Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZDNL65)

• DOT Name: Clarin-3 (CLRN3)
• Synonyms: Transmembrane protein 12; Usher syndrome type-3A-like protein 1
• Gene Name: CLRN3
• UniProt ID: CLRN3_HUMAN
• Sequence:
  MPTTKKTLMFLSSFFTSLGSFIVICSILGTQAWITSTIAVRDSASNGSIFITYGLFRGES
  SEELSHGLAEPKKKFAVLEILNNSSQKTLHSVTILFLVLSLITSLLSSGFTFYNSISNPY
  QTFLGPTGVYTWNGLGASFVFVTMILFVANTQSNQLSEELFQMLYPATTSKGTTHSYGYS
  FWLILLVILLNIVTVTIIIFYQKARYQRKQEQRKPMEYAPRDGILF

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Clarin-3 (CLRN3).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Clarin-3 (CLRN3).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Clarin-3 (CLRN3).	[1]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Clarin-3 (CLRN3).	[4]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Clarin-3 (CLRN3).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Clarin-3 (CLRN3).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Clarin-3 (CLRN3).	[7]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Clarin-3 (CLRN3).	[3]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Clarin-3 (CLRN3).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Clarin-3 (CLRN3).	[8]

References

• [1] 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.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [6] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] 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.