Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIIU4DI)

• DOT Name: UPF0538 protein C2orf76 (C2ORF76)
• Gene Name: C2ORF76
• Related Disease: Acute myelogenous leukaemia
• UniProt ID: CB076_HUMAN
• Pfam ID: PF10209
• Sequence:
  MAPGEVTITVRLIRSFEHRNFKPVVYHGVNLDQTVKEFIVFLKQDIPLRTNLPPPFRNYK
  YDALKIIHQAHKSKTNELVLSLEDDERLLLKEDSTLKAAGIASETEIAFFCEEDYKNYKA
  NPISSW

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[1]

2 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 UPF0538 protein C2orf76 (C2ORF76).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of UPF0538 protein C2orf76 (C2ORF76).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of UPF0538 protein C2orf76 (C2ORF76).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of UPF0538 protein C2orf76 (C2ORF76).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of UPF0538 protein C2orf76 (C2ORF76).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of UPF0538 protein C2orf76 (C2ORF76).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of UPF0538 protein C2orf76 (C2ORF76).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of UPF0538 protein C2orf76 (C2ORF76).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of UPF0538 protein C2orf76 (C2ORF76).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of UPF0538 protein C2orf76 (C2ORF76).	[11]

References

• [1] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] 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.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.