NDUFB8

Summary

NDUFB8 (NADH:ubiquinone oxidoreductase subunit B8, HGNC:7703) is a protein-coding gene on chromosome 10q24.31, encoding NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial (O95169). 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: 38.7% 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 32. Biomarker of Alzheimer’s disease and Parkinson’s disease.

Source: NCBI Gene 4714 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial complex I deficiency, nuclear type 32 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 107 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 38.7% of screened cell lines
• MANE Select transcript: NM_005004

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7703
Approved symbol	NDUFB8
Name	NADH:ubiquinone oxidoreductase subunit B8
Location	10q24.31
Locus type	gene with protein product
Status	Approved
Aliases	ASHI, CI-ASHI
Ensembl gene	ENSG00000166136
Ensembl biotype	protein_coding
OMIM	602140
Entrez	4714

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000299166, ENST00000370320, ENST00000370322, ENST00000464651, ENST00000466088, ENST00000528425, ENST00000529437, ENST00000531189, ENST00000531418, ENST00000718301, ENST00000894511, ENST00000894512, ENST00000894513, ENST00000937695, ENST00000937696, ENST00000941273, ENST00000941274

RefSeq mRNA: 3 — MANE Select: NM_005004 NM_001284367, NM_001284368, NM_005004

CCDS: CCDS65916, CCDS65917, CCDS7497

Canonical transcript exons

ENST00000299166 — 5 exons

Exon	Start	End
ENSE00003497310	100529380	100529506
ENSE00003667825	100526975	100527074
ENSE00003681482	100526399	100526554
ENSE00004034701	100523740	100523929
ENSE00004034702	100529767	100529871

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.3800 / max 527.5345, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111062	78.2051	1827
205966	0.1749	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.89	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.71	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.62	gold quality
pons	UBERON:0000988	99.60	gold quality
choroid plexus epithelium	UBERON:0003911	99.57	gold quality
cervix squamous epithelium	UBERON:0006922	99.54	gold quality
middle temporal gyrus	UBERON:0002771	99.52	gold quality
superior vestibular nucleus	UBERON:0007227	99.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.51	gold quality
right frontal lobe	UBERON:0002810	99.50	gold quality
substantia nigra pars compacta	UBERON:0001965	99.49	gold quality
prefrontal cortex	UBERON:0000451	99.47	gold quality
amygdala	UBERON:0001876	99.46	gold quality
primary visual cortex	UBERON:0002436	99.46	gold quality
cingulate cortex	UBERON:0003027	99.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.44	gold quality
anterior cingulate cortex	UBERON:0009835	99.44	gold quality
apex of heart	UBERON:0002098	99.43	gold quality
occipital lobe	UBERON:0002021	99.42	gold quality
renal medulla	UBERON:0000362	99.41	gold quality
frontal cortex	UBERON:0001870	99.41	gold quality
temporal lobe	UBERON:0001871	99.41	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.41	gold quality
superior frontal gyrus	UBERON:0002661	99.41	gold quality
frontal lobe	UBERON:0016525	99.41	gold quality
parietal lobe	UBERON:0001872	99.39	gold quality
putamen	UBERON:0001874	99.39	gold quality
ventral tegmental area	UBERON:0002691	99.39	gold quality
postcentral gyrus	UBERON:0002581	99.37	gold quality
cerebral cortex	UBERON:0000956	99.36	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting NDUFB8, 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-4682	100.00	68.89	1258
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-3167	96.81	67.09	1236

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 38.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• Results describe PTEN and NDUFB8 aberrations in cervical cancer tissue. (PMID:17727244)
• We observed loss of NDUFB8 immunoreactivity in all patients with mutations affecting nuclear-encoding structural subunits and assembly factors, whilst only 3 of the 10 patients with mutations affecting mtDNA-encoded structural subunits showed loss of NDUFB8, confirmed by BN-PAGE analysis of CI assembly and IHC using an alternative, commercially-available CI (NDUFS3) antibody. (PMID:29142257)
• NDUFB8 is a relevant gene in childhood-onset mitochondrial disease. (PMID:29429571)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufb8	ENSDARG00000010113
mus_musculus	Ndufb8	ENSMUSG00000025204
rattus_norvegicus	Ndufb8	ENSRNOG00000014078
drosophila_melanogaster	ND-ASHI	FBGN0029888
caenorhabditis_elegans		WBGENE00013094

Protein

Protein identifiers

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial — O95169 (reviewed: O95169)

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

All UniProt accessions (2): E9PIZ8, O95169

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.

