Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT45LW1K)

DOT Name NADH-ubiquinone oxidoreductase chain 5 (ND5)
Synonyms EC 7.1.1.2; NADH dehydrogenase subunit 5
Gene Name ND5
Related Disease
Multiple sclerosis ( )
Amyotrophic lateral sclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Breast fibrocystic disease ( )
Carcinoma of esophagus ( )
Cardiovascular disease ( )
Colorectal neoplasm ( )
Esophageal cancer ( )
Glycogen storage disease due to acid maltase deficiency, infantile onset ( )
Hepatocellular carcinoma ( )
Leber hereditary optic neuropathy ( )
Liver cancer ( )
Lung adenocarcinoma ( )
Lung squamous cell carcinoma ( )
Maternally-inherited Leigh syndrome ( )
Mitochondrial encephalomyopathy ( )
Neoplasm of esophagus ( )
Nephropathy ( )
Parkinson disease ( )
Peripheral neuropathy ( )
Schizophrenia ( )
Type-1/2 diabetes ( )
Vascular disease ( )
Retinopathy ( )
Wolff-Parkinson-White syndrome ( )
Glycogen storage disease type II ( )
Leigh syndrome ( )
MELAS syndrome ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Post-traumatic stress disorder ( )
Psychotic disorder ( )
UniProt ID
NU5M_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5XTC; 5XTD; 5XTH; 5XTI
EC Number
7.1.1.2
Pfam ID
PF06455 ; PF00361 ; PF00662
Sequence
MTMHTTMTTLTLTSLIPPILTTLVNPNKKNSYPHYVKSIVASTFIISLFPTTMFMCLDQE
VIISNWHWATTQTTQLSLSFKLDYFSMMFIPVALFVTWSIMEFSLWYMNSDPNINQFFKY
LLIFLITMLILVTANNLFQLFIGWEGVGIMSFLLISWWYARADANTAAIQAILYNRIGDI
GFILALAWFILHSNSWDPQQMALLNANPSLTPLLGLLLAAAGKSAQLGLHPWLPSAMEGP
TPVSALLHSSTMVVAGIFLLIRFHPLAENSPLIQTLTLCLGAITTLFAAVCALTQNDIKK
IVAFSTSSQLGLMMVTIGINQPHLAFLHICTHAFFKAMLFMCSGSIIHNLNNEQDIRKMG
GLLKTMPLTSTSLTIGSLALAGMPFLTGFYSKDHIIETANMSYTNAWALSITLIATSLTS
AYSTRMILLTLTGQPRFPTLTNINENNPTLLNPIKRLAAGSLFAGFLITNNISPASPFQT
TIPLYLKLTALAVTFLGLLTALDLNYLTNKLKMKSPLCTFYFSNMLGFYPSITHRTIPYL
GLLTSQNLPLLLLDLTWLEKLLPKTISQHQISTSIITSTQKGMIKLYFLSFFFPLILTLL
LIT
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. Essential for the catalytic activity and assembly of complex I.
KEGG Pathway
Oxidative phosphorylation (hsa00190 )
Metabolic pathways (hsa01100 )
Thermogenesis (hsa04714 )
Retrograde endocan.binoid sig.ling (hsa04723 )
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:HS00035-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Multiple sclerosis DISB2WZI Definitive Genetic Variation [1]
Amyotrophic lateral sclerosis DISF7HVM Strong Genetic Variation [2]
Breast cancer DIS7DPX1 Strong Genetic Variation [3]
Breast carcinoma DIS2UE88 Strong Genetic Variation [3]
Breast fibrocystic disease DISUM7ID Strong Genetic Variation [3]
Carcinoma of esophagus DISS6G4D Strong Genetic Variation [4]
Cardiovascular disease DIS2IQDX Strong Genetic Variation [5]
Colorectal neoplasm DISR1UCN Strong Genetic Variation [6]
Esophageal cancer DISGB2VN Strong Genetic Variation [4]
Glycogen storage disease due to acid maltase deficiency, infantile onset DISQE1VS Strong Genetic Variation [7]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [8]
Leber hereditary optic neuropathy DIS7Y2EE Strong Genetic Variation [9]
Liver cancer DISDE4BI Strong Biomarker [8]
Lung adenocarcinoma DISD51WR Strong Altered Expression [10]
Lung squamous cell carcinoma DISXPIBD Strong Altered Expression [10]
Maternally-inherited Leigh syndrome DISGE06V Strong GermlineCausalMutation [11]
Mitochondrial encephalomyopathy DISA6PTN Strong Genetic Variation [12]
Neoplasm of esophagus DISOLKAQ Strong Genetic Variation [4]
Nephropathy DISXWP4P Strong Genetic Variation [13]
Parkinson disease DISQVHKL Strong Genetic Variation [14]
Peripheral neuropathy DIS7KN5G Strong Genetic Variation [15]
Schizophrenia DISSRV2N Strong Genetic Variation [16]
Type-1/2 diabetes DISIUHAP Strong Genetic Variation [15]
Vascular disease DISVS67S Strong Genetic Variation [17]
