NDUFB10

Summary

NDUFB10 (NADH:ubiquinone oxidoreductase subunit B10, HGNC:7696) is a protein-coding gene on chromosome 16p13.3, encoding NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 (O96000). Accessory subunit that is involved in the functional assembly of the mitochondrial respiratory chain complex I. It is a selective cancer dependency (DepMap: 61.4% 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. Implicated in nuclear type mitochondrial complex I deficiency 35.

Source: NCBI Gene 4716 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 90 total — 1 likely-pathogenic
• Phenotypes (HPO): 51
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 61.4% of screened cell lines
• MANE Select transcript: NM_004548

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7696
Approved symbol	NDUFB10
Name	NADH:ubiquinone oxidoreductase subunit B10
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PDSW
Ensembl gene	ENSG00000140990
Ensembl biotype	protein_coding
OMIM	603843
Entrez	4716

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000268668, ENST00000543683, ENST00000565031, ENST00000569148, ENST00000570172, ENST00000909021, ENST00000926882, ENST00000926883, ENST00000926884

RefSeq mRNA: 1 — MANE Select: NM_004548 NM_004548

CCDS: CCDS10451

Canonical transcript exons

ENST00000268668 — 4 exons

Exon	Start	End
ENSE00000945996	1961153	1961291
ENSE00001118727	1959538	1959754
ENSE00001326404	1961797	1961975
ENSE00001363304	1961497	1961636

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 159.4051 / max 933.4848, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152139	151.6421	1828
152140	7.7630	1727

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.87	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.75	gold quality
myocardium	UBERON:0002349	99.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.48	gold quality
quadriceps femoris	UBERON:0001377	99.45	gold quality
tibialis anterior	UBERON:0001385	99.45	gold quality
apex of heart	UBERON:0002098	99.44	gold quality
vastus lateralis	UBERON:0001379	99.42	gold quality
cardiac ventricle	UBERON:0002082	99.39	gold quality
heart left ventricle	UBERON:0002084	99.39	gold quality
gastrocnemius	UBERON:0001388	99.37	gold quality
heart right ventricle	UBERON:0002080	99.36	gold quality
muscle of leg	UBERON:0001383	99.32	gold quality
cardiac atrium	UBERON:0002081	99.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.24	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.23	gold quality
body of tongue	UBERON:0011876	99.23	gold quality
right atrium auricular region	UBERON:0006631	99.22	gold quality
ileal mucosa	UBERON:0000331	99.21	gold quality
biceps brachii	UBERON:0001507	99.20	gold quality
skeletal muscle tissue	UBERON:0001134	99.19	gold quality
heart	UBERON:0000948	99.16	gold quality
deltoid	UBERON:0001476	99.15	gold quality
muscle tissue	UBERON:0002385	99.07	gold quality
mucosa of transverse colon	UBERON:0004991	99.07	gold quality
upper arm skin	UBERON:0004263	98.95	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.81	gold quality
kidney epithelium	UBERON:0004819	98.78	gold quality
parotid gland	UBERON:0001831	98.72	gold quality
transverse colon	UBERON:0001157	98.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10596	no	754.21
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 61.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• Src kinase inhibition led to a decrease in mitochondrial respiration via a specific decrease in complex I activities which is associated with a lower phosphorylation of the complex I subunit NDUFB10. (PMID:22321370)
• findings indicate that mutations in NDUFB10 are a novel cause of complex I deficiency associated with a late stage assembly defect and emphasize the role of intermembrane space proteins for the efficient assembly of complex I. (PMID:28040730)
• Loss of respiratory complex I subunit NDUFB10 affects complex I assembly and supercomplex formation. (PMID:36952351)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufb10	ENSDARG00000028889
mus_musculus	Ndufb10	ENSMUSG00000040048
rattus_norvegicus	Ndufb10	ENSRNOG00000014568
drosophila_melanogaster	ND-PDSW	FBGN0021967
caenorhabditis_elegans	ndub-10	WBGENE00010326

Protein

Protein identifiers

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 — O96000 (reviewed: O96000)

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

All UniProt accessions (4): O96000, A8K761, H3BPJ9, H3BV16

UniProt curated annotations — full annotation on UniProt →

Function. Accessory subunit that is involved in the functional assembly of the mitochondrial respiratory chain complex I. Complex I has an NADH dehydrogenase activity with ubiquinone as an immediate electron acceptor and mediates the transfer of electrons from NADH to the respiratory chain.

