NDUFB9

Summary

NDUFB9 (NADH:ubiquinone oxidoreductase subunit B9, HGNC:7704) is a protein-coding gene on chromosome 8q24.13, encoding NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 (Q9Y6M9). Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed to be not involved in catalysis. It is a selective cancer dependency (DepMap: 50.1% of cell lines).

The protein encoded by this gene is a subunit of the mitochondrial oxidative phosphorylation complex I (nicotinamide adenine dinucleotide: ubiquinone oxidoreductase). Complex I is localized to the inner mitochondrial membrane and functions to dehydrogenate nicotinamide adenine dinucleotide and to shuttle electrons to coenzyme Q. Complex I deficiency is the most common defect found in oxidative phosphorylation disorders and results in a range of conditions, including lethal neonatal disease, hypertrophic cardiomyopathy, liver disease, and adult-onset neurodegenerative disorders. Pseudogenes of this gene are found on chromosomes five, seven and eight. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4715 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial complex I deficiency, nuclear type 24 (Moderate, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 126 total — 1 pathogenic
• Phenotypes (HPO): 41
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 50.1% of screened cell lines
• MANE Select transcript: NM_005005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7704
Approved symbol	NDUFB9
Name	NADH:ubiquinone oxidoreductase subunit B9
Location	8q24.13
Locus type	gene with protein product
Status	Approved
Aliases	B22, UQOR22, LYRM3
Ensembl gene	ENSG00000147684
Ensembl biotype	protein_coding
OMIM	601445
Entrez	4715

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 10 protein_coding, 5 nonsense_mediated_decay, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000276689, ENST00000517367, ENST00000517830, ENST00000518008, ENST00000518657, ENST00000522532, ENST00000524241, ENST00000606244, ENST00000676713, ENST00000677021, ENST00000677095, ENST00000677782, ENST00000677822, ENST00000677950, ENST00000678753, ENST00000678801, ENST00000901304, ENST00000901305, ENST00000928469, ENST00000928470, ENST00000928471, ENST00000928472

RefSeq mRNA: 4 — MANE Select: NM_005005 NM_001278645, NM_001278646, NM_001311168, NM_005005

CCDS: CCDS6352, CCDS83324

Canonical transcript exons

ENST00000276689 — 4 exons

Exon	Start	End
ENSE00000981319	124543087	124543279
ENSE00001240454	124539123	124539287
ENSE00002106234	124549761	124549979
ENSE00003636310	124547000	124547113

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 257.4733 / max 1445.8717, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90506	257.4733	1828

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	99.92	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.86	gold quality
kidney epithelium	UBERON:0004819	99.84	gold quality
tibialis anterior	UBERON:0001385	99.82	gold quality
myocardium	UBERON:0002349	99.82	gold quality
quadriceps femoris	UBERON:0001377	99.71	gold quality
ileal mucosa	UBERON:0000331	99.69	gold quality
vastus lateralis	UBERON:0001379	99.68	gold quality
body of tongue	UBERON:0011876	99.65	gold quality
deltoid	UBERON:0001476	99.64	gold quality
heart right ventricle	UBERON:0002080	99.62	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.61	gold quality
skeletal muscle tissue	UBERON:0001134	99.58	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.58	gold quality
gastrocnemius	UBERON:0001388	99.57	gold quality
upper arm skin	UBERON:0004263	99.57	gold quality
biceps brachii	UBERON:0001507	99.54	gold quality
apex of heart	UBERON:0002098	99.54	gold quality
renal medulla	UBERON:0000362	99.52	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.52	gold quality
cardiac ventricle	UBERON:0002082	99.51	gold quality
muscle tissue	UBERON:0002385	99.51	gold quality
pons	UBERON:0000988	99.50	gold quality
heart left ventricle	UBERON:0002084	99.50	gold quality
tongue	UBERON:0001723	99.47	gold quality
muscle of leg	UBERON:0001383	99.46	gold quality
superior vestibular nucleus	UBERON:0007227	99.44	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.42	gold quality
midbrain	UBERON:0001891	99.41	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	27.11
E-MTAB-10042	yes	13.33
E-CURD-122	yes	10.70
E-CURD-89	no	322.62
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 50.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• Mutant NDUFB9 is a new cause of complex I deficiency. (PMID:22200994)
• Down-Regulation of NDUFB9 Promotes Breast Cancer Cell Proliferation, Metastasis by Mediating Mitochondrial Metabolism. (PMID:26641458)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufb9	ENSDARG00000041314
mus_musculus	Ndufb9	ENSMUSG00000022354
rattus_norvegicus	Ndufb9	ENSRNOG00000085848
drosophila_melanogaster	ND-B22	FBGN0032511
caenorhabditis_elegans		WBGENE00015810

