Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM2T1FI)

DOT Name Ubiquinone biosynthesis protein COQ9, mitochondrial (COQ9)
Gene Name COQ9
Related Disease
Coenzyme Q10 deficiency, primary, 1 ( )
Mitochondrial disease ( )
Steroid-resistant nephrotic syndrome ( )
Coenzyme Q10 deficiency ( )
Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome ( )
Hyperthyroidism ( )
Hypothyroidism ( )
Inborn error of metabolism ( )
Metabolic disorder ( )
Lactic acidosis ( )
Leigh syndrome ( )
Type-1/2 diabetes ( )
UniProt ID
COQ9_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4RHP; 6AWL; 6DEW; 7SSP; 7SSS
Pfam ID
PF08511 ; PF21392
Sequence
MAAAAVSGALGRAGWRLLQLRCLPVARCRQALVPRAFHASAVGLRSSDEQKQQPPNSFSQ
QHSETQGAEKPDPESSHSPPRYTDQGGEEEEDYESEEQLQHRILTAALEFVPAHGWTAEA
IAEGAQSLGLSSAAASMFGKDGSELILHFVTQCNTRLTRVLEEEQKLVQLGQAEKRKTDQ
FLRDAVETRLRMLIPYIEHWPRALSILMLPHNIPSSLSLLTSMVDDMWHYAGDQSTDFNW
YTRRAMLAAIYNTTELVMMQDSSPDFEDTWRFLENRVNDAMNMGHTAKQVKSTGEALVQG
LMGAAVTLKNLTGLNQRR
Function
Lipid-binding protein involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration. Binds a phospholipid of at least 10 carbons in each acyl group. May be required to present its bound-lipid to COQ7.
Reactome Pathway
Ubiquinol biosynthesis (R-HSA-2142789 )

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Coenzyme Q10 deficiency, primary, 1 DISD9V13 Definitive Autosomal recessive [1]
Mitochondrial disease DISKAHA3 Definitive Autosomal recessive [2]
Steroid-resistant nephrotic syndrome DISVEBC9 Definitive Biomarker [3]
Coenzyme Q10 deficiency DIS1HGDF Strong Genetic Variation [4]
Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome DIS7ZKT7 Strong Autosomal recessive [1]
Hyperthyroidism DISX87ZH Strong Biomarker [5]
Hypothyroidism DISR0H6D Strong Biomarker [5]
Inborn error of metabolism DISO5FAY Strong Genetic Variation [4]
Metabolic disorder DIS71G5H Strong Biomarker [6]
Lactic acidosis DISZI1ZK Limited Genetic Variation [7]
Leigh syndrome DISWQU45 Limited Autosomal recessive [2]
Type-1/2 diabetes DISIUHAP Limited Biomarker [8]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 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 Ubiquinone biosynthesis protein COQ9, mitochondrial (COQ9). [9]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Ubiquinone biosynthesis protein COQ9, mitochondrial (COQ9). [10]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Ubiquinone biosynthesis protein COQ9, mitochondrial (COQ9). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Ubiquinone biosynthesis protein COQ9, mitochondrial (COQ9). [12]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Ubiquinone biosynthesis protein COQ9, mitochondrial (COQ9). [13]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Ubiquinone biosynthesis protein COQ9, mitochondrial (COQ9). [14]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of Ubiquinone biosynthesis protein COQ9, mitochondrial (COQ9). [15]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Ubiquinone biosynthesis protein COQ9, mitochondrial (COQ9). [16]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Ubiquinone biosynthesis protein COQ9, mitochondrial (COQ9). [17]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Ubiquinone biosynthesis protein COQ9, mitochondrial (COQ9). [18]
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⏷ Show the Full List of 10 Drug(s)

References

1 A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease. Am J Hum Genet. 2009 May;84(5):558-66. doi: 10.1016/j.ajhg.2009.03.018. Epub 2009 Apr 16.
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 Genetic bases and clinical manifestations of coenzyme Q10 (CoQ 10) deficiency.J Inherit Metab Dis. 2015 Jan;38(1):145-56. doi: 10.1007/s10545-014-9749-9. Epub 2014 Aug 5.
4 A rare case of primary coenzyme Q10 deficiency due to COQ9 mutation.J Pediatr Endocrinol Metab. 2020 Jan 28;33(1):165-170. doi: 10.1515/jpem-2019-0245.
5 Thyroid state affects H(2)O(2) removal by rat heart mitochondria.Arch Biochem Biophys. 2019 Feb 15;662:61-67. doi: 10.1016/j.abb.2018.11.025. Epub 2018 Nov 30.
6 A family segregating lethal neonatal coenzyme Q(10) deficiency caused by mutations in COQ9.J Inherit Metab Dis. 2018 Jul;41(4):719-729. doi: 10.1007/s10545-017-0122-7. Epub 2018 Mar 20.
7 Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9.Eur J Hum Genet. 2016 Mar;24(3):450-4. doi: 10.1038/ejhg.2015.133. Epub 2015 Jun 17.
8 Therapeutic targeting of oxidative stress with coenzyme Q10 counteracts exaggerated diabetic cardiomyopathy in a mouse model of diabetes with diminished PI3K(p110) signaling.Free Radic Biol Med. 2015 Oct;87:137-47. doi: 10.1016/j.freeradbiomed.2015.04.028. Epub 2015 Apr 30.
9 Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
10 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.
11 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.
12 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.
13 Effect of mitochondrial dysfunction and oxidative stress on endogenous levels of coenzyme Q(10) in human cells. J Biochem Mol Toxicol. 2011 Sep-Oct;25(5):280-9. doi: 10.1002/jbt.20387. Epub 2011 Feb 9.
14 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
15 Gene expression profile of colon cancer cell lines treated with SN-38. Chemotherapy. 2010;56(1):17-25. doi: 10.1159/000287353. Epub 2010 Feb 24.
16 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
17 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.
18 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.