NDUFAF3

Summary

NDUFAF3 (NADH:ubiquinone oxidoreductase complex assembly factor 3, HGNC:29918) is a protein-coding gene on chromosome 3p21.31, encoding NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3 (Q9BU61). Essential factor for the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). It is a selective cancer dependency (DepMap: 28.0% of cell lines).

This gene encodes a mitochondrial complex I assembly protein that interacts with complex I subunits. Mutations in this gene cause mitochondrial complex I deficiency, a fatal neonatal disorder of the oxidative phosphorylation system. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 25915 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 15
• Clinical variants (ClinVar): 97 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 50
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 28.0% of screened cell lines
• MANE Select transcript: NM_199069

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29918
Approved symbol	NDUFAF3
Name	NADH:ubiquinone oxidoreductase complex assembly factor 3
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC10527, DKFZP564J0123, E3-3, 2P1
Ensembl gene	ENSG00000178057
Ensembl biotype	protein_coding
OMIM	612911
Entrez	25915

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

ENST00000326912, ENST00000326925, ENST00000395458, ENST00000451378, ENST00000480392, ENST00000496152, ENST00000886525

RefSeq mRNA: 4 — MANE Select: NM_199069 NM_199069, NM_199070, NM_199073, NM_199074

CCDS: CCDS2784, CCDS2785

Canonical transcript exons

ENST00000326925 — 5 exons

Exon	Start	End
ENSE00001309620	49022121	49022221
ENSE00001816598	49023056	49023495
ENSE00003560962	49022702	49022768
ENSE00003576462	49022876	49022976
ENSE00003648612	49022346	49022538

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 108.6771 / max 567.0138, expressed in 1825 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36610	90.9071	1823
36606	13.2091	1791
36607	1.7079	1056
36611	0.7854	514
36603	0.6048	227
36602	0.5244	156
36609	0.4067	175
36605	0.2392	68
36608	0.1940	68
36604	0.0985	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.57	gold quality
right testis	UBERON:0004534	99.53	gold quality
apex of heart	UBERON:0002098	98.57	gold quality
right atrium auricular region	UBERON:0006631	98.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.23	gold quality
right adrenal gland	UBERON:0001233	98.20	gold quality
left adrenal gland	UBERON:0001234	98.10	gold quality
adenohypophysis	UBERON:0002196	98.10	gold quality
left adrenal gland cortex	UBERON:0035825	98.10	gold quality
testis	UBERON:0000473	98.08	gold quality
right adrenal gland cortex	UBERON:0035827	97.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.86	gold quality
adrenal cortex	UBERON:0001235	97.83	gold quality
heart left ventricle	UBERON:0002084	97.70	gold quality
pituitary gland	UBERON:0000007	97.68	gold quality
adult organism	UBERON:0007023	97.67	gold quality
cardiac ventricle	UBERON:0002082	97.62	gold quality
spinal cord	UBERON:0002240	97.51	gold quality
cardiac atrium	UBERON:0002081	97.28	gold quality
nucleus accumbens	UBERON:0001882	97.18	gold quality
right lobe of thyroid gland	UBERON:0001119	97.06	gold quality
heart	UBERON:0000948	97.04	gold quality
adrenal gland	UBERON:0002369	97.00	gold quality
left lobe of thyroid gland	UBERON:0001120	96.98	gold quality
amygdala	UBERON:0001876	96.91	gold quality
right uterine tube	UBERON:0001302	96.90	gold quality
caudate nucleus	UBERON:0001873	96.87	gold quality
metanephros cortex	UBERON:0010533	96.86	gold quality
gastrocnemius	UBERON:0001388	96.84	gold quality
putamen	UBERON:0001874	96.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	30.23
E-GEOD-134144	yes	27.89
E-CURD-114	yes	11.13
E-HCAD-31	no	2.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

