Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT27EBY3)

• DOT Name: Uncharacterized protein KIAA0040 (KIAA0040)
• Gene Name: KIAA0040
• Related Disease:
  Amyotrophic lateral sclerosis
  Alcohol dependence
• UniProt ID: K0040_HUMAN
• Sequence:
  MERISAFFSSIWDTILTKHQEGIYNTICLGVLLGLPLLVIITLLFICCHCCWSPPGKRGQ
  QPEKNKKKKKKKKKKDEEDLWISAQPKLLQMEKRPSLPV

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[1]
Alcohol dependence	DIS4ZSCO	moderate	Biomarker	[2]

17 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 Uncharacterized protein KIAA0040 (KIAA0040).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[11]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[12]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[16]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Uncharacterized protein KIAA0040 (KIAA0040).	[17]

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 Uncharacterized protein KIAA0040 (KIAA0040).	[14]

References

• [1] Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data.Lancet Neurol. 2007 Apr;6(4):322-8. doi: 10.1016/S1474-4422(07)70037-6.
• [2] Genome-wide association discoveries of alcohol dependence.Am J Addict. 2014 Nov-Dec;23(6):526-39. doi: 10.1111/j.1521-0391.2014.12147.x.
• [3] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [4] 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.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [13] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [14] 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.
• [15] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [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] 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.