Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEVK4WW)

DOT Name	NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1)
Synonyms	NDUFV1; EC 7.1.1.2; Complex I-51kD; CI-51kD; NADH dehydrogenase flavoprotein 1; NADH-ubiquinone oxidoreductase 51 kDa subunit
Gene Name	NDUFV1
Related Disease	Leigh syndrome ( ) Mitochondrial complex 1 deficiency, nuclear type 4 ( ) Mitochondrial complex I deficiency, nuclear type 1 ( ) Autism spectrum disorder ( ) Bipolar disorder ( ) Gastric cancer ( ) Gastric neoplasm ( ) Hereditary diffuse gastric adenocarcinoma ( ) Major depressive disorder ( ) MELAS syndrome ( ) Mitochondrial disease ( ) Mitochondrial myopathy ( ) Nervous system disease ( ) Schizophrenia ( ) Vascular disease ( ) Mitochondrial complex I deficiency ( ) Obsolete Leigh syndrome with leukodystrophy ( ) Leukodystrophy ( ) Osteoarthritis ( )
UniProt ID	NDUV1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	5XTB; 5XTD; 5XTH; 5XTI
EC Number	7.1.1.2
Pfam ID	PF01512 ; PF10589
Sequence	MLATRRLLGWSLPARVSVRFSGDTTAPKKTSFGSLKDEDRIFTNLYGRHDWRLKGSLSRG DWYKTKEILLKGPDWILGEIKTSGLRGRGGAGFPTGLKWSFMNKPSDGRPKYLVVNADEG EPGTCKDREILRHDPHKLLEGCLVGGRAMGARAAYIYIRGEFYNEASNLQVAIREAYEAG LIGKNACGSGYDFDVFVVRGAGAYICGEETALIESIEGKQGKPRLKPPFPADVGVFGCPT TVANVETVAVSPTICRRGGTWFAGFGRERNSGTKLFNISGHVNHPCTVEEEMSVPLKELI EKHAGGVTGGWDNLLAVIPGGSSTPLIPKSVCETVLMDFDALVQAQTGLGTAAVIVMDRS TDIVKAIARLIEFYKHESCGQCTPCREGVDWMNKVMARFVRGDARPAEIDSLWEISKQIE GHTICALGDGAAWPVQGLIRHFRPELEERMQRFAQQHQARQAAS
Function	Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Part of the peripheral arm of the enzyme, where the electrons from NADH are accepted by flavin mononucleotide (FMN) and then passed along a chain of iron-sulfur clusters by electron tunnelling to the final acceptor ubiquinone. Contains FMN, which is the initial electron acceptor as well as one iron-sulfur cluster.
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:HS09641-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Leigh syndrome	DISWQU45	Definitive	Autosomal recessive	[1]
Mitochondrial complex 1 deficiency, nuclear type 4	DISA4S68	Definitive	Autosomal recessive	[2]
Mitochondrial complex I deficiency, nuclear type 1	DISCPLX4	Definitive	Autosomal recessive	[3]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[4]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[6]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[6]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[7]
MELAS syndrome	DIS81Z3S	Strong	Genetic Variation	[8]
Mitochondrial disease	DISKAHA3	Strong	Biomarker	[9]
Mitochondrial myopathy	DIS9SA7V	Strong	Biomarker	[10]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[11]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[12]
Vascular disease	DISVS67S	Strong	Genetic Variation	[8]
Mitochondrial complex I deficiency	DIS13M7V	Supportive	Autosomal recessive	[13]
Obsolete Leigh syndrome with leukodystrophy	DISABU9D	Supportive	Autosomal recessive	[14]
Leukodystrophy	DISVY1TT	Limited	Biomarker	[15]
Osteoarthritis	DIS05URM	Limited	Biomarker	[16]
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⏷ Show the Full List of 19 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

