Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3O3FC3)

• DOT Name: UPF0462 protein C4orf33 (C4ORF33)
• Gene Name: C4ORF33
• Related Disease: Major depressive disorder
• UniProt ID: CD033_HUMAN
• Sequence:
  MDFKIEHTWDGFPVKHEPVFIRLNPGDRGVMMDISAPFFRDPPAPLGEPGKPFNELWDYE
  VVEAFFLNDITEQYLEVELCPHGQHLVLLLSGRRNVWKQELPLSFRMSRGETKWEGKAYL
  PWSYFPPNVTKFNSFAIHGSKDKRSYEALYPVPQHELQQGQKPDFHCLEYFKSFNFNTLL
  GEEWKQPESDLWLIEKCDI

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of UPF0462 protein C4orf33 (C4ORF33).	[2]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of UPF0462 protein C4orf33 (C4ORF33).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of UPF0462 protein C4orf33 (C4ORF33).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of UPF0462 protein C4orf33 (C4ORF33).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of UPF0462 protein C4orf33 (C4ORF33).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of UPF0462 protein C4orf33 (C4ORF33).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of UPF0462 protein C4orf33 (C4ORF33).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of UPF0462 protein C4orf33 (C4ORF33).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of UPF0462 protein C4orf33 (C4ORF33).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of UPF0462 protein C4orf33 (C4ORF33).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of UPF0462 protein C4orf33 (C4ORF33).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of UPF0462 protein C4orf33 (C4ORF33).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of UPF0462 protein C4orf33 (C4ORF33).	[11]

References

• [1] Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder.Front Psychiatry. 2018 Mar 6;9:65. doi: 10.3389/fpsyt.2018.00065. eCollection 2018.
• [2] 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.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.