Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6VDAAN)

• DOT Name: Retinol dehydrogenase 14 (RDH14)
• Synonyms: EC 1.1.1.300; Alcohol dehydrogenase PAN2; Short chain dehydrogenase/reductase family 7C member 4
• Gene Name: RDH14
• UniProt ID: RDH14_HUMAN
• EC Number: 1.1.1.300
• Pfam ID: PF00106
• Sequence:
  MAVATAAAVLAALGGALWLAARRFVGPRVQRLRRGGDPGLMHGKTVLITGANSGLGRATA
  AELLRLGARVIMGCRDRARAEEAAGQLRRELRQAAECGPEPGVSGVGELIVRELDLASLR
  SVRAFCQEMLQEEPRLDVLINNAGIFQCPYMKTEDGFEMQFGVNHLGHFLLTNLLLGLLK
  SSAPSRIVVVSSKLYKYGDINFDDLNSEQSYNKSFCYSRSKLANILFTRELARRLEGTNV
  TVNVLHPGIVRTNLGRHIHIPLLVKPLFNLVSWAFFKTPVEGAQTSIYLASSPEVEGVSG
  RYFGDCKEEELLPKAMDESVARKLWDISEVMVGLLK
• Function: Retinol dehydrogenase with a clear preference for NADP. Displays high activity towards 9-cis, 11-cis and all-trans-retinol. Shows a very weak activity towards 13-cis-retinol. Has no activity towards steroid.
• Tissue Specificity: Widely expressed.
• Reactome Pathway: RA biosynthesis pathway (R-HSA-5365859)

Molecular Interaction Atlas (MIA) of This DOT

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Retinol dehydrogenase 14 (RDH14).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Retinol dehydrogenase 14 (RDH14).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Retinol dehydrogenase 14 (RDH14).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Retinol dehydrogenase 14 (RDH14).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Retinol dehydrogenase 14 (RDH14).	[1]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Retinol dehydrogenase 14 (RDH14).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Retinol dehydrogenase 14 (RDH14).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Retinol dehydrogenase 14 (RDH14).	[6]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] 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.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [6] 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.
• [7] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.