Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2MCLSE)

• DOT Name: UPF0729 protein C18orf32 (C18ORF32)
• Synonyms: Putative NF-kappa-B-activating protein 200
• Gene Name: C18ORF32
• Related Disease: Glycosylphosphatidylinositol biosynthesis defect 25
• UniProt ID: CR032_HUMAN
• Pfam ID: PF14975
• Sequence:
  MVCIPCIVIPVLLWIYKKFLEPYIYPLVSPFVSRIWPKKAIQESNDTNKGKVNFKGADMN
  GLPTKGPTEICDKKKD
• Function: May activate the NF-kappa-B signaling pathway.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glycosylphosphatidylinositol biosynthesis defect 25	DIS1Z19Q	Limited	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of UPF0729 protein C18orf32 (C18ORF32).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of UPF0729 protein C18orf32 (C18ORF32).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of UPF0729 protein C18orf32 (C18ORF32).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of UPF0729 protein C18orf32 (C18ORF32).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of UPF0729 protein C18orf32 (C18ORF32).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of UPF0729 protein C18orf32 (C18ORF32).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of UPF0729 protein C18orf32 (C18ORF32).	[9]

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 UPF0729 protein C18orf32 (C18ORF32).	[6]

References

• [1] C18orf32 loss-of-function is associated with a neurodevelopmental disorder with hypotonia and contractures. Hum Genet. 2022 Aug;141(8):1423-1429. doi: 10.1007/s00439-022-02433-0. Epub 2022 Feb 2.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] 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.
• [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] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.