Protein

Protein identifiers

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 — Q9Y6M9 (reviewed: Q9Y6M9)

Alternative names: Complex I-B22, LYR motif-containing protein 3, NADH-ubiquinone oxidoreductase B22 subunit

All UniProt accessions (7): Q9Y6M9, A0A3B3IT57, A0A7I2V620, A0A7I2YQN0, E7EWZ0, E9PF49, E9PH64

UniProt curated annotations — full annotation on UniProt →

Function. Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed to be not 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. Mammalian complex I is composed of 45 different subunits.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Mitochondrial complex I deficiency, nuclear type 24 (MC1DN24) [MIM:618245] 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. MC1DN24 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 LYR family.

RefSeq proteins (4): NP_001265574, NP_001265575, NP_001298097, NP_004996* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008011	Complex1_LYR_dom	Domain
IPR033034	NDUFB9	Family
IPR045292	Complex1_LYR_NDUFB9_LYRM3	Domain

Pfam: PF05347

UniProt features (7 total): modified residue 2, sequence variant 2, initiator methionine 1, chain 1, region of interest 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-Q9Y6M9-F1	96.04	0.96

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 (2): 2, 85

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: 243 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, CREL_01, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, 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, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_OXIDATIVE_PHOSPHORYLATION

GO Biological Process (5): mitochondrial electron transport, NADH to ubiquinone (GO:0006120), sensory perception of sound (GO:0007605), 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
sensory perception of mechanical stimulus	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

2796 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDUFB9	NDUFB8	O95169	946
NDUFB9	NDUFB10	O96000	899
NDUFB9	NDUFS3	O75489	885
NDUFB9	UQCRC1	P31930	884
NDUFB9	NDUFA9	Q16795	871
NDUFB9	NDUFB4	O95168	869
NDUFB9	NDUFA11	Q86Y39	864
NDUFB9	NDUFV2	P19404	863
NDUFB9	NDUFB3	O43676	857
NDUFB9	NDUFS1	P28331	847
NDUFB9	UQCRFS1	P47985	836
NDUFB9	NDUFA6	P56556	835
NDUFB9	NDUFAB1	O14561	834
NDUFB9	NDUFB7	P17568	828
NDUFB9	NDUFS8	O00217	828

IntAct

144 interactions, top by confidence:

A	B	Type	Score
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
RHPN1	PODXL	psi-mi:“MI:0914”(association)	0.690
MAGEA11	NDUFB9	psi-mi:“MI:0915”(physical association)	0.670
HTT	NDUFB9	psi-mi:“MI:0915”(physical association)	0.670
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
NDUFB5	NDUFB3	psi-mi:“MI:0914”(association)	0.640
NDUFS7	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFA9	NDUFS4	psi-mi:“MI:0914”(association)	0.640
KLHL22	METTL15	psi-mi:“MI:0914”(association)	0.640

