NDUFAF1

Summary

NDUFAF1 (NADH:ubiquinone oxidoreductase complex assembly factor 1, HGNC:18828) is a protein-coding gene on chromosome 15q15.1, encoding Complex I intermediate-associated protein 30, mitochondrial (Q9Y375). As part of the MCIA complex, involved in the assembly of the mitochondrial complex I. It is a selective cancer dependency (DepMap: 36.6% of cell lines).

This gene encodes a complex I assembly factor protein. Complex I (NADH-ubiquinone oxidoreductase) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. The encoded protein is required for assembly of complex I, and mutations in this gene are a cause of mitochondrial complex I deficiency. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 19.

Source: NCBI Gene 51103 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial complex I deficiency, nuclear type 11 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 206 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 51
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 36.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_016013

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18828
Approved symbol	NDUFAF1
Name	NADH:ubiquinone oxidoreductase complex assembly factor 1
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	CIA30, CGI-65
Ensembl gene	ENSG00000137806
Ensembl biotype	protein_coding
OMIM	606934
Entrez	51103

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 24 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000260361, ENST00000558719, ENST00000559127, ENST00000560978, ENST00000676533, ENST00000676906, ENST00000677477, ENST00000678029, ENST00000678745, ENST00000679094, ENST00000679240, ENST00000853302, ENST00000853303, ENST00000853304, ENST00000853305, ENST00000853306, ENST00000853307, ENST00000853308, ENST00000853309, ENST00000853310, ENST00000853311, ENST00000853312, ENST00000853313, ENST00000853314, ENST00000853315, ENST00000928271, ENST00000928272, ENST00000928273, ENST00000949842

RefSeq mRNA: 1 — MANE Select: NM_016013 NM_016013

CCDS: CCDS10075

Canonical transcript exons

ENST00000260361 — 5 exons

Exon	Start	End
ENSE00000931001	41387353	41387593
ENSE00000931003	41394859	41395044
ENSE00002542527	41402144	41402496
ENSE00003559668	41388448	41388522
ENSE00003797164	41396487	41397140

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 94.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9499 / max 129.1825, expressed in 1736 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149524	5.9499	1736

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	94.39	gold quality
gastrocnemius	UBERON:0001388	93.72	gold quality
right adrenal gland	UBERON:0001233	93.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.55	gold quality
muscle of leg	UBERON:0001383	93.40	gold quality
right adrenal gland cortex	UBERON:0035827	93.33	gold quality
heart right ventricle	UBERON:0002080	92.91	gold quality
left adrenal gland	UBERON:0001234	92.68	gold quality
adrenal tissue	UBERON:0018303	92.55	gold quality
muscle organ	UBERON:0001630	92.50	gold quality
skeletal muscle organ	UBERON:0014892	92.50	gold quality
heart left ventricle	UBERON:0002084	92.18	gold quality
left adrenal gland cortex	UBERON:0035825	92.14	gold quality
cardiac ventricle	UBERON:0002082	92.04	gold quality
sperm	CL:0000019	92.03	gold quality
deltoid	UBERON:0001476	91.80	silver quality
adrenal cortex	UBERON:0001235	91.68	gold quality
adrenal gland	UBERON:0002369	91.52	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.29	gold quality
biceps brachii	UBERON:0001507	90.84	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.59	gold quality
right atrium auricular region	UBERON:0006631	90.52	gold quality
esophagus squamous epithelium	UBERON:0006920	90.33	gold quality
heart	UBERON:0000948	90.27	gold quality
vastus lateralis	UBERON:0001379	90.25	gold quality
prefrontal cortex	UBERON:0000451	90.23	gold quality
skeletal muscle tissue	UBERON:0001134	90.21	gold quality
gluteal muscle	UBERON:0002000	90.10	gold quality
quadriceps femoris	UBERON:0001377	90.05	gold quality
right lobe of liver	UBERON:0001114	89.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.11