41 targeting NDUFAF3, 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-126-5P	100.00	72.71	3180
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 28.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• Describes a similar transcript in mouse. (PMID:12653254)
• Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease. (PMID:19463981)
• Describes a similar transcript in rat, and compares it to human and mouse transcripts. (PMID:9349717)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufaf3	ENSDARG00000112931
mus_musculus	Ndufaf3	ENSMUSG00000070283
rattus_norvegicus	Ndufaf3	ENSRNOG00000020068
drosophila_melanogaster	CG5569	FBGN0034919
caenorhabditis_elegans		WBGENE00011123

Protein

Protein identifiers

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3 — Q9BU61 (reviewed: Q9BU61)

All UniProt accessions (2): Q9BU61, A4FU71

UniProt curated annotations — full annotation on UniProt →

Function. Essential factor for the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).

Subunit / interactions. Interacts with NDUFAF4, NDUFS2 and NDUFS3.

Subcellular location. Nucleus. Mitochondrion inner membrane.

Disease relevance. Mitochondrial complex I deficiency, nuclear type 18 (MC1DN18) [MIM:618240] 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. MC1DN18 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 NDUFAF3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BU61-1	a	yes
Q9BU61-2	b

RefSeq proteins (4): NP_951032, NP_951033, NP_951047, NP_951056 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007523	NDUFAF3/AAMDC	Family
IPR034095	NDUF3	Family
IPR036748	MTH938-like_sf	Homologous_superfamily

Pfam: PF04430

UniProt features (5 total): sequence variant 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BU61-F1	79.02	0.55

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6799198	Complex I biogenesis
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-611105	Respiratory electron transport

MSigDB gene sets: 244 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, RNGTGGGC_UNKNOWN, TAATAAT_MIR126, GCANCTGNY_MYOD_Q6, CMYB_01, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, CAGCTG_AP4_Q5, MODULE_256, GATA1_01, MODULE_480, GOCC_MITOCHONDRIAL_ENVELOPE, MYOD_Q6, PU1_Q6, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (1): mitochondrial respiratory chain complex I assembly (GO:0032981)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Respiratory electron transport	1
Metabolism	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
NADH dehydrogenase complex assembly	1
mitochondrial respiratory chain complex assembly	1
binding	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1070 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDUFAF3	NDUFAF4	Q9P032	977
NDUFAF3	SERF1A	O75920	919
NDUFAF3	GPKOW	Q92917	909
NDUFAF3	C1S	P09871	880
NDUFAF3	NDUFS2	O75306	827
NDUFAF3	NDUFAF6	Q330K2	820
NDUFAF3	FOXRED1	Q96CU9	819
NDUFAF3	NDUFS3	O75489	818
NDUFAF3	TNFRSF11A	Q9Y6Q6	816
NDUFAF3	NDUFAF5	Q5TEU4	804
NDUFAF3	NDUFS7	O75251	802
NDUFAF3	NUBPL	Q8TB37	793
NDUFAF3	NDUFS8	O00217	793
NDUFAF3	NDUFAF2	Q8N183	785
NDUFAF3	NDUFAF1	Q9Y375	732

IntAct

107 interactions, top by confidence:

A	B	Type	Score
NDUFAF3	NDUFAF4	psi-mi:“MI:0915”(physical association)	0.890
NDUFAF1	NDUFS3	psi-mi:“MI:0914”(association)	0.790
NDUFAF4	NDUFS7	psi-mi:“MI:0914”(association)	0.790
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
NDUFAF3	SNRPA	psi-mi:“MI:0915”(physical association)	0.720
SNRPA	NDUFAF3	psi-mi:“MI:0915”(physical association)	0.720
NDUFS7	NDUFS8	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
	NDUFAF3	psi-mi:“MI:0915”(physical association)	0.560
NDUFAF3	RBCK1	psi-mi:“MI:0915”(physical association)	0.560
NDUFAF3		psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	NDUFAF3	psi-mi:“MI:0915”(physical association)	0.560
KRT27	NDUFAF3	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	NDUFAF3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (155): NDUFAF3 (Two-hybrid), NDUFAF3 (Two-hybrid), NDUFAF3 (Two-hybrid), NDUFAF4 (Two-hybrid), KRTAP10-3 (Two-hybrid), NDUFAF3 (Affinity Capture-MS), NDUFAF3 (Affinity Capture-MS), NDUFAF3 (Affinity Capture-MS), NDUFAF3 (Affinity Capture-MS), NDUFAF3 (Affinity Capture-MS), NDUFAF3 (Affinity Capture-MS), NDUFAF3 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF5 (Affinity Capture-MS), ECSIT (Affinity Capture-MS)

