NDUFA11

Summary

NDUFA11 (NADH:ubiquinone oxidoreductase subunit A11, HGNC:20371) is a protein-coding gene on chromosome 19p13.3, encoding NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 (Q86Y39). 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: 54.8% of cell lines).

This gene encodes a subunit of the membrane-bound mitochondrial complex I. Complex I is composed of numerous subunits and functions as the NADH-ubiquinol reductase of the mitochondrial electron transport chain. Mutations in this gene are associated with severe mitochondrial complex I deficiency. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 126328 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial complex I deficiency, nuclear type 14 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 118 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 48
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 54.8% of screened cell lines
• MANE Select transcript: NM_175614

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20371
Approved symbol	NDUFA11
Name	NADH:ubiquinone oxidoreductase subunit A11
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	B14.7
Ensembl gene	ENSG00000174886
Ensembl biotype	protein_coding
OMIM	612638
Entrez	126328

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000308961, ENST00000418389, ENST00000591160, ENST00000591341, ENST00000592634, ENST00000593233, ENST00000650663, ENST00000896896, ENST00000896897, ENST00000919896, ENST00000919897, ENST00000919898

RefSeq mRNA: 2 — MANE Select: NM_175614 NM_001193375, NM_175614

CCDS: CCDS12155, CCDS54203

Canonical transcript exons

ENST00000308961 — 4 exons

Exon	Start	End
ENSE00002822786	5903612	5903790
ENSE00003554526	5896453	5896575
ENSE00003606658	5896905	5896997
ENSE00003616390	5894675	5894854

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 99.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 260.3438 / max 1064.4732, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178577	259.2542	1827
178578	0.9822	638
178579	0.1074	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.82	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.62	gold quality
left ventricle myocardium	UBERON:0006566	99.49	gold quality
cardiac atrium	UBERON:0002081	99.45	gold quality
right atrium auricular region	UBERON:0006631	99.45	gold quality
apex of heart	UBERON:0002098	99.34	gold quality
heart left ventricle	UBERON:0002084	99.25	gold quality
left adrenal gland cortex	UBERON:0035825	99.24	gold quality
left adrenal gland	UBERON:0001234	99.23	gold quality
cardiac ventricle	UBERON:0002082	99.23	gold quality
right adrenal gland	UBERON:0001233	99.22	gold quality
adrenal cortex	UBERON:0001235	99.22	gold quality
upper arm skin	UBERON:0004263	99.22	gold quality
kidney epithelium	UBERON:0004819	99.21	gold quality
right adrenal gland cortex	UBERON:0035827	99.17	gold quality
ileal mucosa	UBERON:0000331	99.15	gold quality
myocardium	UBERON:0002349	99.12	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.09	gold quality
lower esophagus	UBERON:0013473	99.08	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.08	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.04	gold quality
hypothalamus	UBERON:0001898	99.00	gold quality
heart	UBERON:0000948	98.99	gold quality
body of tongue	UBERON:0011876	98.99	gold quality
renal medulla	UBERON:0000362	98.97	gold quality
mucosa of transverse colon	UBERON:0004991	98.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.92	gold quality
lower esophagus mucosa	UBERON:0035834	98.92	gold quality
prefrontal cortex	UBERON:0000451	98.89	gold quality
adenohypophysis	UBERON:0002196	98.87	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	18.65
E-MTAB-10042	yes	10.73
E-MTAB-7316	yes	7.32
E-MTAB-7606	no	875.10
E-CURD-10	no	424.39
E-MTAB-6058	no	178.52

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 54.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• study identified a splice-site mutation in the NDUFA11 gene in six mitochondrial complex I deficiency patients from three unrelated families (PMID:18306244)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufa11	ENSDARG00000042777
mus_musculus	Ndufa11	ENSMUSG00000002379
rattus_norvegicus	Ndufa11	ENSRNOG00000048320
drosophila_melanogaster	ND-B14.7	FBGN0034576

Protein

Protein identifiers

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 — Q86Y39 (reviewed: Q86Y39)