Retinopathy DISB4B0F moderate Genetic Variation [18]
Wolff-Parkinson-White syndrome DISW4TQ8 moderate Genetic Variation [19]
Glycogen storage disease type II DISXZPBC Limited Genetic Variation [20]
Leigh syndrome DISWQU45 Limited Genetic Variation [21]
MELAS syndrome DIS81Z3S Limited Genetic Variation [22]
Neoplasm DISZKGEW Limited Genetic Variation [23]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [24]
Post-traumatic stress disorder DISHL1EY Limited Genetic Variation [25]
Psychotic disorder DIS4UQOT Limited Genetic Variation [26]
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⏷ Show the Full List of 33 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of NADH-ubiquinone oxidoreductase chain 5 (ND5). [27]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of NADH-ubiquinone oxidoreductase chain 5 (ND5). [28]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of NADH-ubiquinone oxidoreductase chain 5 (ND5). [29]
Marinol DM70IK5 Approved Marinol decreases the expression of NADH-ubiquinone oxidoreductase chain 5 (ND5). [30]
Zidovudine DM4KI7O Approved Zidovudine increases the expression of NADH-ubiquinone oxidoreductase chain 5 (ND5). [31]
Nefazodone DM4ZS8M Approved Nefazodone decreases the expression of NADH-ubiquinone oxidoreductase chain 5 (ND5). [32]
INX-189 DMSTJ6Q Phase 2 INX-189 decreases the expression of NADH-ubiquinone oxidoreductase chain 5 (ND5). [33]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of NADH-ubiquinone oxidoreductase chain 5 (ND5). [34]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of NADH-ubiquinone oxidoreductase chain 5 (ND5). [35]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of NADH-ubiquinone oxidoreductase chain 5 (ND5). [36]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A increases the expression of NADH-ubiquinone oxidoreductase chain 5 (ND5). [37]
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⏷ Show the Full List of 11 Drug(s)

References

1 mtDNA nt13708A variant increases the risk of multiple sclerosis.PLoS One. 2008 Feb 13;3(2):e1530. doi: 10.1371/journal.pone.0001530.
2 De novo single-nucleotide and copy number variation in discordant monozygotic twins reveals disease-related genes. Eur J Hum Genet. 2019 Jul;27(7):1121-1133. doi: 10.1038/s41431-019-0376-7. Epub 2019 Mar 18.
3 Evaluating mitochondrial DNA in patients with breast cancer and benign breast disease.J Cancer Res Clin Oncol. 2011 Apr;137(4):669-75. doi: 10.1007/s00432-010-0912-x. Epub 2010 Jun 16.
4 High incidence of coding gene mutations in mitochondrial DNA in esophageal cancer.Mol Med Rep. 2017 Dec;16(6):8537-8541. doi: 10.3892/mmr.2017.7663. Epub 2017 Sep 29.
5 Analysis of mitochondrial DNA heteroplasmic mutations A1555G, C3256T, T3336C, 5178, G12315A, G13513A, G14459A, G14846 and G15059A in CHD patients with the history of myocardial infarction.Exp Mol Pathol. 2016 Feb;100(1):87-91. doi: 10.1016/j.yexmp.2015.12.003. Epub 2015 Dec 3.
6 PGC-1alpha/beta upregulation is associated with improved oxidative phosphorylation in cells harboring nonsense mtDNA mutations.Hum Mol Genet. 2007 Apr 15;16(8):993-1005. doi: 10.1093/hmg/ddm045. Epub 2007 Mar 6.
7 A novel m.12908T>a mutation in the mitochondrial ND5 gene in patient with infantile-onset Pompe disease.Biochem Biophys Res Commun. 2012 Dec 7;429(1-2):31-8. doi: 10.1016/j.bbrc.2012.10.105. Epub 2012 Nov 3.
8 Increased level of the mitochondrial ND5 transcript in chemically induced rat hepatomas.Exp Cell Res. 1989 Sep;184(1):158-66. doi: 10.1016/0014-4827(89)90374-1.
9 Leber's hereditary optic neuropathy (LHON)-associated ND5 12338T?C mutation altered the assembly and function of complex I, apoptosis and mitophagy.Hum Mol Genet. 2018 Jun 1;27(11):1999-2011. doi: 10.1093/hmg/ddy107.
