Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT07ANSG)

• DOT Name: RING finger protein 141 (RNF141)
• Synonyms: Zinc finger protein 230
• Gene Name: RNF141
• Related Disease:
  Barrett esophagus
  Familial multiple trichoepithelioma
• UniProt ID: RN141_HUMAN
• PDB ID: 2ECN; 5XEK
• Pfam ID: PF13639
• Sequence:
  MGQQISDQTQLVINKLPEKVAKHVTLVRESGSLTYEEFLGRVAELNDVTAKVASGQEKHL
  LFEVQPGSDSSAFWKVVVRVVCTKINKSSGIVEASRIMNLYQFIQLYKDITSQAAGVLAQ
  SSTSEEPDENSSSVTSCQASLWMGRVKQLTDEEECCICMDGRADLILPCAHSFCQKCIDK
  WSDRHRNCPICRLQMTGANESWVVSDAPTEDDMANYILNMADEAGQPHRP
• Function: May be involved in spermatogenesis.
• Tissue Specificity: Isoform 1 is testis-specific. Isoform 2 is expressed in heart, brain, skeletal muscle, kidney and pancreas. Isoform 1 is not expressed in fetus or in azoospermic patients.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Barrett esophagus	DIS416Y7	Strong	Altered Expression	[1]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of RING finger protein 141 (RNF141).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RING finger protein 141 (RNF141).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RING finger protein 141 (RNF141).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of RING finger protein 141 (RNF141).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of RING finger protein 141 (RNF141).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of RING finger protein 141 (RNF141).	[7]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of RING finger protein 141 (RNF141).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of RING finger protein 141 (RNF141).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of RING finger protein 141 (RNF141).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of RING finger protein 141 (RNF141).	[7]

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 RING finger protein 141 (RNF141).	[10]

References

• [1] RING finger proteins are involved in the progression of barrett esophagus to esophageal adenocarcinoma: a preliminary study.Gut Liver. 2014 Sep;8(5):487-94. doi: 10.5009/gnl13133. Epub 2014 Feb 24.
• [2] 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.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] 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.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [9] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.