Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCMT4L7)

• DOT Name: THAP domain-containing protein 10 (THAP10)
• Gene Name: THAP10
• Related Disease:
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
• UniProt ID: THA10_HUMAN
• Pfam ID: PF05485
• Sequence:
  MPARCVAAHCGNTTKSGKSLFRFPKDRAVRLLWDRFVRGCRADWYGGNDRSVICSDHFAP
  ACFDVSSVIQKNLRFSQRLRLVAGAVPTLHRVPAPAPKRGEEGDQAGRLDTRGELQAARH
  SEAAPGPVSCTRPRAGKQAAASQITCENELVQTQPHADNPSNTVTSVPTHCEEGPVHKST
  QISLKRPRHRSVGIQAKVKAFGKRLCNATTQTEELWSRTSSLFDIYSSDSETDTDWDIKS
  EQSDLSYMAVQVKEETC

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[2]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[2]
Breast neoplasm	DISNGJLM	Strong	Posttranslational Modification	[2]

8 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 THAP domain-containing protein 10 (THAP10).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of THAP domain-containing protein 10 (THAP10).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of THAP domain-containing protein 10 (THAP10).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of THAP domain-containing protein 10 (THAP10).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of THAP domain-containing protein 10 (THAP10).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of THAP domain-containing protein 10 (THAP10).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of THAP domain-containing protein 10 (THAP10).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of THAP domain-containing protein 10 (THAP10).	[10]

References

• [1] A novel epigenetic AML1-ETO/THAP10/miR-383 mini-circuitry contributes to t(8;21) leukaemogenesis.EMBO Mol Med. 2017 Jul;9(7):933-949. doi: 10.15252/emmm.201607180.
• [2] Silencing of LRRC49 and THAP10 genes by bidirectional promoter hypermethylation is a frequent event in breast cancer.Int J Oncol. 2008 Jul;33(1):25-31.
• [3] 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.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] 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.
• [6] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.