10 Dissecting the expression landscape of mitochondrial genes in lung squamous cell carcinoma and lung adenocarcinoma.Oncol Lett. 2018 Sep;16(3):3992-4000. doi: 10.3892/ol.2018.9113. Epub 2018 Jul 10.
11 Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh's disease.Ann Neurol. 2003 Oct;54(4):473-8. doi: 10.1002/ana.10687.
12 Clinical and Neuroimaging Features in Two Children with Mutations in the Mitochondrial ND5 Gene.Neuropediatrics. 2015 Aug;46(4):277-81. doi: 10.1055/s-0035-1550149. Epub 2015 May 14.
13 Adult onset tubulo-interstitial nephropathy in MT-ND5-related phenotypes.Clin Genet. 2020 Apr;97(4):628-633. doi: 10.1111/cge.13670. Epub 2020 Jan 9.
14 A missense MT-ND5 mutation in differentiated Parkinson Disease cytoplasmic hybrid induces ROS-dependent DNA Damage Response amplified by DROSHA.Sci Rep. 2017 Aug 25;7(1):9528. doi: 10.1038/s41598-017-09910-x.
15 Novel mutations in ATPase 8, ND1 and ND5 genes associated with peripheral neuropathy of diabetes.Diabetes Res Clin Pract. 2014 Mar;103(3):e49-52. doi: 10.1016/j.diabres.2013.12.015. Epub 2014 Jan 5.
16 Systematic association studies of mitochondrial DNA variations in schizophrenia: focus on the ND5 gene.Schizophr Bull. 2008 May;34(3):458-65. doi: 10.1093/schbul/sbm100. Epub 2007 Sep 26.
17 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.
18 Whole mitochondrial genome screening of a family with maternally inherited diabetes and deafness (MIDD) associated with retinopathy: A putative haplotype associated to MIDD and a novel MT-CO2 m.8241T>G mutation.J Diabetes Complications. 2017 Jan;31(1):253-259. doi: 10.1016/j.jdiacomp.2016.06.028. Epub 2016 Jul 1.
19 Mutation of mitochondrial DNA G13513A presenting with Leigh syndrome, Wolff-Parkinson-White syndrome and cardiomyopathy.Pediatr Neonatol. 2008 Aug;49(4):145-9. doi: 10.1016/S1875-9572(08)60030-3.
20 Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1).Biomolecules. 2015 Oct 16;5(4):2758-81. doi: 10.3390/biom5042758.
21 Genetic heterogeneity of mitochondrial genome in thiamine deficient Leigh syndrome patients.J Neurol Sci. 2019 Sep 15;404:91-100. doi: 10.1016/j.jns.2019.07.007. Epub 2019 Jul 10.
22 A novel mutation in the mitochondrial MT-ND5 gene in a family with MELAS. The relevance of genetic analysis on targeted tissues.Mitochondrion. 2020 Jan;50:14-18. doi: 10.1016/j.mito.2019.10.001. Epub 2019 Oct 19.
23 Somatic mitochondrial DNA mutations in human chromophobe renal cell carcinomas.Genes Chromosomes Cancer. 2002 Nov;35(3):256-60. doi: 10.1002/gcc.10118.
24 The effect of very-low-calorie diet on mitochondrial dysfunction in subcutaneous adipose tissue and peripheral monocytes of obese subjects with type 2 diabetes mellitus.Physiol Res. 2017 Nov 24;66(5):811-822. doi: 10.33549/physiolres.933469. Epub 2017 Jul 18.
25 Mitochondrial genetic variants identified to be associated with posttraumatic stress disorder.Transl Psychiatry. 2015 Mar 10;5(3):e524. doi: 10.1038/tp.2015.18.
26 Mitochondrial DNA sequence data reveals association of haplogroup U with psychosis in bipolar disorder.J Psychiatr Res. 2017 Jan;84:221-226. doi: 10.1016/j.jpsychires.2016.09.027. Epub 2016 Sep 30.
27 Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
28 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
29 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.
30 Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
31 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.
32 Involvement of mitochondrial dysfunction in nefazodone-induced hepatotoxicity. Food Chem Toxicol. 2016 Aug;94:148-58. doi: 10.1016/j.fct.2016.06.001. Epub 2016 Jun 8.
33 Effects of BMS-986094, a Guanosine Nucleotide Analogue, on Mitochondrial DNA Synthesis and Function. Toxicol Sci. 2016 Oct;153(2):396-408. doi: 10.1093/toxsci/kfw135. Epub 2016 Jul 27.
34 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
35 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
36 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
37 In vitro blood brain barrier exposure to mycotoxins and carotenoids pumpkin extract alters mitochondrial gene expression and oxidative stress. Food Chem Toxicol. 2021 Jul;153:112261. doi: 10.1016/j.fct.2021.112261. Epub 2021 May 17.