Subunit / interactions. Complex I is composed of 45 different subunits. Interacts with CHCHD4; assists NDUFB10 oxidation, folding and import into mitochondrion.

Subcellular location. Mitochondrion inner membrane.

Post-translational modifications. The formation of intramolecular disulfide bonds is assisted by CHCHD4 and ensures folding, import into the mitochondrion and is required for the function in mitochondrial respiratory chain complex I assembly.

Disease relevance. Mitochondrial complex I deficiency, nuclear type 35 (MC1DN35) [MIM:619003] 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. MC1DN35 transmission pattern is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the complex I NDUFB10 subunit family.

Isoforms (2)

UniProt ID	Names	Canonical?
O96000-1	1	yes
O96000-2	2

RefSeq proteins (1): NP_004539* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019377	NADH_UbQ_OxRdtase_su10	Family
IPR039993	NDUFB10	Family

Pfam: PF10249

UniProt features (4 total): chain 1, modified residue 1, splice variant 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-O96000-F1	90.95	0.75

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): 145

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: 281 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, MODULE_77, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, 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_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_ATP_BIOSYNTHETIC_PROCESS, GOBP_OXIDATIVE_PHOSPHORYLATION, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_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

2296 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDUFB10	NDUFA10	O95299	981
NDUFB10	NDUFB4	O95168	980
NDUFB10	NDUFB5	O43674	966
NDUFB10	NDUFA7	O95182	935
NDUFB10	NDUFB11	Q9NX14	922
NDUFB10	NDUFB2	O95178	917
NDUFB10	NDUFB9	Q9Y6M9	899
NDUFB10	NDUFB1	O75438	892
NDUFB10	NDUFA9	Q16795	881
NDUFB10	NDUFA8	P51970	880
NDUFB10	NDUFA2	O43678	869
NDUFB10	NDUFB6	O95139	855
NDUFB10	NDUFB7	P17568	828
NDUFB10	NDUFS2	O75306	810
NDUFB10	NDUFS1	P28331	810

IntAct

137 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
FAM9B	NDUFB10	psi-mi:“MI:0915”(physical association)	0.720
NDUFB10	FAM9B	psi-mi:“MI:0915”(physical association)	0.720
NDUFB10	HTT	psi-mi:“MI:0915”(physical association)	0.670
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFB5	NDUFB3	psi-mi:“MI:0914”(association)	0.640
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
PIK3R2	IRS4	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 (218): FAM9B (Two-hybrid), NDUFB10 (Affinity Capture-MS), ATP5O (Co-fractionation), BCAP31 (Co-fractionation), MRPS7 (Co-fractionation), NDUFB10 (Co-fractionation), NDUFB10 (Co-fractionation), NDUFB10 (Co-fractionation), NDUFS1 (Co-fractionation), NDUFV2 (Co-fractionation), TPM1 (Co-fractionation), TPM2 (Co-fractionation), TPM3 (Co-fractionation), TPM4 (Co-fractionation), NDUFB10 (Synthetic Lethality)

ESM2 similar proteins: A5DUN2, A6ZMQ6, B3LM82, B4JT39, B5RTE0, C4Y2J3, C4YIM0, C5DT65, C5E268, C5M6H7, C7GRF7, C8ZF59, G2TRJ8, G2TRP6, O42921, O60200, O75012, O94581, O96000, P00429, P0CC01, P0CC02, P21976, P56391, P90789, Q01519, Q02772, Q04341, Q0MQF2, Q0MQF3, Q17Q91, Q1K8U2, Q28GG4, Q2M2S5, Q2TAP8, Q3E731, Q3E7A9, Q3E846, Q462Q7, Q4R374

