Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2CHQQ1)

• DOT Name: NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7)
• Synonyms: Cell adhesion protein SQM1; Complex I-B18; CI-B18; NADH-ubiquinone oxidoreductase B18 subunit
• Gene Name: NDUFB7
• Related Disease: Wilson disease
• UniProt ID: NDUB7_HUMAN
• PDB ID: 5XTC; 5XTD; 5XTH; 5XTI
• Pfam ID: PF05676
• Sequence:
  MGAHLVRRYLGDASVEPDPLQMPTFPPDYGFPERKEREMVATQQEMMDAQLRLQLRDYCA
  HHLIRLLKCKRDSFPNFLACKQERHDWDYCEHRDYVMRMKEFERERRLLQRKKRREKKAA
  ELAKGQGPGEVDPKVAL
• 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:HS01908-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Wilson disease	DISVS9H7	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7) affects the response to substance of Paclitaxel.	[13]

11 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 beta subcomplex subunit 7 (NDUFB7).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7).	[7]
Fenretinide	DMRD5SP	Phase 3	Fenretinide affects the expression of NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7).	[11]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of NADH dehydrogenase 1 beta subcomplex subunit 7 (NDUFB7).	[12]

References

• [1] The early molecular processes underlying the neurological manifestations of an animal model of Wilson's disease.Metallomics. 2013 May;5(5):532-40. doi: 10.1039/c3mt20243g. Epub 2013 Mar 21.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [5] Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
• [6] 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.
• [7] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [8] 4-HPR modulates gene expression in ovarian cells. Int J Cancer. 2006 Sep 1;119(5):1005-13. doi: 10.1002/ijc.21797.
• [9] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] In vitro gene expression data supporting a DNA non-reactive genotoxic mechanism for ochratoxin A. Toxicol Appl Pharmacol. 2007 Apr 15;220(2):216-24.
• [13] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.