Disease relevance. Mitochondrial complex I deficiency, nuclear type 32 (MC1DN32) [MIM:618252] 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. MC1DN32 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 NDUFB8 subunit family.

Isoforms (3)

UniProt ID	Names	Canonical?
O95169-1	1	yes
O95169-2	2
O95169-3	3

RefSeq proteins (3): NP_001271296, NP_001271297, NP_004995* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008699	NDUFB8	Family
IPR016551	Ndufb8_metazoa	Family

Pfam: PF05821

UniProt features (13 total): sequence variant 4, sequence conflict 3, splice variant 3, transit peptide 1, chain 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-O95169-F1	88.64	0.81

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
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
R-HSA-9609507	Protein localization

MSigDB gene sets: 246 (showing top): MODULE_93, MULLIGHAN_NPM1_SIGNATURE_3_UP, TGCGCANK_UNKNOWN, PAL_PRMT5_TARGETS_UP, MODULE_77, GCANCTGNY_MYOD_Q6, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_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, ONKEN_UVEAL_MELANOMA_UP

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

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), respiratory chain complex I (GO:0045271), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Protein localization	1
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
mitochondrion	2
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
cellular respiration	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
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1
NADH dehydrogenase complex	1
respiratory chain complex	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3059 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDUFB8	SDHB	P21912	953
NDUFB8	NDUFB3	O43676	950
NDUFB8	UQCRC2	P22695	947
NDUFB8	NDUFB9	Q9Y6M9	946
NDUFB8	NDUFA7	O95182	904
NDUFB8	NDUFA2	O43678	899
NDUFB8	NDUFS8	O00217	893
NDUFB8	MT-CO1	P00395	892
NDUFB8	NDUFA9	Q16795	880
NDUFB8	NDUFA6	P56556	868
NDUFB8	NDUFB7	P17568	852
NDUFB8	NDUFS3	O75489	844
NDUFB8	ATP5F1A	P25705	840
NDUFB8	MRPL12	P52815	830
NDUFB8	NDUFS7	O75251	815

IntAct

124 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
VAPB	FAM83G	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
NDUFA9	NDUFS4	psi-mi:“MI:0914”(association)	0.640
NDUFS7	NDUFS8	psi-mi:“MI:0914”(association)	0.640
ASPH	STXBP3	psi-mi:“MI:0914”(association)	0.640
NDUFS5	NDUFS8	psi-mi:“MI:0914”(association)	0.530
NDUFA9	NDUFS8	psi-mi:“MI:0914”(association)	0.530
TIMMDC1	NDUFS8	psi-mi:“MI:0914”(association)	0.530
NDUFA8	NDUFS8	psi-mi:“MI:0914”(association)	0.530
ECSIT	NDUFS8	psi-mi:“MI:0914”(association)	0.530
FUT1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
GALNT6	NDUFS4	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
NDUFS5	NDUFS4	psi-mi:“MI:0914”(association)	0.530
NDUFC2	NDUFS4	psi-mi:“MI:0914”(association)	0.530

BioGRID (183): NDUFB8 (Affinity Capture-RNA), NDUFB8 (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), NDUFB8 (Co-fractionation), NDUFB8 (Co-fractionation), NDUFB8 (Co-fractionation), NDUFB8 (Co-fractionation), NDUFB8 (Co-fractionation), NDUFB8 (Co-fractionation), NDUFB8 (Co-fractionation)

ESM2 similar proteins: A3KP48, A8WGU8, O09111, O43674, O95169, O95178, P0C2B7, P0C2B9, P0CB69, P0CB70, P0CB85, P0CB86, P82649, P82927, P83565, Q02372, Q02380, Q0MQC7, Q0MQC9, Q0MQD6, Q0MQD7, Q0MQD8, Q0MQE6, Q0MQE7, Q0MQF5, Q0MQJ3, Q0MQJ4, Q0MQJ5, Q29259, Q2NKR7, Q4G0I0, Q4QQV3, Q4R4E0, Q5R4S3, Q5R504, Q5RFR4, Q6DQX6, Q6RUT7, Q8HXG5, Q96A26

