Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFVI3EY)

• DOT Name: Overexpressed in colon carcinoma 1 protein (C12ORF75)
• Synonyms: OCC-1; AGD3
• Gene Name: C12ORF75
• Related Disease:
  Chronic renal failure
  Adult glioblastoma
  Carcinoma
  Colon carcinoma
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Ataxia-telangiectasia
  Clear cell adenocarcinoma
  Colorectal carcinoma
• UniProt ID: OCC1_HUMAN
• Pfam ID: PF15506
• Sequence:
  MGCGNSTATSAGAGQGPAGAAKDVTEESVTEDDKRRNYGGVYVGLPSEAVNMVSSQTKTV
  RKN
• Tissue Specificity: High expression in placenta, skeletal muscle, kidney and pancreas tissues. Absent or very faint expression in heart, brain, lung and liver. Expressed during adipogenic differentiation of mesenchymal stem cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[3]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[5]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[5]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[5]
Ataxia-telangiectasia	DISP3EVR	Limited	Genetic Variation	[5]
Clear cell adenocarcinoma	DISYUGHZ	Limited	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[8]

11 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 Overexpressed in colon carcinoma 1 protein (C12ORF75).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Overexpressed in colon carcinoma 1 protein (C12ORF75).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Overexpressed in colon carcinoma 1 protein (C12ORF75).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Overexpressed in colon carcinoma 1 protein (C12ORF75).	[12]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Overexpressed in colon carcinoma 1 protein (C12ORF75).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Overexpressed in colon carcinoma 1 protein (C12ORF75).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Overexpressed in colon carcinoma 1 protein (C12ORF75).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Overexpressed in colon carcinoma 1 protein (C12ORF75).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Overexpressed in colon carcinoma 1 protein (C12ORF75).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Overexpressed in colon carcinoma 1 protein (C12ORF75).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Overexpressed in colon carcinoma 1 protein (C12ORF75).	[18]

References

• [1] Genetics of Chronic Kidney Disease Stages Across Ancestries: The PAGE Study.Front Genet. 2019 May 24;10:494. doi: 10.3389/fgene.2019.00494. eCollection 2019.
• [2] Assessment of ApoC1, LuzP6, C12orf75 and OCC-1 in cystic glioblastoma using MALDI-TOF mass spectrometry, immunohistochemistry and qRT-PCR.Med Mol Morphol. 2019 Dec;52(4):217-225. doi: 10.1007/s00795-019-00223-8. Epub 2019 Apr 20.
• [3] Cloning of the mRNA of overexpression in colon carcinoma-1: a sequence overexpressed in a subset of colon carcinomas.Cancer Genet Cytogenet. 2002 Feb;133(1):55-60. doi: 10.1016/s0165-4608(01)00634-3.
• [4] Alternative splicing of the OCC-1 gene generates three splice variants and a novel exonic microRNA, which regulate the Wnt signaling pathway.RNA. 2017 Jan;23(1):70-85. doi: 10.1261/rna.056317.116. Epub 2016 Oct 21.
• [5] The oncogenic phosphatase PPM1D confers cisplatin resistance in ovarian carcinoma cells by attenuating checkpoint kinase 1 and p53 activation.Oncogene. 2012 Apr 26;31(17):2175-86. doi: 10.1038/onc.2011.399. Epub 2011 Sep 19.
• [6] Long noncoding RNA OCC-1 suppresses cell growth through destabilizing HuR protein in colorectal cancer.Nucleic Acids Res. 2018 Jun 20;46(11):5809-5821. doi: 10.1093/nar/gky214.
• [7] Establishment and characterization of a new human cell line derived from ovarian clear cell carcinoma.Gynecol Oncol. 1990 Jul;38(1):37-45. doi: 10.1016/0090-8258(90)90008-9.
• [8] Expression analysis of circulating plasma long noncoding RNAs in colorectal cancer: The relevance of lncRNAs ATB and CCAT1 as potential clinical hallmarks.J Cell Physiol. 2019 Dec;234(12):22028-22033. doi: 10.1002/jcp.28765. Epub 2019 May 15.
• [9] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [10] 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.
• [11] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [12] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [13] 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.
• [14] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [15] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [16] 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.
• [17] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [18] 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.