	WITHDRAWN	A Study of the Natural Course of SURF1 Deficiency
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT06967831	Not specified	RECRUITING	Drug Repurposing for Mitochondrial Disorders Using iPSCs Derived Neural Cells
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT04805658	Not specified	ACTIVE_NOT_RECRUITING	Natural History Study of Retinitis Pigmentosa Type 11