Diamond homologs: O95169, P0CB85, P0CB86, Q02372, Q0MQE6, Q0MQE7, Q9D6J5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NDUFB8	“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 113 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	27	53.8×	4e-39
Respiratory electron transport	29	33.2×	2e-35
Aerobic respiration and respiratory electron transport	25	26.7×	1e-27
Complex IV assembly	6	16.5×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	20	71.0×	8e-31
proton motive force-driven mitochondrial ATP synthesis	22	57.4×	4e-31
aerobic respiration	22	54.0×	8e-31
mitochondrial respiratory chain complex I assembly	13	52.9×	1e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	54
Likely benign	34
Benign	9

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
548131	NM_005004.4(NDUFB8):c.227C>A (p.Pro76Gln)	Pathogenic
548132	NM_005004.4(NDUFB8):c.432C>G (p.Cys144Trp)	Pathogenic
548134	NM_005004.4(NDUFB8):c.184T>C (p.Tyr62His)	Pathogenic
1677231	NM_005004.4(NDUFB8):c.358del (p.Ser120fs)	Likely pathogenic

SpliceAI

882 predictions. Top by Δscore:

Variant	Effect	Δscore
10:100523834:T:TA	donor_gain	1.0000
10:100529364:AC:A	donor_gain	1.0000
10:100529365:CC:C	donor_gain	1.0000
10:100529365:CCCT:C	donor_gain	1.0000
10:100529392:T:TA	donor_gain	1.0000
10:100529432:T:TA	donor_gain	1.0000
10:100529730:C:CA	donor_gain	1.0000
10:100523830:AGCCT:A	donor_gain	0.9900
10:100523854:C:CT	donor_gain	0.9900
10:100523855:C:CT	donor_gain	0.9900
10:100526390:GATAC:G	donor_loss	0.9900
10:100526391:ATAC:A	donor_loss	0.9900
10:100526392:TAC:T	donor_loss	0.9900
10:100526393:ACTC:A	donor_loss	0.9900
10:100526394:C:CA	donor_loss	0.9900
10:100526395:TCACC:T	donor_loss	0.9900
10:100526396:C:CG	donor_loss	0.9900
10:100526398:CCA:C	donor_gain	0.9900
10:100526552:CAT:C	acceptor_gain	0.9900
10:100526554:TCT:T	acceptor_loss	0.9900
10:100526555:C:CA	acceptor_loss	0.9900
10:100526555:C:CC	acceptor_gain	0.9900
10:100526556:T:A	acceptor_loss	0.9900
10:100526556:T:G	acceptor_loss	0.9900
10:100526974:CCGGT:C	donor_gain	0.9900
10:100527072:TAC:T	acceptor_gain	0.9900
10:100527073:ACCT:A	acceptor_loss	0.9900
10:100527073:ACCTG:A	acceptor_loss	0.9900
10:100527074:CCTG:C	acceptor_loss	0.9900
10:100527074:CCTGA:C	acceptor_loss	0.9900

AlphaMissense

1227 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:100527013:A:G	W92R	0.985
10:100527013:A:T	W92R	0.985
10:100527011:C:A	W92C	0.984
10:100527011:C:G	W92C	0.984
10:100529437:G:T	A52D	0.983
10:100523921:C:A	K159N	0.979
10:100523921:C:G	K159N	0.979
10:100527061:G:A	P76S	0.968
10:100527060:G:T	P76Q	0.965
10:100529429:A:G	Y55H	0.962
10:100527067:C:G	D74H	0.960
10:100526520:C:G	R116P	0.959
10:100529428:T:G	Y55S	0.959
10:100526993:C:A	R98S	0.958
10:100526993:C:G	R98S	0.958
10:100527012:C:A	W92L	0.956
10:100529408:A:G	Y62H	0.956
10:100529441:C:G	A51P	0.956
10:100526987:G:C	N100K	0.955
10:100526987:G:T	N100K	0.955
10:100529440:G:T	A51D	0.954
10:100527069:C:A	G73V	0.953
10:100527065:G:C	D74E	0.952
10:100527065:G:T	D74E	0.952
10:100527061:G:T	P76T	0.951
10:100529429:A:C	Y55D	0.951
10:100526515:C:G	D118H	0.950
10:100526994:C:G	R98T	0.949
10:100529438:C:G	A52P	0.949
10:100527029:T:A	R86S	0.948

