Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZXD1UK)

• DOT Name: NADH dehydrogenase 1 alpha subcomplex subunit 11 (NDUFA11)
• Synonyms: Complex I-B14.7; CI-B14.7; NADH-ubiquinone oxidoreductase subunit B14.7
• Gene Name: NDUFA11
• Related Disease:
  Mitochondrial complex 1 deficiency, nuclear type 14
  Mitochondrial complex I deficiency
  Mitochondrial disease
• UniProt ID: NDUAB_HUMAN
• PDB ID: 5XTC; 5XTD; 5XTH; 5XTI
• Sequence:
  MAPKVFRQYWDIPDGTDCHRKAYSTTSIASVAGLTAAAYRVTLNPPGTFLEGVAKVGQYT
  FTAAAVGAVFGLTTCISAHVREKPDDPLNYFLGGCAGGLTLGARTHNYGIGAAACVYFGI
  AASLVKMGRLEGWEVFAKPKV
• 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.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Thermogenesis (hsa04714)
  Retrograde endocan.binoid sig.ling (hsa04723)
  Non-alcoholic fatty liver disease (hsa04932)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Complex I biogenesis (R-HSA-6799198)
  Respiratory electron transport (R-HSA-611105)
• BioCyc Pathway: MetaCyc:HS16402-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial complex 1 deficiency, nuclear type 14	DIS56GKJ	Strong	Autosomal recessive	[1]
Mitochondrial complex I deficiency	DIS13M7V	Supportive	Autosomal recessive	[1]
Mitochondrial disease	DISKAHA3	Limited	Autosomal recessive	[2]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of NADH dehydrogenase 1 alpha subcomplex subunit 11 (NDUFA11).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of NADH dehydrogenase 1 alpha subcomplex subunit 11 (NDUFA11).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of NADH dehydrogenase 1 alpha subcomplex subunit 11 (NDUFA11).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of NADH dehydrogenase 1 alpha subcomplex subunit 11 (NDUFA11).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of NADH dehydrogenase 1 alpha subcomplex subunit 11 (NDUFA11).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of NADH dehydrogenase 1 alpha subcomplex subunit 11 (NDUFA11).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of NADH dehydrogenase 1 alpha subcomplex subunit 11 (NDUFA11).	[9]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of NADH dehydrogenase 1 alpha subcomplex subunit 11 (NDUFA11).	[10]

References

• [1] Mitochondrial complex I deficiency caused by a deleterious NDUFA11 mutation. Ann Neurol. 2008 Mar;63(3):405-8. doi: 10.1002/ana.21332.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [9] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [10] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.