Diamond homologs: O96000, P0CC01, P0CC02, Q02373, Q0MQF2, Q0MQF3, Q1HPL8, Q9DCS9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NDUFB10	“form complex”	“NADH-ubiquinone oxidoreductase-Mitochondrial respiratory chain complex I”	binding
TFEB	“up-regulates quantity by expression”	NDUFB10	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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	24	57.6×	4e-35
Respiratory electron transport	24	33.1×	7e-29
Aerobic respiration and respiratory electron transport	23	29.5×	2e-26
Mitochondrial protein degradation	6	9.9×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	17	70.9×	9e-26
proton motive force-driven mitochondrial ATP synthesis	20	61.2×	1e-28
aerobic respiration	20	57.6×	3e-28
mitochondrial respiratory chain complex I assembly	12	57.4×	1e-16

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	56
Likely benign	22
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
873018	NM_004548.3(NDUFB10):c.131-442G>C	Likely pathogenic

SpliceAI

709 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1959752:GAG:G	donor_gain	1.0000
16:1959753:AGGTA:A	donor_loss	1.0000
16:1959754:GGT:G	donor_loss	1.0000
16:1959755:GTACG:G	donor_loss	1.0000
16:1961151:A:AG	acceptor_gain	1.0000
16:1961152:G:GA	acceptor_gain	1.0000
16:1961152:GA:G	acceptor_gain	1.0000
16:1961152:GAA:G	acceptor_gain	1.0000
16:1961152:GAAT:G	acceptor_gain	1.0000
16:1961152:GAATT:G	acceptor_gain	1.0000
16:1961259:G:GG	donor_gain	1.0000
16:1961287:GACTA:G	donor_gain	1.0000
16:1961292:G:GG	donor_gain	1.0000
16:1961296:G:GG	donor_gain	1.0000
16:1961309:G:GT	donor_gain	1.0000
16:1961492:A:AG	acceptor_gain	1.0000
16:1961494:CA:C	acceptor_loss	1.0000
16:1961495:A:AG	acceptor_gain	1.0000
16:1961496:G:GT	acceptor_gain	1.0000
16:1961496:GC:G	acceptor_gain	1.0000
16:1961496:GCAA:G	acceptor_gain	1.0000
16:1961496:GCAAA:G	acceptor_gain	1.0000
16:1961591:G:GT	donor_gain	1.0000
16:1961591:G:T	donor_gain	1.0000
16:1961621:GCC:G	donor_gain	1.0000
16:1961630:G:GT	donor_gain	1.0000
16:1961637:G:GG	donor_gain	1.0000
16:1959750:GAGAG:G	donor_gain	0.9900
16:1959751:AGAG:A	donor_gain	0.9900
16:1959752:GAGG:G	donor_gain	0.9900

AlphaMissense

1153 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1961266:G:C	A82P	0.992
16:1961277:G:C	Q85H	0.991
16:1961277:G:T	Q85H	0.991
16:1961535:G:C	R103P	0.990
16:1961278:T:A	W86R	0.989
16:1961278:T:C	W86R	0.989
16:1961280:G:C	W86C	0.989
16:1961280:G:T	W86C	0.989
16:1961286:G:C	R88S	0.989
16:1961286:G:T	R88S	0.989
16:1961582:T:A	C119S	0.989
16:1961583:G:C	C119S	0.989
16:1961233:T:A	C71S	0.988
16:1961234:G:C	C71S	0.988
16:1961254:T:A	C78S	0.988
16:1961255:G:C	C78S	0.988
16:1961287:G:C	D89H	0.988
16:1961843:A:C	K152N	0.987
16:1961843:A:T	K152N	0.987
16:1961834:C:G	C149W	0.986
16:1961546:T:A	C107S	0.984
16:1961547:G:C	C107S	0.984
16:1961288:A:C	D89A	0.983
16:1961584:T:G	C119W	0.983
16:1961288:A:T	D89V	0.982
16:1961254:T:C	C78R	0.981
16:1961265:A:C	E81D	0.980
16:1961265:A:T	E81D	0.980
16:1961267:C:A	A82D	0.979
16:1961583:G:A	C119Y	0.979