dbSNP variants (sampled 300 via entrez): RS1000314319 (10:100527149 T>C), RS1000645379 (10:100528807 T>C), RS1000941200 (10:100527602 A>G), RS1001527503 (10:100527615 A>C,G), RS1002011999 (10:100530692 T>C), RS1003540981 (10:100530693 C>T), RS1003789817 (10:100523753 A>C), RS1003795993 (10:100529115 C>T), RS1004571474 (10:100523591 T>C), RS1005328199 (10:100526308 GTA>G), RS1005364613 (10:100524271 G>A), RS1005571394 (10:100529384 T>A,C), RS1005790863 (10:100529622 C>T), RS1005903047 (10:100527976 C>G,T), RS1006122743 (10:100528297 T>C)

Disease associations

OMIM: gene MIM:602140 | disease phenotypes: MIM:618252

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex I deficiency, nuclear type 32	Strong	Autosomal recessive
Leigh syndrome with cardiomyopathy	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
Leigh syndrome	Moderate	AR
mitochondrial disease	Moderate	AR

Mondo (2): mitochondrial complex I deficiency, nuclear type 32 (MONDO:0032635), Leigh syndrome with cardiomyopathy (MONDO:0019083)

Orphanet (0):

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age
HP:0001942	Metabolic acidosis
HP:0002013	Vomiting
HP:0002059	Cerebral atrophy
HP:0002151	Increased circulating lactate concentration
HP:0002490	Increased CSF lactate
HP:0002878	Respiratory failure
HP:0002902	Hyponatremia
HP:0003202	Skeletal muscle atrophy
HP:0003593	Infantile onset
HP:0003819	Death in childhood
HP:0010479	Patent urachus
HP:0011923	Decreased activity of mitochondrial complex I

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001841_4	Palmitoleic acid (16:1n-7) levels	6.000000e-09
GCST010703_13	Brain morphology (MOSTest)	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363065 (PROTEIN COMPLEX), CHEMBL6066993 (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
6.13	Kd	738.2	nM	CHEMBL5653589
6.13	ED50	738.2	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	2148849: Binding affinity to human NDUFB8 incubated for 45 mins by Kinobead based pull down assay	kd	0.7382	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases reaction	2
Aerosols	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
cobaltiprotoporphyrin	increases expression, decreases reaction	1
deoxynivalenol	decreases expression	1
lead acetate	decreases expression, decreases reaction, increases abundance	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
plastochromanol 8	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
8-bromocyclic GMP	increases expression, decreases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
tris(chloroethyl)phosphate	decreases expression, increases abundance	1
tin protoporphyrin IX	increases reaction, decreases reaction, increases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one	decreases reaction, increases expression	1
chloropicrin	increases expression	1
S-nitro-N-acetylpenicillamine	decreases reaction, increases expression	1
K 7174	decreases expression	1
tricarbonylchloro(glycinato)ruthenium(II)	decreases reaction, increases expression	1
lipopolysaccharide, E coli O55-B5	increases expression, increases reaction, decreases reaction	1
2-ethylhexyl 2,3,4,5-tetrabromobenzoate	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	decreases reaction, increases expression, increases reaction	1
Telbivudine	decreases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Arsenic	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

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1P3	Abcam K-562 NDUFB8 KO	Cancer cell line	Female
CVCL_D2KN	Abcam Raji NDUFB8 KO	Cancer cell line	Male
CVCL_TA17	HAP1 NDUFB8 (-) 1	Cancer cell line	Male
CVCL_WQ05	Abcam Jurkat NDUFB8 KO	Cancer cell line	Male
CVCL_XQ88	HAP1 NDUFB8 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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