COXFA4L2

Summary

COXFA4L2 (cytochrome c oxidase hypoxia associated subunit FA4L2, HGNC:29836) is a protein-coding gene on chromosome 12q13.3, encoding Cytochrome c oxidase hypoxia associated subunit FA4L2 (Q9NRX3). Mitochondrial protein that plays a regulatory role in cellular metabolism, particularly under hypoxic conditions.

Located in mitochondrion.

Source: NCBI Gene 56901 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 19 total
• Druggable target: yes
• MANE Select transcript: NM_001394961

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29836
Approved symbol	COXFA4L2
Name	cytochrome c oxidase hypoxia associated subunit FA4L2
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	NUOMS, FLJ26118, MISTRH
Ensembl gene	ENSG00000185633
Ensembl biotype	protein_coding
Entrez	56901

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000393825, ENST00000554503, ENST00000554688, ENST00000555173, ENST00000556234, ENST00000556732, ENST00000557276, ENST00000909958

RefSeq mRNA: 3 — MANE Select: NM_001394961 NM_001394960, NM_001394961, NM_020142

CCDS: CCDS8935

Canonical transcript exons

ENST00000554503 — 4 exons

Exon	Start	End
ENSE00001304056	57236593	57236681
ENSE00002476705	57237029	57237104
ENSE00002536194	57234903	57235619
ENSE00003637582	57235749	57235809

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 99.30.

FANTOM5 (CAGE): breadth broad, TPM avg 13.0596 / max 1816.9861, expressed in 828 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131651	12.4685	634
131654	0.4085	257
131653	0.1826	89

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.30	gold quality
right coronary artery	UBERON:0001625	98.90	gold quality
apex of heart	UBERON:0002098	98.85	gold quality
skin of abdomen	UBERON:0001416	97.63	gold quality
popliteal artery	UBERON:0002250	97.46	gold quality
tibial artery	UBERON:0007610	97.45	gold quality
left coronary artery	UBERON:0001626	97.38	gold quality
skin of leg	UBERON:0001511	96.94	gold quality
coronary artery	UBERON:0001621	96.78	gold quality
esophagus mucosa	UBERON:0002469	96.64	gold quality
aorta	UBERON:0000947	96.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.36	gold quality
ascending aorta	UBERON:0001496	96.03	gold quality
cerebellar hemisphere	UBERON:0002245	95.80	gold quality
thoracic aorta	UBERON:0001515	95.75	gold quality
cerebellar cortex	UBERON:0002129	95.44	gold quality
right atrium auricular region	UBERON:0006631	95.30	gold quality
heart left ventricle	UBERON:0002084	95.09	gold quality
zone of skin	UBERON:0000014	94.87	gold quality
omental fat pad	UBERON:0010414	94.84	gold quality
cardiac ventricle	UBERON:0002082	94.78	gold quality
peritoneum	UBERON:0002358	94.77	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.03	gold quality
descending thoracic aorta	UBERON:0002345	93.95	gold quality
esophagus	UBERON:0001043	93.71	gold quality
cartilage tissue	UBERON:0002418	93.34	gold quality
heart	UBERON:0000948	93.24	gold quality
right frontal lobe	UBERON:0002810	93.16	gold quality
cardiac atrium	UBERON:0002081	92.98	gold quality
right lobe of thyroid gland	UBERON:0001119	92.93	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	3532.49
E-MTAB-11121	yes	2476.32
E-CURD-126	yes	2405.86
E-HCAD-11	yes	1542.27
E-MTAB-6308	yes	1439.48
E-GEOD-124263	yes	1329.71
E-MTAB-8381	yes	1047.55
E-HCAD-24	yes	926.72
E-HCAD-10	yes	59.11
E-MTAB-10287	yes	50.39
E-MTAB-6701	yes	44.42
E-GEOD-135922	yes	29.56
E-MTAB-8410	yes	25.85
E-GEOD-134144	yes	12.56
E-CURD-46	yes	12.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting COXFA4L2, 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-3646	100.00	73.56	5283
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-5580-5P	99.38	66.96	1139

Literature-anchored findings (GeneRIF, showing 13)