dbSNP variants (sampled 300 via entrez): RS1000045293 (16:1959342 C>G,T), RS1000110516 (16:1957631 G>A,T), RS1000541451 (16:1960018 T>C), RS1000846292 (16:1959866 C>G,T), RS1001008825 (16:1961652 A>C,G), RS1001045688 (16:1960123 A>C,G,T), RS1001230793 (16:1959933 C>G), RS1001537032 (16:1961599 G>A), RS1001670060 (16:1958213 C>T), RS1002127108 (16:1960591 C>T), RS1002183147 (16:1958020 T>G), RS1003126500 (16:1961356 G>A,T), RS1003354644 (16:1957807 G>A), RS1003764073 (16:1959039 A>C), RS1003814723 (16:1957715 G>A,C)

Disease associations

OMIM: gene MIM:603843 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial disease	Strong	Autosomal recessive
mitochondrial complex I deficiency	Supportive	Autosomal recessive
mitochondrial complex 1 deficiency, nuclear type 35	Limited	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Moderate	AR

Mondo (3): mitochondrial complex I deficiency (MONDO:0100133), mitochondrial complex 1 deficiency, nuclear type 35 (MONDO:0033560), mitochondrial disease (MONDO:0044970)

Orphanet (1): Isolated complex I deficiency (Orphanet:2609)

HPO phenotypes

51 total (30 of 51 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:0000543	Optic disc pallor
HP:0000618	Blindness
HP:0000639	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:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001638	Cardiomyopathy
HP:0001639	Hypertrophic cardiomyopathy
HP:0001790	Nonimmune hydrops fetalis
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia
HP:0002013	Vomiting
HP:0002089	Pulmonary hypoplasia
HP:0002092	Pulmonary arterial hypertension
HP:0002093	Respiratory insufficiency
HP:0002240	Hepatomegaly

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010796_5218	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537475	Mitochondrial complex I deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363065 (PROTEIN COMPLEX), CHEMBL6066985 (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
7.00	Kd	99.87	nM	CHEMBL5653589
7.00	ED50	99.87	nM	CHEMBL5653589
6.06	IC50	870	nM	R-(+)-MARMIN-6’-UNDECANOATE
6.04	IC50	920	nM	R-(+)-MARMIN-6’-LINOLEATE
5.93	Kd	1167	nM	CHEMBL3752910
5.93	ED50	1167	nM	CHEMBL3752910
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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148845: Binding affinity to human NDUFB10 incubated for 45 mins by Kinobead based pull down assay	kd	0.0999	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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148845: Binding affinity to human NDUFB10 incubated for 45 mins by Kinobead based pull down assay	kd	1.1667	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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, decreases expression	4
bisphenol A	increases expression, decreases expression, decreases methylation	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
Acetaminophen	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	increases expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	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

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TA16	HAP1 NDUFB10 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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)
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
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
NCT02909400	PHASE2	COMPLETED	The KHENERGY 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
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
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
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)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
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
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01642056	PHASE1/PHASE2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT03384420	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD in Pediatric Patients With Pearson Syndrome
NCT06051448	PHASE1/PHASE2	COMPLETED	Promoting Resilience in Stress Management (PRISM) and Clinical-focused Narrative (CFN) Pilot in Adults With Primary Mitochondrial Disease (PMD).
NCT01252979	EARLY_PHASE1	COMPLETED	Ketones & Mitochondrial Heteroplasmy
NCT00786539	Not specified	COMPLETED	Mitochondria Inborn Errors of Metabolism and ANT Defects in Mitochondria Diseases
NCT00829270	Not specified	COMPLETED	Economic and Medical Evaluation of the Whole Mitochondrial DNA Screening by Surveyor and Mitochips Techniques
NCT00831948	Not specified	UNKNOWN	Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.
NCT01001585	Not specified	TERMINATED	Anesthetic Effects in Mitochondrial Disease
NCT01148550	Not specified	SUSPENDED	Longitudinal Study of Mitochondrial Hepatopathies