Alternative names: Complex I-B14.7, NADH-ubiquinone oxidoreductase subunit B14.7

All UniProt accessions (2): Q86Y39, K7EQ77

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 14 (MC1DN14) [MIM:618236] 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. MC1DN14 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 NDUFA11 subunit family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86Y39-1	1	yes
Q86Y39-2	2

RefSeq proteins (2): NP_001180304, NP_783313* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039205	NDUFA11	Family

UniProt features (8 total): transmembrane region 2, sequence conflict 2, initiator methionine 1, chain 1, modified residue 1, splice variant 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-Q86Y39-F1	89.44	0.65

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): 2

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

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

MSigDB gene sets: 240 (showing top): E2F_Q4_01, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, E2F_Q3, GOBP_ATP_BIOSYNTHETIC_PROCESS, GOBP_OXIDATIVE_PHOSPHORYLATION, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (3): mitochondrial electron transport, NADH to ubiquinone (GO:0006120), aerobic respiration (GO:0009060), proton motive force-driven mitochondrial ATP synthesis (GO:0042776)

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

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), respiratory chain complex I (GO:0045271), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
cellular respiration	1
mitochondrion	1
oxidative phosphorylation	1
proton motive force-driven ATP synthesis	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
NADH dehydrogenase complex	1
respiratory chain complex	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDUFA11	NDUFS8	O00217	912
NDUFA11	UQCRQ	O14949	909
NDUFA11	NDUFS7	O75251	891
NDUFA11	NDUFA1	O15239	875
NDUFA11	NDUFS2	O75306	869
NDUFA11	NDUFB9	Q9Y6M9	864
NDUFA11	NDUFV1	P49821	864
NDUFA11	NDUFA2	O43678	857
NDUFA11	NDUFV2	P19404	849
NDUFA11	NDUFS1	P28331	814
NDUFA11	NDUFB5	O43674	787
NDUFA11	NDUFB3	O43676	787
NDUFA11	NDUFS6	O75380	784
NDUFA11	MT-ND5	P03915	783
NDUFA11	NDUFAF4	Q9P032	765

IntAct

26 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
MEOX2	NDUFA11	psi-mi:“MI:0915”(physical association)	0.560
NDUFS5	NDUFS8	psi-mi:“MI:0914”(association)	0.530
NDUFA9	NDUFS8	psi-mi:“MI:0914”(association)	0.530
NDUFA2	NDUFS8	psi-mi:“MI:0915”(physical association)	0.400
NDUFA12	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFS4	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA11	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA6	NDUFS8	psi-mi:“MI:0914”(association)	0.350
FOXC1	NFIX	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
FAM136A	IDE	psi-mi:“MI:0914”(association)	0.350
NDUFS3	ACOT7	psi-mi:“MI:0914”(association)	0.350
NMES1	COX7A2L	psi-mi:“MI:0914”(association)	0.350
NDUFB11	NDUFS8	psi-mi:“MI:0914”(association)	0.350
GAA	ADAM10	psi-mi:“MI:0914”(association)	0.350
SLC25A1	CYC1	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
SLC25A32	CS	psi-mi:“MI:0914”(association)	0.350
NDUFA11	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (71): NDUFA11 (Affinity Capture-MS), NDUFA11 (Affinity Capture-MS), NDUFA11 (Affinity Capture-MS), NDUFA11 (Affinity Capture-MS), NDUFA11 (Affinity Capture-MS), NDUFA9 (Affinity Capture-MS), NDUFA8 (Affinity Capture-MS), NIT1 (Affinity Capture-MS), ND5 (Affinity Capture-MS), NDUFA6 (Affinity Capture-MS), NDUFV3 (Affinity Capture-MS), YME1L1 (Affinity Capture-MS), NDUFV2 (Affinity Capture-MS), NDUFS4 (Affinity Capture-MS), NDUFB6 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D8PI78, A1XJK0, A1XQR6, A2RVP7, A4QNF3, O44477, O48528, P0CR88, P0CR89, P25710, P32897, P60602, P60603, P79082, P81928, P87130, P87146, Q02889, Q0MQB8, Q0MQB9, Q0MQC0, Q12328, Q2UAP8, Q38820, Q3SZV8, Q4V7T9, Q54QM0, Q5NVQ1, Q6BT35, Q6BZY4, Q6CRJ6, Q6FT37, Q6NYD1, Q75E80, Q7T2P6, Q80W89, Q86Y39, Q8HXG6, Q8IN78, Q9C1E8

