NDUFB3

Summary

NDUFB3 (NADH:ubiquinone oxidoreductase subunit B3, HGNC:7698) is a protein-coding gene on chromosome 2q33.1, encoding NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 (O43676). 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: 56.0% of cell lines).

This gene encodes an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which is the first enzyme in the electron transport chain of mitochondria. This protein localizes to the inner membrane of the mitochondrion as a single-pass membrane protein. Mutations in this gene contribute to mitochondrial complex 1 deficiency. Alternative splicing results in multiple transcript variants encoding the same protein. Humans have multiple pseudogenes of this gene.

Source: NCBI Gene 4709 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 51 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 42
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 56.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_002491

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7698
Approved symbol	NDUFB3
Name	NADH:ubiquinone oxidoreductase subunit B3
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	B12
Ensembl gene	ENSG00000119013
Ensembl biotype	protein_coding
OMIM	603839
Entrez	4709

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 21 protein_coding

ENST00000237889, ENST00000433898, ENST00000450023, ENST00000454214, ENST00000682325, ENST00000684175, ENST00000684420, ENST00000878930, ENST00000878931, ENST00000878932, ENST00000928296, ENST00000928297, ENST00000928298, ENST00000928299, ENST00000928300, ENST00000928301, ENST00000928302, ENST00000928303, ENST00000928304, ENST00000953983, ENST00000953984

RefSeq mRNA: 2 — MANE Select: NM_002491 NM_001257102, NM_002491

CCDS: CCDS2336

Canonical transcript exons

ENST00000237889 — 3 exons

Exon	Start	End
ENSE00000803331	201078881	201079022
ENSE00001166962	201072001	201072059
ENSE00001755355	201085459	201085750

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.7168 / max 265.9175, expressed in 1799 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24603	18.5879	1794
24602	1.7619	858
24601	1.6318	1046
24600	1.5674	1059
24599	0.1678	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart left ventricle	UBERON:0002084	99.20	gold quality
right atrium auricular region	UBERON:0006631	99.20	gold quality
apex of heart	UBERON:0002098	99.18	gold quality
cardiac ventricle	UBERON:0002082	99.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.13	gold quality
mucosa of transverse colon	UBERON:0004991	99.10	gold quality
cardiac atrium	UBERON:0002081	99.06	gold quality
biceps brachii	UBERON:0001507	99.01	gold quality
heart right ventricle	UBERON:0002080	98.87	gold quality
gastrocnemius	UBERON:0001388	98.86	gold quality
heart	UBERON:0000948	98.85	gold quality
diaphragm	UBERON:0001103	98.83	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.81	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.78	gold quality
triceps brachii	UBERON:0001509	98.74	gold quality
rectum	UBERON:0001052	98.70	gold quality
islet of Langerhans	UBERON:0000006	98.62	gold quality
muscle of leg	UBERON:0001383	98.61	gold quality
muscle organ	UBERON:0001630	98.56	gold quality
skeletal muscle organ	UBERON:0014892	98.56	gold quality
gluteal muscle	UBERON:0002000	98.46	gold quality
left ventricle myocardium	UBERON:0006566	98.44	gold quality
right adrenal gland	UBERON:0001233	98.43	gold quality
vastus lateralis	UBERON:0001379	98.42	gold quality
quadriceps femoris	UBERON:0001377	98.38	gold quality
skeletal muscle tissue	UBERON:0001134	98.36	gold quality
right adrenal gland cortex	UBERON:0035827	98.35	gold quality
myocardium	UBERON:0002349	98.31	gold quality
metanephros cortex	UBERON:0010533	98.27	gold quality
muscle tissue	UBERON:0002385	98.17	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	31.37
E-ANND-3	yes	16.96
E-GEOD-100618	no	912.15
E-GEOD-81383	no	266.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting NDUFB3, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-1322	97.98	68.96	625
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-5192	96.89	63.35	879

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 56.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Recessive mutations in NDUFB3 cause complex I deficiency (PMID:22277967)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufb3	ENSDARG00000075709
mus_musculus	Ndufb3	ENSMUSG00000026032
rattus_norvegicus	Ndufb3	ENSRNOG00000011825
rattus_norvegicus	AABR07060996.1	ENSRNOG00000048888
rattus_norvegicus	Ndufb3l3	ENSRNOG00000063738
rattus_norvegicus		ENSRNOG00000085148
drosophila_melanogaster	ND-B12	FBGN0034645
caenorhabditis_elegans		WBGENE00007684

Protein

Protein identifiers

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 — O43676 (reviewed: O43676)

Alternative names: Complex I-B12, NADH-ubiquinone oxidoreductase B12 subunit

All UniProt accessions (2): O43676, C9JKQ2

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.

