Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7AVTFB)

• DOT Name: Uncharacterized protein KIAA0513 (KIAA0513)
• Gene Name: KIAA0513
• Related Disease:
  Amyotrophic lateral sclerosis
  Schizophrenia
  Acute myelogenous leukaemia
  Advanced cancer
  Neoplasm
• UniProt ID: K0513_HUMAN
• Sequence:
  METPEVPVGSLIDFGPEAPTSSPLEAPPPVLQDGDGSLGDGASESETTESADSENDMGES
  PSHPSWDQDRRSSSNESFSSNQSTESTQDEETLALRDFMRGYVEKIFSGGEDLDQEEKAK
  FGEYCSSENGKGREWFARYVSAQRCNSKCVSEATFYRLVQSFAVVLFECHQMDDFGPAKN
  LMTMCFTYYHIGKPQLLPPESREKPAGSIDSYLKSANSWLAEKKDIAERLLKNTSARTEN
  VKGFFGGLETKLKGPLARRNEEDENKPQEKRPRAVTAYSPEDEKKGEKIYLYTHLKQQPI
  WHTLRFWNAAFFDAVHCERTKRSPTTRGDAGEEEEKREKWCHMTQEERDDSLRFNENITF
  GQLGTFTHNMLAFGLNKKLCNDFLKKQAVIGNLDEEQYKLLSDHIEQMATE
• Tissue Specificity: Widely expressed, highest levels in cerebellum, brain cortex, hippocampus, pons, putamen and amygdala. Highly expressed in neurons, but also present in glial cells. Slightly higher expression in the dorsolateral prefrontal cortex of schizophrenic patients compared to control individuals.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[1]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]
Neoplasm	DISZKGEW	Limited	Biomarker	[4]

19 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 KIAA0513 (KIAA0513).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[12]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[13]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[14]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[15]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[18]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Uncharacterized protein KIAA0513 (KIAA0513).	[23]

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 decreases the methylation of Uncharacterized protein KIAA0513 (KIAA0513).	[17]

References

• [1] Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.Neurobiol Aging. 2013 Jan;34(1):357.e7-19. doi: 10.1016/j.neurobiolaging.2012.07.017. Epub 2012 Sep 5.
• [2] Characterization of KIAA0513, a novel signaling molecule that interacts with modulators of neuroplasticity, apoptosis, and the cytoskeleton.Brain Res. 2006 Nov 22;1121(1):1-11. doi: 10.1016/j.brainres.2006.08.099. Epub 2006 Sep 29.
• [3] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [4] Comprehensive Analysis of Genome Rearrangements in Eight Human Malignant Tumor Tissues.PLoS One. 2016 Jul 8;11(7):e0158995. doi: 10.1371/journal.pone.0158995. eCollection 2016.
• [5] 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.
• [6] 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.
• [7] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [12] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [15] 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.
• [16] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [17] 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.
• [18] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [19] 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.
• [20] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [23] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.