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 36.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• NDUFAF1 is an important protein for the assembly/stability of complex I (NADH:ubiquinone oxidoreductase). (PMID:16218961)
• Study shows a mitochondrial function for Ecsit in the assembly of mitochondrial complex I, an N-terminal targeting signal directs Ecsit to mitochondria, where it interacts with assembly chaperone NDUFAF1. (PMID:17344420)
• the involvement of NDUFAF1 in the assembly process could be indirect rather than direct via the binding to assembly intermediates (PMID:17383918)
• CIA30 is a crucial component in the early assembly of complex I and mutations in its gene can cause mitochondrial disease (PMID:17557076)
• a case of leukodystrophy associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFAF1 gene. (PMID:24963768)
• oncogenic K-Ras is able to induce significant alterations in mitochondrial protein expression, and identified NDUFAF1 as an important molecule whose low expression contributes to mitochondrial dysfunction induced by K-Ras. (PMID:25714130)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufaf1	ENSDARG00000025549
mus_musculus	Ndufaf1	ENSMUSG00000027305
rattus_norvegicus	Ndufaf1	ENSRNOG00000005006
drosophila_melanogaster	CIA30	FBGN0039689
caenorhabditis_elegans		WBGENE00008225

Protein

Protein identifiers

Complex I intermediate-associated protein 30, mitochondrial — Q9Y375 (reviewed: Q9Y375)

Alternative names: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 1

All UniProt accessions (6): A0A7I2V4I7, A0A7I2YQA4, Q9Y375, H0YL22, H0YNB7, H0YNN4

UniProt curated annotations — full annotation on UniProt →

Function. As part of the MCIA complex, involved in the assembly of the mitochondrial complex I.

Subunit / interactions. Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186. Interacts with ECSIT. Interacts with ACAD9. At early stages of complex I assembly, it is found in intermediate subcomplexes that contain different subunits including NDUFB6, NDUFA6, NDUFA9, NDUFS3, NDUFS7, ND1, ND2 and ND3. Interacts with TMEM70 and TMEM242.

Subcellular location. Mitochondrion. Mitochondrion matrix.

Tissue specificity. Ubiquitous.

Disease relevance. Mitochondrial complex I deficiency, nuclear type 11 (MC1DN11) [MIM:618234] 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. MC1DN11 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 CIA30 family.

RefSeq proteins (1): NP_057097* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR013857	NADH-UbQ_OxRdtase-assoc_prot30	Domain
IPR039131	NDUFAF1	Family

Pfam: PF08547

UniProt features (16 total): sequence variant 9, sequence conflict 2, transit peptide 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y375-F1	73.37	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 318

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6799198	Complex I biogenesis

MSigDB gene sets: 285 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, MORF_HDAC2, GOBP_CHAPERONE_MEDIATED_PROTEIN_COMPLEX_ASSEMBLY, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_OXIDATIVE_PHOSPHORYLATION, BROWNE_HCMV_INFECTION_14HR_DN, GOBP_ELECTRON_TRANSPORT_CHAIN, PETRETTO_HEART_MASS_QTL_CIS_DN, GOCC_MITOCHONDRIAL_ENVELOPE, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, WONG_MITOCHONDRIA_GENE_MODULE, SASAKI_ADULT_T_CELL_LEUKEMIA, GOBP_CELLULAR_RESPIRATION, GOCC_MITOCHONDRIAL_MATRIX

GO Biological Process (4): mitochondrial electron transport, NADH to ubiquinone (GO:0006120), mitochondrial respiratory chain complex I assembly (GO:0032981), chaperone-mediated protein complex assembly (GO:0051131), protein-containing complex assembly (GO:0065003)

GO Molecular Function (2): obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
NADH dehydrogenase complex assembly	1
mitochondrial respiratory chain complex assembly	1
protein-containing complex assembly	1
cellular component assembly	1
protein-containing complex organization	1
binding	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDUFAF1	ECSIT	Q9BQ95	998
NDUFAF1	ACAD9	Q9H845	988
NDUFAF1	TMEM126B	Q8IUX1	977
NDUFAF1	NDUFAF6	Q330K2	913
NDUFAF1	FOXRED1	Q96CU9	856
NDUFAF1	TMEM186	Q96B77	822
NDUFAF1	NDUFAF4	Q9P032	822
NDUFAF1	TIMMDC1	Q9NPL8	815
NDUFAF1	NDUFAF5	Q5TEU4	795
NDUFAF1	NDUFS7	O75251	770
NDUFAF1	NDUFAF2	Q8N183	754
NDUFAF1	NUBPL	Q8TB37	745
NDUFAF1	NDUFA12	Q9UI09	738
NDUFAF1	NDUFAF3	Q9BU61	732
NDUFAF1	MT-ND1	P03886	723