15 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 flavoprotein 1, mitochondrial (NDUFV1).	[17]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[19]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[20]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[21]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[23]
Selenium	DM25CGV	Approved	Selenium increases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[24]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[25]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[26]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[27]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[28]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[30]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[20]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[31]
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⏷ Show the Full List of 15 Drug(s)

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1).	[29]
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References

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2	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
3	Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
4	Using extended pedigrees to identify novel autism spectrum disorder (ASD) candidate genes.Hum Genet. 2015 Feb;134(2):191-201. doi: 10.1007/s00439-014-1513-6. Epub 2014 Nov 29.
5	Mitochondrial complex I and III mRNA levels in bipolar disorder.J Affect Disord. 2015 Sep 15;184:160-3. doi: 10.1016/j.jad.2015.05.060. Epub 2015 Jun 10.
6	A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
7	Neuroanatomical pattern of mitochondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression.PLoS One. 2008;3(11):e3676. doi: 10.1371/journal.pone.0003676. Epub 2008 Nov 7.
8	Outcome of epilepsy in patients with mitochondrial disorders: Phenotype genotype and magnetic resonance imaging correlations.Clin Neurol Neurosurg. 2018 Jan;164:182-189. doi: 10.1016/j.clineuro.2017.12.010. Epub 2017 Dec 9.
9	Advantages and pitfalls of an extended gene panel for investigating complex neurometabolic phenotypes.Brain. 2016 Nov 1;139(11):2844-2854. doi: 10.1093/brain/aww221.
10	Cloning of the human mitochondrial 51 kDa subunit (NDUFV1) reveals a 100% antisense homology of its 3'UTR with the 5'UTR of the gamma-interferon inducible protein (IP-30) precursor: is this a link between mitochondrial myopathy and inflammation?.Biochem Biophys Res Commun. 1998 Apr 17;245(2):599-606. doi: 10.1006/bbrc.1998.8486.
11	Targeted exome sequencing of suspected mitochondrial disorders. Neurology. 2013 May 7;80(19):1762-70. doi: 10.1212/WNL.0b013e3182918c40. Epub 2013 Apr 17.
12	Sp1 expression is disrupted in schizophrenia; a possible mechanism for the abnormal expression of mitochondrial complex I genes, NDUFV1 and NDUFV2.PLoS One. 2007 Sep 5;2(9):e817. doi: 10.1371/journal.pone.0000817.
13	Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects: what we learned from 130 cases. J Inherit Metab Dis. 2012 Sep;35(5):737-47. doi: 10.1007/s10545-012-9492-z. Epub 2012 May 30.
14	A novel NDUFV1 gene mutation in complex I deficiency in consanguineous siblings with brainstem lesions and Leigh syndrome. Clin Genet. 2012 Sep;82(3):264-70. doi: 10.1111/j.1399-0004.2011.01743.x. Epub 2011 Jul 18.
15	Cystic Leucoencephalopathy in NDUFV1 Mutation.Indian J Pediatr. 2018 Dec;85(12):1128-1131. doi: 10.1007/s12098-018-2721-1. Epub 2018 Jun 9.
16	Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance.Mol Cell Proteomics. 2009 Jan;8(1):172-89. doi: 10.1074/mcp.M800292-MCP200. Epub 2008 Sep 9.
17	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
18	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.
19	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
20	Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
21	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
22	Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
23	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.
24	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
25	New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids. Arch Toxicol. 2021 Aug;95(8):2691-2718. doi: 10.1007/s00204-021-03092-2. Epub 2021 Jun 20.
26	Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells. Acta Pharmacol Sin. 2004 Mar;25(3):378-84.
27	Morphological and molecular course of mitochondrial pathology in cultured human cells exposed long-term to Zidovudine. Environ Mol Mutagen. 2007 Apr-May;48(3-4):179-89. doi: 10.1002/em.20245.
28	Beneficial effects of resveratrol on respiratory chain defects in patients' fibroblasts involve estrogen receptor and estrogen-related receptor alpha signaling. Hum Mol Genet. 2014 Apr 15;23(8):2106-19.
29	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
30	Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
31	CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.