BioGRID (225): NDUFB9 (Two-hybrid), NDUFB9 (Affinity Capture-RNA), NDUFB9 (Affinity Capture-MS), NDUFB9 (Affinity Capture-MS), NDUFB9 (Affinity Capture-MS), NDUFB9 (Affinity Capture-MS), NDUFB9 (Affinity Capture-MS), NDUFB9 (Affinity Capture-MS), NDUFB9 (Two-hybrid), ATP5F1 (Co-fractionation), CLTC (Co-fractionation), LYRM5 (Co-fractionation), NDUFA12 (Co-fractionation), NDUFA2 (Co-fractionation), NDUFA6 (Co-fractionation)

ESM2 similar proteins: A3LNG8, A5DH70, A5DY61, A6ZZ82, A7TI92, A9UMQ3, B2RYU8, B3LFH4, B5FYC7, B5X5L2, B5XCZ6, B9WD12, C4R7H7, C4Y4R9, C5DEI4, C5DR94, C5FGP0, C5GY53, C5K1L1, C5MJD6, C7GKT0, C8Z651, G2TRM0, G2TRP8, O43089, O43325, O60068, Q02369, Q03429, Q0MQE8, Q0MQE9, Q0MQF0, Q0UIG9, Q503U1, Q54F42, Q54NR3, Q54T58, Q5A7N3, Q6BQH4, Q6CHK8

Diamond homologs: Q02369, Q0MQE8, Q0MQE9, Q0MQF0, Q54NR3, Q945M1, Q9CQJ8, Q9Y6M9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NDUFB9	“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 116 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	49.3×	9e-35
Respiratory electron transport	28	31.7×	2e-33
Aerobic respiration and respiratory electron transport	25	26.4×	2e-27
Mitochondrial protein degradation	7	9.5×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	20	69.6×	1e-30
proton motive force-driven mitochondrial ATP synthesis	23	58.8×	7e-33
aerobic respiration	23	55.3×	2e-32
mitochondrial respiratory chain complex I assembly	11	43.9×	1e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	56
Likely benign	39
Benign	14

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
65455	NM_005005.3(NDUFB9):c.191T>C (p.Leu64Pro)	Pathogenic

SpliceAI

2041 predictions. Top by Δscore:

Variant	Effect	Δscore
8:124539285:GAG:G	donor_gain	1.0000
8:124539286:AGGTA:A	donor_loss	1.0000
8:124539287:GGTAA:G	donor_loss	1.0000
8:124539289:T:A	donor_loss	1.0000
8:124543085:A:G	acceptor_gain	1.0000
8:124546996:ACAG:A	acceptor_loss	1.0000
8:124546997:CA:C	acceptor_loss	1.0000
8:124546998:A:AC	acceptor_loss	1.0000
8:124546998:A:AG	acceptor_gain	1.0000
8:124546999:G:GG	acceptor_gain	1.0000
8:124547109:GAGAG:G	donor_gain	1.0000
8:124547111:GAG:G	donor_gain	1.0000
8:124547114:G:GG	donor_gain	1.0000
8:124547115:T:G	donor_loss	1.0000
8:124553663:CACT:C	acceptor_gain	1.0000
8:124553666:T:C	acceptor_gain	1.0000
8:124553666:T:TC	acceptor_gain	1.0000
8:124553688:TGAAA:T	acceptor_loss	1.0000
8:124553691:AACT:A	acceptor_loss	1.0000
8:124553692:AC:A	acceptor_loss	1.0000
8:124553694:T:C	acceptor_loss	1.0000
8:124555900:CCAGG:C	acceptor_gain	1.0000
8:124555901:CAGGC:C	acceptor_gain	1.0000
8:124555903:GG:G	acceptor_gain	1.0000
8:124555905:C:CC	acceptor_gain	1.0000
8:124555908:C:CT	acceptor_gain	1.0000
8:124555909:A:T	acceptor_gain	1.0000
8:124555911:G:GC	acceptor_gain	1.0000
8:124555912:T:C	acceptor_gain	1.0000
8:124555912:T:TC	acceptor_gain	1.0000

