Details of Drug Off-Target (DOT)

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

• DOT Name: Zinc finger and BTB domain-containing protein 20
• Synonyms: Dendritic-derived BTB/POZ zinc finger protein; Zinc finger protein 288
• Gene Name: ZBTB20
• Related Disease:
  Primrose syndrome
  Type-1/2 diabetes
• UniProt ID: ZBT20_HUMAN
• Pfam ID: PF00651 ; PF00096
• Sequence:
  MLERKKPKTAENQKASEENEITQPGGSSAKPGLPCLNFEAVLSPDPALIHSTHSLTNSHA
  HTGSSDCDISCKGMTERIHSINLHNFSNSVLETLNEQRNRGHFCDVTVRIHGSMLRAHRC
  VLAAGSPFFQDKLLLGYSDIEIPSVVSVQSVQKLIDFMYSGVLRVSQSEALQILTAASIL
  QIKTVIDECTRIVSQNVGDVFPGIQDSGQDTPRGTPESGTSGQSSDTESGYLQSHPQHSV
  DRIYSALYACSMQNGSGERSFYSGAVVSHHETALGLPRDHHMEDPSWITRIHERSQQMER
  YLSTTPETTHCRKQPRPVRIQTLVGNIHIKQEMEDDYDYYGQQRVQILERNESEECTEDT
  DQAEGTESEPKGESFDSGVSSSIGTEPDSVEQQFGPGAARDSQAEPTQPEQAAEAPAEGG
  PQTNQLETGASSPERSNEVEMDSTVITVSNSSDKSVLQQPSVNTSIGQPLPSTQLYLRQT
  ETLTSNLRMPLTLTSNTQVIGTAGNTYLPALFTTQPAGSGPKPFLFSLPQPLAGQQTQFV
  TVSQPGLSTFTAQLPAPQPLASSAGHSTASGQGEKKPYECTLCNKTFTAKQNYVKHMFVH
  TGEKPHQCSICWRSFSLKDYLIKHMVTHTGVRAYQCSICNKRFTQKSSLNVHMRLHRGEK
  SYECYICKKKFSHKTLLERHVALHSASNGTPPAGTPPGARAGPPGVVACTEGTTYVCSVC
  PAKFDQIEQFNDHMRMHVSDG
• Function: May be a transcription factor that may be involved in hematopoiesis, oncogenesis, and immune responses. Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal.
• Tissue Specificity: Expressed in spleen, lymph node, thymus, peripheral blood leukocytes, and fetal liver.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primrose syndrome	DISCS135	Definitive	Autosomal dominant	[1]
Type-1/2 diabetes	DISIUHAP	Strong	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Daunorubicin	DMQUSBT	Approved	Zinc finger and BTB domain-containing protein 20 affects the response to substance of Daunorubicin.	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Zinc finger and BTB domain-containing protein 20.	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Zinc finger and BTB domain-containing protein 20.	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Zinc finger and BTB domain-containing protein 20.	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Zinc finger and BTB domain-containing protein 20.	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Zinc finger and BTB domain-containing protein 20.	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Zinc finger and BTB domain-containing protein 20.	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Zinc finger and BTB domain-containing protein 20.	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of Zinc finger and BTB domain-containing protein 20.	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Zinc finger and BTB domain-containing protein 20.	[12]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Zinc finger and BTB domain-containing protein 20.	[13]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Zinc finger and BTB domain-containing protein 20.	[14]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Zinc finger and BTB domain-containing protein 20.	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Zinc finger and BTB domain-containing protein 20.	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Zinc finger and BTB domain-containing protein 20.	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Zinc finger and BTB domain-containing protein 20.	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Zinc finger and BTB domain-containing protein 20.	[21]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Zinc finger and BTB domain-containing protein 20.	[23]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Zinc finger and BTB domain-containing protein 20.	[24]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Zinc finger and BTB domain-containing protein 20.	[25]

4 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 Zinc finger and BTB domain-containing protein 20.	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Zinc finger and BTB domain-containing protein 20.	[18]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Zinc finger and BTB domain-containing protein 20.	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Zinc finger and BTB domain-containing protein 20.	[22]

References

• [1] Mutations in ZBTB20 cause Primrose syndrome. Nat Genet. 2014 Aug;46(8):815-7. doi: 10.1038/ng.3035. Epub 2014 Jul 13.
• [2] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [12] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [13] 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.
• [14] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [15] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [20] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [21] 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.
• [22] 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.
• [23] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [24] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [25] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.
• [26] Mapping genes that contribute to daunorubicin-induced cytotoxicity. Cancer Res. 2007 Jun 1;67(11):5425-33. doi: 10.1158/0008-5472.CAN-06-4431.