Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDD9G4E)

DOT Name	Inositol oxygenase (MIOX)
Synonyms	EC 1.13.99.1; Aldehyde reductase-like 6; Kidney-specific protein 32; Myo-inositol oxygenase; MI oxygenase; Renal-specific oxidoreductase
Gene Name	MIOX
Related Disease	Cryptococcosis ( ) Obesity ( ) Polycystic ovarian syndrome ( ) Type-1/2 diabetes ( ) Diabetic kidney disease ( ) Type-1 diabetes ( )
UniProt ID	MIOX_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2IBN
EC Number	1.13.99.1
Pfam ID	PF05153
Sequence	MKVTVGPDPSLVYRPDVDPEVAKDKASFRNYTSGPLLDRVFTTYKLMHTHQTVDFVRSKH AQFGGFSYKKMTVMEAVDLLDGLVDESDPDVDFPNSFHAFQTAEGIRKAHPDKDWFHLVG LLHDLGKVLALFGEPQWAVVGDTFPVGCRPQASVVFCDSTFQDNPDLQDPRYSTELGMYQ PHCGLDRVLMSWGHDEYMYQVMKFNKFSLPPEAFYMIRFHSFYPWHTGRDYQQLCSQQDL AMLPWVREFNKFDLYTKCPDLPDVDKLRPYYQGLIDKYCPGILSW
Tissue Specificity	Kidney specific.
KEGG Pathway	Ascorbate and aldarate metabolism (hsa00053 ) Inositol phosphate metabolism (hsa00562 ) Metabolic pathways (hsa01100 ) Biosynthesis of nucleotide sugars (hsa01250 )
Reactome Pathway	Synthesis of IP2, IP, and Ins in the cytosol (R-HSA-1855183 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cryptococcosis	DISDYDTK	Strong	Genetic Variation	[1]
Obesity	DIS47Y1K	Strong	Biomarker	[2]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[3]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[2]
Diabetic kidney disease	DISJMWEY	moderate	Biomarker	[4]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[5]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Inositol oxygenase (MIOX).	[6]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Inositol oxygenase (MIOX).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Inositol oxygenase (MIOX).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Inositol oxygenase (MIOX).	[9]
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References

1	Production of d-glucuronic acid from myo-inositol using Escherichia coli whole-cell biocatalyst overexpressing a novel myo-inositol oxygenase from Thermothelomyces thermophile.Enzyme Microb Technol. 2019 Aug;127:70-74. doi: 10.1016/j.enzmictec.2019.04.013. Epub 2019 Apr 24.
2	Transcriptional and Translational Modulation of myo-Inositol Oxygenase (Miox) by Fatty Acids: IMPLICATIONS IN RENAL TUBULAR INJURY INDUCED IN OBESITY AND DIABETES.J Biol Chem. 2016 Jan 15;291(3):1348-67. doi: 10.1074/jbc.M115.698191. Epub 2015 Nov 17.
3	Does myo-inositol oxygenase, the only enzyme to catalyze myo-inositol in vivo, play a role in the etiology of polycystic ovarian syndrome?.Gynecol Endocrinol. 2018 May;34(5):418-421. doi: 10.1080/09513590.2017.1409710. Epub 2017 Nov 29.
4	Contribution of myo-inositol oxygenase in AGE:RAGE-mediated renal tubulointerstitial injury in the context of diabetic nephropathy.Am J Physiol Renal Physiol. 2018 Jan 1;314(1):F107-F121. doi: 10.1152/ajprenal.00434.2017. Epub 2017 Sep 20.
5	Polymorphisms of myo-inositol oxygenase gene are associated with Type 1 diabetes mellitus.J Diabetes Complications. 2010 Nov-Dec;24(6):404-8. doi: 10.1016/j.jdiacomp.2009.09.005. Epub 2009 Nov 6.
6	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
7	Role of myo-inositol in acute kidney injury induced by cisplatin. Toxicology. 2023 Nov;499:153653. doi: 10.1016/j.tox.2023.153653. Epub 2023 Oct 18.
8	17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
9	Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.