ESM2 similar proteins: A1L1F1, A4IHH4, A6H773, F1QWK4, O08776, P09925, P82923, Q08BI9, Q12851, Q148G5, Q15526, Q2HJI2, Q2KID9, Q2NL34, Q3T056, Q4FZX0, Q4KLZ1, Q4R8P0, Q4V7A9, Q5CZL1, Q5EA03, Q5EBA1, Q5REX5, Q5XGM5, Q5ZLJ4, Q61161, Q6DFN1, Q6DIS1, Q6PE15, Q7ZU92, Q800L1, Q80YD1, Q810A5, Q8BSF4, Q8R2L5, Q91WM2, Q921N7, Q924T2, Q96B77, Q99N87

Diamond homologs: A1L1F1, O08776, Q2HJI2, Q6DFN1, Q9BU61, Q9JKL4, Q9W1H9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 63 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	16	58.9×	6e-23
Respiratory electron transport	14	29.6×	1e-15
Aerobic respiration and respiratory electron transport	13	25.6×	1e-13
Mitochondrial protein degradation	5	12.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial respiratory chain complex I assembly	14	104.6×	4e-23
mitochondrial electron transport, NADH to ubiquinone	10	65.2×	6e-14
proton motive force-driven mitochondrial ATP synthesis	9	43.1×	8e-11
aerobic respiration	9	40.5×	1e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	46
Likely benign	28
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2674636	NM_199069.2(NDUFAF3):c.302G>A (p.Ser101Asn)	Pathogenic
423	NM_199069.2(NDUFAF3):c.365G>C (p.Arg122Pro)	Pathogenic
420990	NM_199069.2(NDUFAF3):c.447del (p.Cys150fs)	Likely pathogenic
638292	NM_199069.2(NDUFAF3):c.494C>T (p.Ala165Val)	Likely pathogenic

SpliceAI

834 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49022483:G:GT	donor_gain	1.0000
3:49022484:A:T	donor_gain	1.0000
3:49022525:T:TA	donor_gain	1.0000
3:49022526:GGTGC:G	donor_gain	1.0000
3:49022529:GC:G	donor_gain	1.0000
3:49022534:GGAAC:G	donor_gain	1.0000
3:49022535:GAAC:G	donor_gain	1.0000
3:49022535:GAACG:G	donor_gain	1.0000
3:49022536:A:T	donor_gain	1.0000
3:49022539:G:GG	donor_gain	1.0000
3:49022764:GA:G	donor_gain	1.0000
3:49022962:G:GT	donor_gain	1.0000
3:49022974:ACGGT:A	donor_loss	1.0000
3:49022976:GGTGA:G	donor_loss	1.0000
3:49022977:G:GG	donor_gain	1.0000
3:49022977:GTGAG:G	donor_loss	1.0000
3:49022978:T:A	donor_loss	1.0000
3:49022979:GAG:G	donor_loss	1.0000
3:49023054:A:AG	acceptor_gain	1.0000
3:49023055:G:GG	acceptor_gain	1.0000
3:49023055:GCCC:G	acceptor_gain	1.0000
3:49023055:GCCCA:G	acceptor_gain	1.0000
3:49023132:G:GT	donor_gain	1.0000
3:49020884:C:A	donor_gain	0.9900
3:49022536:AACG:A	donor_loss	0.9900
3:49022537:AC:A	donor_gain	0.9900
3:49022537:ACG:A	donor_loss	0.9900
3:49022538:CGTGA:C	donor_loss	0.9900
3:49022539:G:A	donor_loss	0.9900
3:49022540:TGA:T	donor_loss	0.9900

