Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXL7SLI)

• DOT Name: Renal cancer differentiation gene 1 protein (C4ORF46)
• Gene Name: C4ORF46
• Related Disease:
  Clear cell renal carcinoma
  Kidney cancer
  Renal carcinoma
  Renal cell carcinoma
• UniProt ID: CD046_HUMAN
• Pfam ID: PF15725
• Sequence:
  MADPEELQVSSPPPPPPSSPSSSDASAASSPGGPVSLGWPVPSRSSGPTVDQLEEVELQI
  GDAAFSLTKLLEATSAVSAQVEELAFKCTENARFLKTWRDLLKEGYDSLKPDD
• Tissue Specificity: Expressed in the kidney, in epithelial cells in both proximal tubules and distal convoluted tubules.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	Strong	Posttranslational Modification	[1]
Kidney cancer	DISBIPKM	Strong	Biomarker	[1]
Renal carcinoma	DISER9XT	Strong	Biomarker	[1]
Renal cell carcinoma	DISQZ2X8	Strong	Posttranslational Modification	[1]

14 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 Renal cancer differentiation gene 1 protein (C4ORF46).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[8]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[9]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[7]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Renal cancer differentiation gene 1 protein (C4ORF46).	[9]

References

• [1] Expression and clinical significance of RCDG1 in renal cell carcinoma: a novel renal cancerassociated gene.Mol Med Rep. 2014 Sep;10(3):1583-9. doi: 10.3892/mmr.2014.2388. Epub 2014 Jul 16.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [10] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [11] 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.
• [12] 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.