• NDUFA4L2 knockdown has a profound antiproliferative effect, alters metabolic pathways, and causes major stress in cultured clear cell renal cell carcinoma cells. (PMID:26783287)
• This study has provided the first clinical relevance of NDUFA4L2 in human cancer, and since NDUFA4L2 was HIF1-regulated in Hepatocellular carcinoma cells, suggested that Hepatocellular carcinoma patients with NDUFA4L2 overexpression may be suitable candidates for HIF inhibitor treatment. (PMID:26819450)
• NDUFA4L2 expression levels were correlated with some clinical features of clear cell renal cell carcinoma (ccRCC). Multivariate analysis showed NDUFA4L2 expression was an independent prognostic factor for ccRCC patients. (PMID:27453328)
• hypoxia promotes the viability of cardiac stem cells in serum-free medium by HIF-1alpha/NDUFA4L2 signaling pathway. (PMID:29953852)
• This study identified NDUFA4L2 as the most highly expressed gene in renal cancer cells and evaluated its role in sustaining angiogenesis, chemoresistance, and mitochondrial dysfunction. (PMID:30538212)
• Study showed that mitochondrial NDUFA4L2 was overexpressed in non-small cell lung cancer (NSCLC) tumor tissues. NDUFA4L2 was also overexpressed in NSCLC cell lines cultured in hypoxic conditions. Its expression is regulated by HIF1A. (PMID:30710412)
• Evaluating the clinical significance of SHMT2 and its co-expressed gene in human kidney cancer. (PMID:33066813)
• NDUFA4L2 in smooth muscle promotes vascular remodeling in hypoxic pulmonary arterial hypertension. (PMID:33340241)
• NDUFA4L2 promotes glioblastoma progression, is associated with poor survival, and can be effectively targeted by apatinib. (PMID:33828084)
• Unique expression of the atypical mitochondrial subunit NDUFA4L2 in cerebral pericytes fine tunes HIF activity in response to hypoxia. (PMID:35929074)
• Transcriptional regulation of NDUFA4L2 by NFIB induces sorafenib resistance by decreasing reactive oxygen species in hepatocellular carcinoma. (PMID:36369883)
• NDUFA4L2 reduces mitochondrial respiration resulting in defective lysosomal trafficking in clear cell renal cell carcinoma. (PMID:36722045)
• Pancancer analysis of NDUFA4L2 with focused role in tumor progression and metastasis of colon adenocarcinoma. (PMID:39402288)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufa4l2b	ENSDARG00000087907
danio_rerio	ndufa4l2a	ENSDARG00000103114
mus_musculus	Ndufa4l2	ENSMUSG00000040280
rattus_norvegicus	Ndufa4l2	ENSRNOG00000031851

Paralogs (2): C15orf48 (ENSG00000166920), NDUFA4 (ENSG00000189043)

Protein

Protein identifiers

Cytochrome c oxidase hypoxia associated subunit FA4L2 — Q9NRX3 (reviewed: Q9NRX3)

Alternative names: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2, NADH-ubiquinone oxidoreductase MLRQ subunit homolog

All UniProt accessions (2): G3V560, Q9NRX3

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial protein that plays a regulatory role in cellular metabolism, particularly under hypoxic conditions. Downregulates mitochondrial respiratory chain complex I activity under hypoxia, reduces oxygen consumption and ROS and helps cells adapt by switching to glycolysis.

Subcellular location. Mitochondrion inner membrane.

Induction. Upon hypoxia, expression is induced by HIF1A.

Similarity. Belongs to the complex IV COXFA4 subunit family.

RefSeq proteins (3): NP_001381889, NP_001381890, NP_064527 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010530	B12D	Family

Pfam: PF06522

UniProt features (2 total): chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRX3-F1	84.56	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 187 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, BENPORATH_ES_WITH_H3K27ME3, MYOGENIN_Q6, LFA1_Q6, GCANCTGNY_MYOD_Q6, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, AP4_Q6, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, CHX10_01, CAGCTG_AP4_Q5, SP1_Q2_01, CEBPB_01, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_REGULATION_OF_OXIDATIVE_PHOSPHORYLATION

GO Biological Process (3): response to hypoxia (GO:0001666), cellular response to hypoxia (GO:0071456), negative regulation of mitochondrial electron transport, NADH to ubiquinone (GO:1902957)

