Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9TPYNM)

• DOT Name: Zinc finger and BTB domain-containing protein 24
• Synonyms: Zinc finger protein 450
• Gene Name: ZBTB24
• Related Disease:
  Immunodeficiency-centromeric instability-facial anomalies syndrome 2
  Immunodeficiency-centromeric instability-facial anomalies syndrome
• UniProt ID: ZBT24_HUMAN
• Pfam ID: PF00651 ; PF00096
• Sequence:
  MAETSPEPSGQLVVHSDAHSDTVLASFEDQRKKGFLCDITLIVENVHFRAHKALLAASSE
  YFSMMFAEEGEIGQSIYMLEGMVADTFGILLEFIYTGYLHASEKSTEQILATAQFLKVYD
  LVKAYTDFQNNHSSPKPTTLNTAGAPVVVISNKKNDPPKRKRGRPKKVNTLQEEKSELAA
  EEEIQLRVNNSVQNRQNFVVKGDSGVLNEQIAAKEKEESEPTCEPSREEEMPVEKDENYD
  PKTEDGQASQSRYSKRRIWRSVKLKDYKLVGDQEDHGSAKRICGRRKRPGGPEARCKDCG
  KVFKYNHFLAIHQRSHTGERPFKCNECGKGFAQKHSLQVHTRMHTGERPYTCTVCSKALT
  TKHSLLEHMSLHSGQKSFTCDQCGKYFSQNRQLKSHYRVHTGHSLPECKDCHRKFMDVSQ
  LKKHLRTHTGEKPFTCEICGKSFTAKSSLQTHIRIHRGEKPYSCGICGKSFSDSSAKRRH
  CILHTGKKPFSCPECNLQFARLDNLKAHLKIHSKEKHASDASSISGSSNTEEVRNILQLQ
  PYQLSTSGEQEIQLLVTDSVHNINFMPGPSQGISIVTAESSQNMTADQAANLTLLTQQPE
  QLQNLILSAQQEQTEHIQSLNMIESQMGPSQTEPVHVITLSKETLEHLHAHQEQTEELHL
  ATSTSDPAQHLQLTQEPGPPPPTHHVPQPTPLGQEQS
• Function: May be involved in BMP2-induced transcription.
• Tissue Specificity: Widely expressed, with highest levels in naive B-cells.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency-centromeric instability-facial anomalies syndrome 2	DIS66SXL	Strong	Autosomal recessive	[1]
Immunodeficiency-centromeric instability-facial anomalies syndrome	DISQ0KIE	Supportive	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Zinc finger and BTB domain-containing protein 24.	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Zinc finger and BTB domain-containing protein 24.	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Zinc finger and BTB domain-containing protein 24.	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Zinc finger and BTB domain-containing protein 24.	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Zinc finger and BTB domain-containing protein 24.	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Zinc finger and BTB domain-containing protein 24.	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Zinc finger and BTB domain-containing protein 24.	[8]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Zinc finger and BTB domain-containing protein 24.	[6]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Zinc finger and BTB domain-containing protein 24.	[6]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Zinc finger and BTB domain-containing protein 24.	[6]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Zinc finger and BTB domain-containing protein 24.	[6]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Zinc finger and BTB domain-containing protein 24.	[6]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Zinc finger and BTB domain-containing protein 24.	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Zinc finger and BTB domain-containing protein 24.	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Zinc finger and BTB domain-containing protein 24.	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Zinc finger and BTB domain-containing protein 24.	[13]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Zinc finger and BTB domain-containing protein 24.	[14]

References

• [1] Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. Am J Hum Genet. 2011 Jun 10;88(6):796-804. doi: 10.1016/j.ajhg.2011.04.018. Epub 2011 May 19.
• [2] A novel deletion in ZBTB24 in a Lebanese family with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. Clin Genet. 2012 Nov;82(5):489-93. doi: 10.1111/j.1399-0004.2011.01783.x. Epub 2011 Oct 5.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [10] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] 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.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [14] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.