IntAct

184 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
NDUFAF1	NDUFS3	psi-mi:“MI:0914”(association)	0.790
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
PPP2R2D	YEATS4	psi-mi:“MI:0914”(association)	0.730
TIMMDC1	ECSIT	psi-mi:“MI:0914”(association)	0.730
PPP2R1A	PPFIA3	psi-mi:“MI:0914”(association)	0.670
ASPH	STXBP3	psi-mi:“MI:0914”(association)	0.640
NDUFA13	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFB5	NDUFB3	psi-mi:“MI:0914”(association)	0.640
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFS7	NDUFS8	psi-mi:“MI:0914”(association)	0.640
RETREG3	PLSCR1	psi-mi:“MI:0914”(association)	0.640
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.640
CERS2	ATP5F1B	psi-mi:“MI:0914”(association)	0.640

BioGRID (222): NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Two-hybrid), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS)

ESM2 similar proteins: A2ARP1, A7Z050, F4J8C6, G5EF51, O08600, O43314, O75460, P08466, P0C644, P38447, P81203, P81204, Q0IH72, Q0MQ82, Q0MQ83, Q0MQ84, Q10480, Q14249, Q14703, Q2TBM9, Q3U213, Q502K1, Q5EAB6, Q5RCB9, Q5RDF1, Q5REW0, Q5SNQ7, Q5U2Z5, Q5XHF8, Q5XIN7, Q6GQ76, Q6PFW1, Q6ZQB6, Q7ZU90, Q803R5, Q8C163, Q8VEG4, Q8WZA1, Q91X88, Q95NM6

Diamond homologs: Q0MQ82, Q0MQ83, Q0MQ84, Q18726, Q61FQ3, Q9CWX2, Q9VAI1, Q9Y375

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 170 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
Lysosphingolipid and LPA receptors	5	32.5×	2e-05
Complex I biogenesis	21	29.7×	2e-23
Respiratory electron transport	20	16.3×	9e-17
Aerobic respiration and respiratory electron transport	20	15.1×	3e-16
Class A/1 (Rhodopsin-like receptors)	11	7.0×	3e-05
Mitochondrial protein degradation	7	6.8×	4e-03
GPCR ligand binding	12	6.6×	2e-05
Signaling by GPCR	14	4.8×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial respiratory chain complex I assembly	14	36.6×	6e-16
mitochondrial electron transport, NADH to ubiquinone	12	27.4×	3e-12
proton motive force-driven mitochondrial ATP synthesis	15	25.2×	9e-15
aerobic respiration	14	22.1×	5e-13
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	8	11.2×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	132
Likely benign	36
Benign	18

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
214732	NM_016013.4(NDUFAF1):c.2T>C (p.Met1Thr)	Pathogenic
30622	NM_016013.4(NDUFAF1):c.619A>C (p.Thr207Pro)	Pathogenic
419281	NM_016013.4(NDUFAF1):c.532del (p.Thr178fs)	Pathogenic
214733	NM_016013.4(NDUFAF1):c.650G>A (p.Arg217Gln)	Likely pathogenic

SpliceAI

883 predictions. Top by Δscore:

Variant	Effect	Δscore
15:41388442:TGTTA:T	donor_loss	1.0000
15:41388443:GTTAC:G	donor_loss	1.0000
15:41388444:TTA:T	donor_loss	1.0000
15:41388445:TACCT:T	donor_loss	1.0000
15:41388446:ACCT:A	donor_loss	1.0000
15:41388447:CCT:C	donor_loss	1.0000
15:41387589:GAGAT:G	acceptor_gain	0.9900
15:41387591:GAT:G	acceptor_gain	0.9900
15:41387594:C:CC	acceptor_gain	0.9900
15:41388494:T:TC	acceptor_gain	0.9900
15:41388518:GGAAT:G	acceptor_gain	0.9900
15:41388522:TCTG:T	acceptor_loss	0.9900
15:41388523:C:CC	acceptor_gain	0.9900
15:41388523:C:T	acceptor_loss	0.9900
15:41394853:TGTTA:T	donor_loss	0.9900
15:41394854:GTTA:G	donor_loss	0.9900
15:41394855:TTA:T	donor_loss	0.9900
15:41394856:TA:T	donor_loss	0.9900
15:41394857:A:AG	donor_loss	0.9900
15:41394858:C:G	donor_loss	0.9900
15:41394860:TTG:T	donor_gain	0.9900
15:41394861:TG:T	donor_gain	0.9900
15:41394866:T:TA	donor_gain	0.9900
15:41395043:CC:C	acceptor_gain	0.9900
15:41395044:CC:C	acceptor_gain	0.9900
15:41396485:AC:A	donor_gain	0.9900
15:41396486:CC:C	donor_gain	0.9900
15:41396614:T:TA	donor_gain	0.9900
15:41402322:ACGG:A	donor_gain	0.9900
15:41402323:CGGC:C	donor_gain	0.9900