AlphaMissense

1164 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49022533:T:A	W89R	0.999
3:49022533:T:C	W89R	0.999
3:49022471:T:C	F68S	0.997
3:49022535:G:C	W89C	0.995
3:49022535:G:T	W89C	0.995
3:49022470:T:C	F68L	0.994
3:49022472:C:A	F68L	0.994
3:49022472:C:G	F68L	0.994
3:49023114:C:A	A166D	0.993
3:49022534:G:C	W89S	0.992
3:49023074:T:C	F153L	0.992
3:49023076:C:A	F153L	0.992
3:49023076:C:G	F153L	0.992
3:49022507:C:A	A80D	0.991
3:49022890:G:T	G118W	0.989
3:49022891:G:A	G118E	0.989
3:49023079:C:A	N154K	0.989
3:49023079:C:G	N154K	0.989
3:49023108:G:A	G164E	0.989
3:49022885:T:A	V116E	0.988
3:49023111:C:A	A165D	0.988
3:49023063:C:A	A149D	0.987
3:49022882:T:A	V115E	0.986
3:49023066:G:A	C150Y	0.985
3:49022888:T:A	V117E	0.984
3:49023065:T:C	C150R	0.984
3:49023067:T:G	C150W	0.984
3:49023117:T:C	L167P	0.984
3:49022447:T:A	I60N	0.983
3:49023117:T:A	L167H	0.983

dbSNP variants (sampled 300 via entrez): RS1000722810 (3:49021477 C>G), RS1001071680 (3:49021160 C>G,T), RS1001154759 (3:49020937 T>A,G), RS1001826933 (3:49023531 C>G,T), RS1002163618 (3:49020470 T>C), RS1002658274 (3:49019006 C>A,T), RS1002663376 (3:49018780 C>A), RS1002672401 (3:49018868 A>G), RS1002833397 (3:49019086 T>C), RS1003158995 (3:49018817 G>A), RS1004592788 (3:49021516 A>C,G), RS1004957287 (3:49020397 G>C), RS1005337641 (3:49020766 G>T), RS1005633120 (3:49023069 C>T), RS1005965266 (3:49021783 A>G,T)

Disease associations

OMIM: gene MIM:612911 | disease phenotypes: MIM:252010, MIM:618240

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex I deficiency, nuclear type 18	Strong	Autosomal recessive
mitochondrial complex I deficiency	Supportive	Autosomal recessive
Leigh syndrome with cardiomyopathy	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 (4): mitochondrial complex I deficiency (MONDO:0100133), mitochondrial complex I deficiency, nuclear type 1 (MONDO:0100224), mitochondrial complex I deficiency, nuclear type 18 (MONDO:0032623), Leigh syndrome with cardiomyopathy (MONDO:0019083)

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

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000072	Hydroureter
HP:0000114	Proximal tubulopathy
HP:0000126	Hydronephrosis
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
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:0001276	Hypertonia
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001522	Death in infancy
HP:0001639	Hypertrophic cardiomyopathy
HP:0001943	Hypoglycemia

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST007294_107	Body fat distribution (trunk fat ratio)	9.000000e-06
GCST007294_72	Body fat distribution (trunk fat ratio)	1.000000e-18
GCST007294_98	Body fat distribution (trunk fat ratio)	3.000000e-15
GCST007295_21	Body fat distribution (leg fat ratio)	8.000000e-06
GCST007295_45	Body fat distribution (leg fat ratio)	1.000000e-10
GCST007295_80	Body fat distribution (leg fat ratio)	1.000000e-14
GCST008357_20	Mood instability	4.000000e-11
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0008475	mood instability measurement
EFO:0004346	neuroimaging measurement

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

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Valproic Acid	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium bichromate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Diazinon	increases methylation	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Fluorouracil	decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	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)