Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAZ4DWD)

• DOT Name: BTB/POZ domain-containing protein 2 (BTBD2)
• Gene Name: BTBD2
• Related Disease: Glioblastoma multiforme
• UniProt ID: BTBD2_HUMAN
• PDB ID: 3NO8
• Pfam ID: PF07707 ; PF00651 ; PF08005
• Sequence:
  MAAGGSGGRASCPPGVGVGPGTGGSPGPSANAAATPAPGNAAAAAAAAAAAAAAPGPTPP
  APPGPGTDAQAAGAERAEEAAGPGAAALQREAAYNWQASKPTVQERFAFLFNNEVLCDVH
  FLVGKGLSSQRIPAHRFVLAVGSAVFDAMFNGGMATTSTEIELPDVEPAAFLALLKFLYS
  DEVQIGPETVMTTLYTAKKYAVPALEAHCVEFLKKNLRADNAFMLLTQARLFDEPQLASL
  CLENIDKNTADAITAEGFTDIDLDTLVAVLERDTLGIREVRLFNAVVRWSEAECQRQQLQ
  VTPENRRKVLGKALGLIRFPLMTIEEFAAGPAQSGILVDREVVSLFLHFTVNPKPRVEFI
  DRPRCCLRGKECSINRFQQVESRWGYSGTSDRIRFSVNKRIFVVGFGLYGSIHGPTDYQV
  NIQIIHTDSNTVLGQNDTGFSCDGSASTFRVMFKEPVEVLPNVNYTACATLKGPDSHYGT
  KGLRKVTHESPTTGAKTCFTFCYAAGNNNGTSVEDGQIPEVIFYT

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of BTB/POZ domain-containing protein 2 (BTBD2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of BTB/POZ domain-containing protein 2 (BTBD2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of BTB/POZ domain-containing protein 2 (BTBD2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of BTB/POZ domain-containing protein 2 (BTBD2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of BTB/POZ domain-containing protein 2 (BTBD2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of BTB/POZ domain-containing protein 2 (BTBD2).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of BTB/POZ domain-containing protein 2 (BTBD2).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of BTB/POZ domain-containing protein 2 (BTBD2).	[7]

References

• [1] Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict glioblastoma survival.J Clin Oncol. 2010 May 10;28(14):2467-74. doi: 10.1200/JCO.2009.26.6213. Epub 2010 Apr 5.
• [2] 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.
• [3] 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.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] 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.
• [6] Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo. Br J Haematol. 2005 Mar;128(5):636-44.
• [7] 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.
• [8] 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.
• [9] 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.