AlphaMissense

2180 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:41396654:A:G	W136R	0.999
15:41396654:A:T	W136R	0.999
15:41394963:A:G	W219R	0.997
15:41394963:A:T	W219R	0.997
15:41394980:C:G	R213P	0.997
15:41394968:C:G	R217P	0.996
15:41394989:A:G	L210P	0.996
15:41387541:A:G	L296P	0.995
15:41394871:C:A	W249C	0.995
15:41394871:C:G	W249C	0.995
15:41387577:A:G	F284S	0.994
15:41394873:A:G	W249R	0.994
15:41394873:A:T	W249R	0.994
15:41394986:C:G	R211P	0.994
15:41396566:C:T	G165E	0.994
15:41395014:A:G	W202R	0.993
15:41395014:A:T	W202R	0.993
15:41396511:A:C	C183W	0.993
15:41396616:A:C	S148R	0.993
15:41396616:A:T	S148R	0.993
15:41396618:T:G	S148R	0.993
15:41387546:G:C	F294L	0.992
15:41387546:G:T	F294L	0.992
15:41387548:A:G	F294L	0.992
15:41394978:C:A	G214W	0.992
15:41396642:A:G	S140P	0.992
15:41388506:A:G	F259S	0.991
15:41394977:C:T	G214E	0.991
15:41394981:G:T	R213S	0.991
15:41396680:A:G	F127S	0.991

dbSNP variants (sampled 300 via entrez): RS1000031689 (15:41387733 C>A,T), RS1000326801 (15:41394343 A>G), RS1000435575 (15:41396252 G>C), RS1000891905 (15:41390108 C>CA), RS1001037973 (15:41389227 C>G,T), RS1001079811 (15:41396678 G>A,C,T), RS1001206892 (15:41393503 G>A), RS1001275234 (15:41399045 G>A), RS1001403742 (15:41404620 T>A), RS1001497860 (15:41403184 C>G,T), RS1001519960 (15:41404320 G>A), RS1001550089 (15:41402743 T>C), RS1001827704 (15:41397240 T>A), RS1001829920 (15:41404311 C>T), RS1001885463 (15:41404128 T>C,G)

Disease associations

OMIM: gene MIM:606934 | disease phenotypes: MIM:618234, MIM:252010

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex I deficiency, nuclear type 11	Strong	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	Moderate	AR

Mondo (3): mitochondrial complex I deficiency, nuclear type 11 (MONDO:0032617), mitochondrial complex I deficiency, nuclear type 1 (MONDO:0100224), mitochondrial complex I deficiency (MONDO:0100133)

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

HPO phenotypes

51 total (30 of 51 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000114	Proximal tubulopathy
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000543	Optic disc pallor
HP:0000580	Pigmentary retinopathy
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000817	Reduced eye contact
HP:0000819	Diabetes mellitus
HP:0000939	Osteoporosis
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:0001403	Macrovesicular hepatic steatosis
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001635	Congestive heart failure
HP:0001639	Hypertrophic cardiomyopathy
HP:0001716	Wolff-Parkinson-White syndrome
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia
HP:0002013	Vomiting
HP:0002093	Respiratory insufficiency

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001728_13	Ulcerative colitis	2.000000e-08
GCST004133_26	Ulcerative colitis	3.000000e-07
GCST004600_23	Eosinophil percentage of white cells	2.000000e-10
GCST007563_20	Allergic disease (asthma, hay fever or eczema)	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes

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

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
GSK-J4	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
MT19c compound	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Fluorouracil	increases expression	1
Hydrogen Peroxide	affects expression	1
Methotrexate	increases expression	1
Nickel	decreases expression	1
Oxygen	decreases expression	1
Pesticides	affects methylation	1
Tetrachlorodibenzodioxin	decreases expression	1
Tunicamycin	decreases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	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)