GO Molecular Function (0):

GO Cellular Component (3): mitochondrion (GO:0005739), respiratory chain complex IV (GO:0045277), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to stress	1
response to decreased oxygen levels	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
mitochondrial electron transport, NADH to ubiquinone	1
regulation of mitochondrial electron transport, NADH to ubiquinone	1
negative regulation of mitochondrial ATP synthesis coupled electron transport	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cytochrome complex	1
respiratory chain complex	1
transmembrane transporter complex	1
oxidoreductase complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COXFA4L2	COX4I2	Q96KJ9	574
COXFA4L2	FXYD4	P59646	553
COXFA4L2	HIGD1A	Q9Y241	547
COXFA4L2	SPINK14	Q6IE38	532
COXFA4L2	SPINK9	Q5DT21	527
COXFA4L2	OR1E1	P30953	494
COXFA4L2	SPINK7	P58062	471
COXFA4L2	PILRA	Q9UKJ1	444
COXFA4L2	SPATA18	Q8TC71	437
COXFA4L2	COX4I1	P13073	423
COXFA4L2	UNC45B	Q8IWX7	421
COXFA4L2	CA9	Q16790	418
COXFA4L2	FASTKD2	Q9NYY8	410
COXFA4L2	NDUFS8	O00217	403
COXFA4L2	EGFR	P00533	398

IntAct

21 interactions, top by confidence:

A	B	Type	Score
NDUFA4L2	POTEI	psi-mi:“MI:0914”(association)	0.530
NDUFA4L2	NUFIP2	psi-mi:“MI:0915”(physical association)	0.370
ERBB2	DNM1L	psi-mi:“MI:0914”(association)	0.350
MYC	AP3B1	psi-mi:“MI:0914”(association)	0.350
STAT3	IDH3B	psi-mi:“MI:0914”(association)	0.350
NDUFA4L2	SLC35F6	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	ERG28	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	DYNLL1	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	KAT5	psi-mi:“MI:0915”(physical association)	0.000
KCNA4	NDUFA4L2	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	SUMO2	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	LUC7L2	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	UBR1	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	ANXA9	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	PRKN	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	QTRT1	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	C6orf62	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	COMMD8	psi-mi:“MI:0915”(physical association)	0.000
NDUFA4L2	EIF3C	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): POTEI (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), ACTC1 (Affinity Capture-MS), NDUFA4L2 (Negative Genetic), NDUFA4L2 (Positive Genetic), NTRK1 (Positive Genetic), NDUFA4L2 (Positive Genetic), PDK2 (Positive Genetic), NDUFA4L2 (Positive Genetic), NDUFA4L2 (Positive Genetic), ANXA9 (Two-hybrid), PARK2 (Two-hybrid), QTRT1 (Two-hybrid), C14orf1 (Two-hybrid)

ESM2 similar proteins: A2VDV9, A5PJ82, A8MTT3, D3Z9R8, D3ZAF6, D4ACP2, E7EXZ6, G1QDE8, G1S9B8, O00483, P0DO44, P0DO45, P14790, P46269, P46270, P56134, P56135, P56378, P56379, P56392, P80497, Q01321, Q0MQ97, Q0MQ98, Q0MQ99, Q28851, Q28GF4, Q3SZ44, Q3YAJ5, Q4FZG9, Q4R542, Q5R6T5, Q5RCY6, Q5REX0, Q62425, Q6PBH5, Q78RX3, Q7YRK7, Q8BTC1, Q8BTE5

Diamond homologs: O00483, Q01321, Q0MQ97, Q0MQ98, Q0MQ99, Q3SZ44, Q3YAJ5, Q4FZG9, Q4R542, Q5RK28, Q62425, Q6PBH5, Q810Q5, Q9NRX3, Q9C002