Diamond homologs: Q0MQB8, Q0MQB9, Q0MQC0, Q80W89, Q86Y39, Q8HXG6, Q9D8B4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NDUFA11	“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 27 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	10	72.0×	3e-15
Respiratory electron transport	11	45.5×	5e-15
Aerobic respiration and respiratory electron transport	9	34.6×	4e-11

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	7	100.4×	2e-11
proton motive force-driven mitochondrial ATP synthesis	9	94.8×	3e-14
aerobic respiration	9	89.2×	3e-14
mitochondrial respiratory chain complex I assembly	5	82.2×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	50
Likely benign	35
Benign	17

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
214694	NM_175614.5(NDUFA11):c.314-2A>G	Pathogenic
3584071	NM_001193375.3(NDUFA11):c.314-3_325delinsAGAT	Likely pathogenic
372670	NM_175614.5(NDUFA11):c.313+1G>A	Likely pathogenic

SpliceAI

1131 predictions. Top by Δscore:

Variant	Effect	Δscore
19:5896451:A:AC	donor_gain	1.0000
19:5896451:ACTG:A	donor_gain	1.0000
19:5896452:C:CT	donor_gain	1.0000
19:5896452:CTG:C	donor_gain	1.0000
19:5896452:CTGC:C	donor_gain	1.0000
19:5896461:C:CA	donor_gain	1.0000
19:5896993:CAGGC:C	acceptor_gain	1.0000
19:5896994:AGGC:A	acceptor_gain	1.0000
19:5896995:GGC:G	acceptor_gain	1.0000
19:5896995:GGCC:G	acceptor_loss	1.0000
19:5896998:C:CC	acceptor_gain	1.0000
19:5896998:CTGC:C	acceptor_loss	1.0000
19:5903606:GCTCA:G	donor_loss	1.0000
19:5903608:TCA:T	donor_loss	1.0000
19:5903609:CA:C	donor_loss	1.0000
19:5903609:CAC:C	donor_loss	1.0000
19:5903610:A:AC	donor_gain	1.0000
19:5903611:C:CA	donor_loss	1.0000
19:5903611:C:CC	donor_gain	1.0000
19:5903611:C:CT	donor_loss	1.0000
19:5903628:A:AC	donor_gain	1.0000
19:5903629:C:CC	donor_gain	1.0000
19:5894853:CG:C	acceptor_gain	0.9900
19:5894855:C:CC	acceptor_gain	0.9900
19:5896444:GCCAC:G	donor_loss	0.9900
19:5896445:CCACT:C	donor_loss	0.9900
19:5896446:CACTC:C	donor_loss	0.9900
19:5896447:AC:A	donor_loss	0.9900
19:5896448:C:G	donor_loss	0.9900
19:5896449:T:TA	donor_loss	0.9900

AlphaMissense

900 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:5896535:G:C	S77R	0.991
19:5896535:G:T	S77R	0.991
19:5896537:T:G	S77R	0.991
19:5896499:G:C	N89K	0.988
19:5896499:G:T	N89K	0.988
19:5894812:C:T	G119D	0.987
19:5896479:G:T	A96D	0.987
19:5903619:G:C	S30R	0.987
19:5903619:G:T	S30R	0.987
19:5903621:T:G	S30R	0.987
19:5896572:G:T	A65D	0.986
19:5894825:A:G	C115R	0.985
19:5896556:A:C	F70L	0.985
19:5896556:A:T	F70L	0.985
19:5896558:A:G	F70L	0.985
19:5896575:G:T	A64D	0.985
19:5896563:G:T	A68D	0.984
19:5894813:C:G	G119R	0.983
19:5896483:A:G	C95R	0.983
19:5896997:C:T	G33D	0.979
19:5903612:C:G	G33R	0.978
19:5896488:C:T	G93D	0.976
19:5896567:C:G	G67R	0.976
19:5896567:C:T	G67R	0.976
19:5894824:C:T	C115Y	0.975
19:5896555:C:G	G71R	0.974
19:5896569:A:T	V66D	0.974
19:5896543:A:G	C75R	0.973
19:5896564:C:G	A68P	0.973
19:5896566:C:T	G67E	0.972