Post-translational modifications. Methylation at His residues by METTL9 enhances complex I-mediated mitochondrial respiration.

Disease relevance. Mitochondrial complex I deficiency, nuclear type 25 (MC1DN25) [MIM:618246] 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. MC1DN25 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 NDUFB3 subunit family.

RefSeq proteins (2): NP_001244031, NP_002482* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012576	NDUFB3	Family

Pfam: PF08122

UniProt features (14 total): modified residue 8, sequence variant 2, initiator methionine 1, chain 1, mutagenesis site 1, transmembrane region 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-O43676-F1	86.74	0.69

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 (8): 34, 2, 5, 7, 9, 23, 23, 34

Mutagenesis-validated functional residues (1):

Position	Phenotype
5–9	abolished histidine methylation by mettl9.

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: 339 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, MODULE_93, MODULE_77, MORF_RRM1, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, MORF_HDAC2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY

GO Biological Process (5): mitochondrial electron transport, NADH to ubiquinone (GO:0006120), aerobic respiration (GO:0009060), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), electron transport chain (GO:0022900), proton transmembrane transport (GO:1902600)

GO Molecular Function (1): NADH dehydrogenase (ubiquinone) activity (GO:0008137)

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
generation of precursor metabolites and energy	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
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

1864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDUFB3	NDUFB8	O95169	950
NDUFB3	NDUFB5	O43674	947
NDUFB3	NDUFB7	P17568	945
NDUFB3	NDUFA5	Q16718	924
NDUFB3	NDUFA2	O43678	920
NDUFB3	WARS1	P23381	893
NDUFB3	NDUFA6	P56556	892
NDUFB3	NDUFS6	O75380	891
NDUFB3	NDUFC1	O43677	870
NDUFB3	NDUFV1	P49821	866
NDUFB3	NDUFB9	Q9Y6M9	857
NDUFB3	NDUFS1	P28331	853
NDUFB3	NDUFAB1	O14561	851
NDUFB3	NDUFB2	O95178	846
NDUFB3	NDUFA7	O95182	833

IntAct

115 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
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
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFA13	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFA9	NDUFS4	psi-mi:“MI:0914”(association)	0.640
NDUFS7	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFA9	NDUFS8	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
NDUFA8	NDUFS8	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
BTNL3	FAM171A2	psi-mi:“MI:0914”(association)	0.530
FUT1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
GALNT6	NDUFS4	psi-mi:“MI:0914”(association)	0.530
DNAJC30	NDUFS8	psi-mi:“MI:0914”(association)	0.530
NDUFC2	NDUFS4	psi-mi:“MI:0914”(association)	0.530
FUT1	NDUFS4	psi-mi:“MI:0914”(association)	0.530
PRRT2	NDUFB3	psi-mi:“MI:0914”(association)	0.530

BioGRID (165): NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0E4AVP3, A2ZBV1, B3EWG3, B3EWG5, B3EWG6, C5DGV3, G2TRQ6, G2TRR8, J7M799, O17389, O36029, O43676, O94724, P01094, P09442, P0CU45, P0CU46, P0CU48, P0CU49, P0CU50, P16547, P21298, P22238, P30287, P37219, P37220, Q08245, Q08655, Q09802, Q0MQD1, Q0MQD2, Q10195, Q16143, Q2PFW6, Q39846, Q4X212, Q53JF7, Q58676, Q63754, Q6FKB4

Diamond homologs: O43676, Q02365, Q0MQD0, Q0MQD1, Q0MQD2, Q9CQZ6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NDUFB3	“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 118 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	22	47.3×	6e-30
Respiratory electron transport	22	27.2×	3e-24
Aerobic respiration and respiratory electron transport	22	25.3×	1e-23

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	17	58.0×	4e-24
proton motive force-driven mitochondrial ATP synthesis	21	52.7×	1e-28
aerobic respiration	20	47.2×	2e-26
mitochondrial respiratory chain complex I assembly	10	39.1×	9e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	24
Likely benign	7
Benign	8

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1698952	NM_002491.3(NDUFB3):c.117del (p.Gly40_Leu41insTer)	Pathogenic
520909	NM_002491.3(NDUFB3):c.200del (p.Phe67fs)	Pathogenic
1678606	NM_002491.3(NDUFB3):c.61C>T (p.Gln21Ter)	Likely pathogenic
253348	GRCh37/hg19 2q33.1(chr2:201949918-201950495)x1	Likely pathogenic
809137	NM_002491.3(NDUFB3):c.201del (p.Phe68fs)	Likely pathogenic

