Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCJ915F)

• DOT Name: Retinol dehydrogenase 16 (RDH16)
• Synonyms: EC 1.1.1.105; EC 1.1.1.209; EC 1.1.1.315; EC 1.1.1.53; Human epidermal retinol dehydrogenase; hRDH-E; Microsomal NAD(+)-dependent retinol dehydrogenase 4; RoDH-4; Short chain dehydrogenase/reductase family 9C member 8; Sterol/retinol dehydrogenase
• Gene Name: RDH16
• Related Disease:
  Hepatocellular carcinoma
  Malignant glioma
  Neoplasm
  Endometrium neoplasm
• UniProt ID: RDH16_HUMAN
• EC Number: 1.1.1.105; 1.1.1.209; 1.1.1.315; 1.1.1.53
• Pfam ID: PF00106
• Sequence:
  MWLYLAVFVGLYYLLHWYRERQVLSHLRDKYVFITGCDSGFGKLLARQLDARGLRVLAAC
  LTEKGAEQLRGQTSDRLETVTLDVTKTESVAAAAQWVKECVRDKGLWGLVNNAGISLPTA
  PNELLTKQDFVTILDVNLLGVIDVTLSLLPLVRRARGRVVNVSSVMGRVSLFGGGYCISK
  YGVEAFSDSLRRELSYFGVKVAMIEPGYFKTAVTSKERFLKSFLEIWDRSSPEVKEAYGE
  KFVADYKKSAEQMEQKCTQDLSLVTNCMEHALIACHPRTRYSAGWDAKLLYLPMSYMPTF
  LVDAIMYWVSPSPAKAL
• Function: Oxidoreductase with a preference for NAD. Oxidizes all-trans-retinol, 9-cis-retinol, 11-cis-retinol and 13-cis-retinol to the corresponding aldehydes. Has higher activity towards CRBP-bound retinol than with free retinol. Oxidizes also 3-alpha-hydroxysteroids. Oxidizes androstanediol and androsterone to dihydrotestosterone and androstanedione. Can also catalyze the reverse reaction.
• Tissue Specificity: Highly expressed in adult liver (at protein level) . Detected in endometrium, liver and foreskin . Detected in the spineous layers of adult skin, and at lower levels in basal and granular skin layers . Detected in fetal liver and lung.
• KEGG Pathway:
  Retinol metabolism (hsa00830)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  RA biosynthesis pathway (R-HSA-5365859)
  The canonical retinoid cycle in rods (twilight vision) (R-HSA-2453902)
• BioCyc Pathway: MetaCyc:ENSG00000139547-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Malignant glioma	DISFXKOV	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Endometrium neoplasm	DIS6OS2L	Limited	Biomarker	[3]

5 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 Retinol dehydrogenase 16 (RDH16).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Retinol dehydrogenase 16 (RDH16).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Retinol dehydrogenase 16 (RDH16).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Retinol dehydrogenase 16 (RDH16).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Retinol dehydrogenase 16 (RDH16).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Retinol dehydrogenase 16 (RDH16).	[7]

References

• [1] Clinical significance and function of RDH16 as a tumor-suppressing gene in hepatocellular carcinoma.Hepatol Res. 2020 Jan;50(1):110-120. doi: 10.1111/hepr.13432. Epub 2019 Dec 8.
• [2] NSPc1 promotes cancer stem cell self-renewal by repressing the synthesis of all-trans retinoic acid via targeting RDH16 in malignant glioma.Oncogene. 2017 Aug 17;36(33):4706-4718. doi: 10.1038/onc.2017.34. Epub 2017 Apr 10.
• [3] Expression of a retinol dehydrogenase (hRoDH-4), a member of the retinol/steroid dehydrogenase family implicated in retinoic acid biosynthesis, in normal and neoplastic endometria.Am J Obstet Gynecol. 2002 Apr;186(4):675-83. doi: 10.1067/mob.2002.122127.
• [4] 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.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.