AlphaMissense

1156 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:124539249:G:C	K21N	0.996
8:124539249:G:T	K21N	0.996
8:124539248:A:T	K21M	0.993
8:124543120:A:C	R45S	0.992
8:124543120:A:T	R45S	0.992
8:124547024:T:A	W107R	0.992
8:124547024:T:C	W107R	0.992
8:124543098:G:C	R38P	0.991
8:124539247:A:G	K21E	0.990
8:124543212:A:G	H76R	0.990
8:124549851:T:A	W167R	0.990
8:124549851:T:C	W167R	0.990
8:124539271:T:C	S29P	0.989
8:124543119:G:C	R45T	0.989
8:124543213:T:A	H76Q	0.989
8:124543213:T:G	H76Q	0.989
8:124547071:A:C	R122S	0.989
8:124547071:A:T	R122S	0.989
8:124543107:C:A	A41D	0.988
8:124543127:T:C	F48L	0.988
8:124543129:T:A	F48L	0.988
8:124543129:T:G	F48L	0.988
8:124543248:G:A	G88D	0.988
8:124539259:C:A	R25S	0.987
8:124539260:G:C	R25P	0.987
8:124547060:T:C	F119L	0.987
8:124547062:T:A	F119L	0.987
8:124547062:T:G	F119L	0.987
8:124543248:G:T	G88V	0.986
8:124543119:G:T	R45I	0.985

dbSNP variants (sampled 300 via entrez): RS1000146168 (8:124537855 T>C), RS1000198114 (8:124538149 T>C), RS1000589841 (8:124550473 C>T), RS1001251275 (8:124548567 A>G), RS1001498423 (8:124542989 C>T), RS1001608447 (8:124537434 G>A), RS1001641077 (8:124545946 G>A), RS1001695042 (8:124545707 T>A), RS1001887672 (8:124544501 T>G), RS1001979969 (8:124539953 A>G), RS1002433096 (8:124544560 C>T), RS1002581537 (8:124541271 T>C), RS1002644061 (8:124547545 G>A), RS1002918002 (8:124541551 A>T), RS1003733542 (8:124547437 T>C,G)

Disease associations

OMIM: gene MIM:601445 | disease phenotypes: MIM:618245

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex I deficiency, nuclear type 24	Moderate	Autosomal recessive
mitochondrial complex I deficiency	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Limited	AR

Mondo (2): mitochondrial complex I deficiency, nuclear type 24 (MONDO:0032628), mitochondrial complex I deficiency (MONDO:0100133)

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

HPO phenotypes

41 total (30 of 41 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:0001639	Hypertrophic cardiomyopathy
HP:0001943	Hypoglycemia
HP:0002013	Vomiting
HP:0002093	Respiratory insufficiency
HP:0002151	Increased circulating lactate concentration
HP:0002240	Hepatomegaly
HP:0002352	Leukoencephalopathy
HP:0002415	Leukodystrophy
HP:0002421	Poor head control
HP:0002490	Increased CSF lactate

GWAS associations

0 associations (top):

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), CHEMBL6067526 (SINGLE PROTEIN)

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

ChEMBL bioactivities

10 potent at pChembl≥5 of 20 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.61	Kd	244.3	nM	CHEMBL5653589
6.61	ED50	244.3	nM	CHEMBL5653589
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

9 with measured affinity, of 30 total; 5 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	2148850: Binding affinity to human NDUFB9 incubated for 45 mins by Kinobead based pull down assay	kd	0.2443	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
[(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

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects cotreatment, decreases expression	2
Atrazine	decreases expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	decreases expression	1
1-methyl-4-phenyl-2,3-dihydropyridinium	decreases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
Poly(amidoamine)	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Fluorouracil	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
Isoniazid	decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Dronabinol	decreases methylation	1
Tretinoin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases 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

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1YG	Abcam HeLa NDUFB9 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)