SpliceAI

474 predictions. Top by Δscore:

Variant	Effect	Δscore
2:201072028:T:G	donor_gain	1.0000
2:201078878:C:G	acceptor_gain	1.0000
2:201078879:A:AG	acceptor_gain	1.0000
2:201078880:G:GC	acceptor_gain	1.0000
2:201078880:GA:G	acceptor_gain	1.0000
2:201078880:GAC:G	acceptor_gain	1.0000
2:201078880:GACA:G	acceptor_gain	1.0000
2:201078880:GACAT:G	acceptor_gain	1.0000
2:201079001:GGC:G	donor_gain	1.0000
2:201079002:GC:G	donor_gain	1.0000
2:201079003:C:G	donor_gain	1.0000
2:201079018:GGCCG:G	donor_gain	1.0000
2:201079019:GCCG:G	donor_gain	1.0000
2:201079019:GCCGG:G	donor_gain	1.0000
2:201079020:CCGG:C	donor_loss	1.0000
2:201079022:GGTA:G	donor_loss	1.0000
2:201079023:G:C	donor_loss	1.0000
2:201079023:G:GG	donor_gain	1.0000
2:201079024:T:G	donor_loss	1.0000
2:201079030:GAAT:G	donor_gain	1.0000
2:201079033:T:G	donor_gain	1.0000
2:201079033:T:TG	donor_gain	1.0000
2:201085455:CTAGC:C	acceptor_loss	1.0000
2:201085456:TAGCA:T	acceptor_loss	1.0000
2:201085457:A:AG	acceptor_gain	1.0000
2:201085457:AGC:A	acceptor_loss	1.0000
2:201085458:G:GA	acceptor_gain	1.0000
2:201085458:GC:G	acceptor_gain	1.0000
2:201085458:GCA:G	acceptor_gain	1.0000
2:201071609:CCTG:C	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000034784 (2:201084207 G>A), RS1000086841 (2:201083985 G>A), RS1000639014 (2:201074349 A>C,T), RS1000996284 (2:201083014 C>T), RS1001047267 (2:201071998 C>A,T), RS1001139573 (2:201075883 A>G), RS1001297671 (2:201078219 G>A), RS1001299105 (2:201076231 GCTGTAATCCCA>G), RS1001351376 (2:201075819 A>G), RS1001452986 (2:201072616 G>A), RS1002256875 (2:201083887 G>A), RS1002262539 (2:201075459 G>A,C), RS1002309438 (2:201083554 C>G,T), RS1002345845 (2:201077570 G>C,T), RS1002445498 (2:201082187 C>G)

Disease associations

OMIM: gene MIM:603839 | disease phenotypes: MIM:618246

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex I deficiency, nuclear type 25	Definitive	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	Definitive	AR

Mondo (2): mitochondrial complex I deficiency, nuclear type 25 (MONDO:0032629), mitochondrial complex I deficiency (MONDO:0100133)

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

HPO phenotypes

42 total (30 of 42 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:0001622	Premature birth
HP:0001639	Hypertrophic cardiomyopathy
HP:0001943	Hypoglycemia
HP:0002013	Vomiting
HP:0002093	Respiratory insufficiency
HP:0002240	Hepatomegaly
HP:0002352	Leukoencephalopathy
HP:0002415	Leukodystrophy
HP:0002421	Poor head control
HP:0002490	Increased CSF lactate

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003842_21	Breast cancer (estrogen-receptor negative)	1.000000e-06
GCST003845_22	Breast cancer	7.000000e-08

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 (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

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, affects cotreatment	4
Acetaminophen	affects cotreatment, decreases expression, increases expression	3
Air Pollutants	affects expression, increases abundance, decreases expression	3
Valproic Acid	affects expression, decreases methylation, increases expression	3
Cyclosporine	decreases expression	3
bisphenol A	affects expression, decreases expression	2
sodium arsenite	increases expression	2
Doxorubicin	affects expression, increases expression	2
Lead	affects expression, increases expression	2
Lipopolysaccharides	affects response to substance, affects cotreatment, decreases expression, affects expression	2
Rotenone	increases expression	2
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
azoxystrobin	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
corosolic acid	decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
picoxystrobin	increases expression	1
Vorinostat	increases expression	1
Diuron	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Isoniazid	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)

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)