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

779 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57235744:GGTA:G	donor_loss	1.0000
12:57235745:GTA:G	donor_loss	1.0000
12:57235746:TA:T	donor_loss	1.0000
12:57235747:A:AG	donor_loss	1.0000
12:57235748:CCT:C	donor_loss	1.0000
12:57235805:CCCAG:C	acceptor_gain	1.0000
12:57235806:CCAG:C	acceptor_gain	1.0000
12:57235806:CCAGC:C	acceptor_gain	1.0000
12:57235807:CAG:C	acceptor_gain	1.0000
12:57235807:CAGC:C	acceptor_gain	1.0000
12:57235808:AG:A	acceptor_gain	1.0000
12:57235809:GC:G	acceptor_loss	1.0000
12:57235810:C:CC	acceptor_gain	1.0000
12:57236677:ATGAT:A	acceptor_gain	1.0000
12:57236678:TGAT:T	acceptor_gain	1.0000
12:57236679:GAT:G	acceptor_gain	1.0000
12:57236679:GATC:G	acceptor_loss	1.0000
12:57236680:AT:A	acceptor_gain	1.0000
12:57236680:ATCT:A	acceptor_loss	1.0000
12:57236681:TCTG:T	acceptor_loss	1.0000
12:57236682:C:CC	acceptor_gain	1.0000
12:57236682:C:CG	acceptor_loss	1.0000
12:57236683:T:G	acceptor_loss	1.0000
12:57235620:C:CC	acceptor_gain	0.9900
12:57235812:G:C	acceptor_gain	0.9900
12:57235818:C:CT	acceptor_gain	0.9900
12:57235819:A:T	acceptor_gain	0.9900
12:57236588:TTTA:T	donor_loss	0.9900
12:57236589:TTACC:T	donor_loss	0.9900
12:57236590:TAC:T	donor_loss	0.9900

AlphaMissense

567 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57235566:G:C	F87L	0.994
12:57235566:G:T	F87L	0.994
12:57235568:A:G	F87L	0.994
12:57235779:C:A	W59C	0.990
12:57235779:C:G	W59C	0.990
12:57235749:C:A	K69N	0.989
12:57235749:C:G	K69N	0.989
12:57235781:A:G	W59R	0.989
12:57235781:A:T	W59R	0.989
12:57236640:G:C	S33R	0.985
12:57236640:G:T	S33R	0.985
12:57236642:T:G	S33R	0.985
12:57235806:C:A	W50C	0.980
12:57235806:C:G	W50C	0.980
12:57235808:A:G	W50R	0.978
12:57235808:A:T	W50R	0.978
12:57236645:C:G	G32R	0.976
12:57235567:A:C	F87C	0.975
12:57235780:C:A	W59L	0.975
12:57235567:A:G	F87S	0.973
12:57235618:A:G	F70S	0.970
12:57236650:C:T	G30D	0.970
12:57235751:T:C	K69E	0.969
12:57236604:G:C	S45R	0.969
12:57236604:G:T	S45R	0.969
12:57236606:T:G	S45R	0.969
12:57236614:G:T	A42D	0.968
12:57236651:C:G	G30R	0.968
12:57236638:G:T	A34D	0.965
12:57235750:T:A	K69M	0.962

dbSNP variants (sampled 300 via entrez): RS1000009426 (12:57236389 G>A,C,T), RS1000374107 (12:57239056 C>G,T), RS1000613648 (12:57235378 C>A,G,T), RS1000734887 (12:57240202 C>T), RS1000850852 (12:57239309 T>A,C), RS1000943446 (12:57235225 G>A), RS1001067803 (12:57239158 A>G), RS1001170585 (12:57238212 A>C), RS1001550836 (12:57238530 C>G), RS1001956245 (12:57240126 C>G,T), RS1001960181 (12:57234679 G>A), RS1002024082 (12:57238944 G>A), RS1002344510 (12:57234947 G>A), RS1002985753 (12:57239683 G>T), RS1003278909 (12:57240953 CACTA>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002539_15	Schizophrenia	2.000000e-12
GCST004521_233	Autism spectrum disorder or schizophrenia	4.000000e-10
GCST006803_97	Schizophrenia	3.000000e-11
GCST008916_2	Asthma	2.000000e-08

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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Niclosamide	increases expression	2
Oxygen	increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression	1
chloroquine diphosphate	decreases expression	1
avobenzone	decreases expression	1
chloropicrin	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
bisphenol S	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases methylation	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	affects cotreatment, decreases expression	1
Gold Sodium Thiomalate	decreases expression	1
Methotrexate	decreases expression	1
Methylprednisolone	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Piroxicam	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)

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