dbSNP variants (sampled 300 via entrez): RS1000161859 (19:5894200 G>A), RS1000472025 (19:5903324 C>T), RS1000775171 (19:5903161 C>A,T), RS1000805066 (19:5901430 T>C), RS1001637498 (19:5896390 C>A,T), RS1001637896 (19:5892176 C>T), RS1002046919 (19:5891350 C>T), RS1002341218 (19:5891521 A>C,G), RS1002425704 (19:5900446 G>A), RS1002458270 (19:5900187 C>T), RS1002609103 (19:5904644 C>A,T), RS1002618184 (19:5896074 A>G), RS1002757522 (19:5898660 G>A), RS1002951115 (19:5902837 C>A,G,T), RS1002976626 (19:5893286 T>A,C)

Disease associations

OMIM: gene MIM:612638 | disease phenotypes: MIM:252010, MIM:618236

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex I deficiency, nuclear type 14	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	Limited	AR

Mondo (3): mitochondrial complex I deficiency, nuclear type 1 (MONDO:0100224), mitochondrial complex I deficiency, nuclear type 14 (MONDO:0032619), mitochondrial complex I deficiency (MONDO:0100133)

Orphanet (0):

HPO phenotypes

48 total (30 of 48 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000114	Proximal tubulopathy
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000543	Optic disc pallor
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000817	Reduced eye contact
HP:0000819	Diabetes mellitus
HP:0001138	Optic neuropathy
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001639	Hypertrophic cardiomyopathy
HP:0001943	Hypoglycemia
HP:0002013	Vomiting
HP:0002093	Respiratory insufficiency
HP:0002104	Apnea
HP:0002151	Increased circulating lactate concentration
HP:0002240	Hepatomegaly

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST004732_2	Heart rate variability traits (pvRSA/HF)	5.000000e-41
GCST004732_3	Heart rate variability traits (pvRSA/HF)	2.000000e-41
GCST004733_1	Heart rate variability traits (RMSSD)	4.000000e-46
GCST004733_13	Heart rate variability traits (RMSSD)	2.000000e-63
GCST004734_12	Heart rate variability traits (SDNN)	2.000000e-23
GCST004734_2	Heart rate variability traits (SDNN)	2.000000e-23
GCST004734_3	Heart rate variability traits (SDNN)	2.000000e-24
GCST005787_14	Heart rate response to exercise	2.000000e-06
GCST005788_18	Heart rate response to recovery post exercise	2.000000e-09
GCST005846_15	Heart rate response to recovery post exercise (10 sec)	1.000000e-10
GCST005847_16	Heart rate response to recovery post exercise (20 sec)	7.000000e-09
GCST005848_6	Heart rate response to recovery post exercise (50 sec)	2.000000e-09
GCST005849_8	Heart rate response to recovery post exercise (40 sec)	9.000000e-10
GCST005850_14	Heart rate response to recovery post exercise (30 sec)	4.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008003	heart rate variability measurement
EFO:0009184	heart rate response to exercise
EFO:0009185	heart rate response to recovery post exercise

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Particulate Matter	affects expression, increases abundance, affects cotreatment, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tris(chloroethyl)phosphate	decreases expression, increases abundance	1
chloropicrin	decreases expression	1
K 7174	decreases expression	1
ICG 001	increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Doxorubicin	increases expression	1
Flame Retardants	increases abundance, decreases expression	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	decreases expression	1
1-Butanol	increases expression, affects cotreatment, increases abundance	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

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3C0	Abcam HEK293T NDUFA11 KO	Transformed cell line	Female

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)