Details of Drug Off-Target (DOT)

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

• DOT Name: UPF0669 protein C6orf120 (C6ORF120)
• Gene Name: C6ORF120
• Related Disease:
  Acquired immune deficiency syndrome
  Autoimmune hepatitis
  Familial multiple trichoepithelioma
• UniProt ID: CF120_HUMAN
• Pfam ID: PF17065
• Sequence:
  MAAPRGRAAPWTTALLLLLASQVLSPGSCADEEEVPEEWVLLHVVQGQIGAGNYSYLRLN
  HEGKIVLRMRSLKGDADLYVSASSLHPSFDDYELQSATCGPDAVSIPAHFRRPVGIGVYG
  HPSHLESEFEMKVYYDGTVEQHPFGEAAYPADGADAGQKHAGAPEDASQEEESVLWTILI
  SILKLVLEILF
• Function: May be involved in induction of apoptosis in CD4(+) T-cells, but not CD8(+) T-cells or hepatocytes.
• Tissue Specificity: Mainly expressed in hepatocytes and some weak expression in germinal center cells of lymph nodes.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acquired immune deficiency syndrome	DISL5UOX	Strong	Biomarker	[1]
Autoimmune hepatitis	DISOX03Q	Strong	Biomarker	[2]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of UPF0669 protein C6orf120 (C6ORF120).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of UPF0669 protein C6orf120 (C6ORF120).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of UPF0669 protein C6orf120 (C6ORF120).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of UPF0669 protein C6orf120 (C6ORF120).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of UPF0669 protein C6orf120 (C6ORF120).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of UPF0669 protein C6orf120 (C6ORF120).	[10]

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 affects the methylation of UPF0669 protein C6orf120 (C6ORF120).	[9]

References

• [1] Role of C6ORF120, an N-glycosylated protein, is implicated in apoptosis of CD4?T lymphocytes.Chin Med J (Engl). 2011 Nov;124(21):3560-7.
• [2] Deletion of the C6orf120 gene with unknown function ameliorates autoimmune hepatitis induced by concanavalin A.Cell Immunol. 2018 Sep;331:9-15. doi: 10.1016/j.cellimm.2018.04.017. Epub 2018 May 2.
• [3] MicroRNA-17 is downregulated in esophageal adenocarcinoma cancer stem-like cells and promotes a radioresistant phenotype.Oncotarget. 2017 Feb 14;8(7):11400-11413. doi: 10.18632/oncotarget.13940.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [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.