Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNUV6MQ)

• DOT Name: BTB/POZ domain-containing protein 7 (BTBD7)
• Gene Name: BTBD7
• Related Disease:
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Colorectal carcinoma
  Hepatocellular carcinoma
  Liver cancer
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
• UniProt ID: BTBD7_HUMAN
• Pfam ID: PF07707 ; PF00651
• Sequence:
  MGANASNYPHSCSPRVGGNSQAQQTFIGTSSYSQQGYGCESKLYSLDHGHEKPQDKKKRT
  SGLATLKKKFIKRRKSNRSADHAKQMRELLSGWDVRDVNALVEEYEGTSALKELSLQASL
  ARPEARTLQKDMADLYEYKYCTDVDLIFQETCFPVHRAILAARCPFFKTLLSSSPEYGAE
  IIMDINTAGIDMPMFSALLHYLYTGEFGMEDSRFQNVDILVQLSEEFGTPNSLDVDMRGL
  FDYMCYYDVVLSFSSDSELVEAFGGNQNCLDEELKAHKAVISARSPFFRNLLQRRIRTGE
  EITDRTLRTPTRIILDESIIPKKYATVILHCMYTDVVDLSVLHCSPSVGSLSEVQALVAG
  KPNMTRAEEAMELYHIALFLEFNMLAQGCEDIIAESISLDTLIAILKWSSHPYGSKWVHR
  QALHFLCEEFSQVMTSDVFYELSKDHLLTAIQSDYLQASEQDILKYLIKWGEHQLMKRIA
  DREPNLLSGTAHSVNKRGVKRRDLDMEELREILSSLLPFVRIEHILPINSEVLSDAMKRG
  LISTPPSDMLPTTEGGKSNAWLRQKNAGIYVRPRLFSPYVEEAKSVLDEMMVEQTDLVRL
  RMVRMSNVPDTLYMVNNAVPQCCHMISHQQISSNQSSPPSVVANEIPVPRLLIMKDMVRR
  LQELRHTEQVQRAYALNCGEGATVSYEIQIRVLREFGLADAAAELLQNPHKFFPDERFGD
  ESPLLTMRQPGRCRVNSTPPAETMFTDLDSFVAFHPPLPPPPPPYHPPATPIHNQLKAGW
  KQRPPSQHPSRSFSYPCNHSLFHSRTAPKAGPPPVYLPSVKAAPPDCTSTAGLGRQTVAA
  AAATTTSTATAAAAAASEKQVRTQPVLNDLMPDIAVGVSTLSLKDRRLPELAVDTELSQS
  VSEAGPGPPQHLSCIPQRHTHTSRKKHTLEQKTDTRENPQEYPDFYDFSNAACRPSTPAL
  SRRTPSPSQGGYFGPDLYSHNKASPSGLKSAYLPGQTSPKKQEEARREYPLSPDGHLHRQ
  KNEPIHLDVVEQPPQRSDFPLAAPENASTGPAHVRGRTAVETDLTFGLTPNRPSLSACSS
  EAPEERSGRRLADSESLGHGAQRNTDLEREDSISRGRRSPSKPDFLYKKSAL
• Function: Acts as a mediator of epithelial dynamics and organ branching by promoting cleft progression. Induced following accumulation of fibronectin in forming clefts, leading to local expression of the cell-scattering SNAIL2 and suppression of E-cadherin levels, thereby altering cell morphology and reducing cell-cell adhesion. This stimulates cell separation at the base of forming clefts by local, dynamic intercellular gap formation and promotes cleft progression.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Liver cancer	DISDE4BI	Strong	Genetic Variation	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]

3 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 BTB/POZ domain-containing protein 7 (BTBD7).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of BTB/POZ domain-containing protein 7 (BTBD7).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of BTB/POZ domain-containing protein 7 (BTBD7).	[10]

6 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 7 (BTBD7).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of BTB/POZ domain-containing protein 7 (BTBD7).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of BTB/POZ domain-containing protein 7 (BTBD7).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of BTB/POZ domain-containing protein 7 (BTBD7).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of BTB/POZ domain-containing protein 7 (BTBD7).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of BTB/POZ domain-containing protein 7 (BTBD7).	[7]

References

• [1] Silencing of Btbd7 Inhibited Epithelial-Mesenchymal Transition and Chemoresistance in CD133(+) Lung Carcinoma A549 Cells.Oncol Res. 2017 May 24;25(5):819-829. doi: 10.3727/096504016X14772349843854. Epub 2016 Oct 26.
• [2] Sleeping beauty genetic screen identifies miR-23b::BTBD7 gene interaction as crucial for colorectal cancer metastasis.EBioMedicine. 2019 Aug;46:79-93. doi: 10.1016/j.ebiom.2019.06.044. Epub 2019 Jul 11.
• [3] FUP1, a gene associated with hepatocellular carcinoma, stimulates NIH3T3 cell proliferation and tumor formation in nude mice.Biochem Biophys Res Commun. 2001 Sep 7;286(5):1033-8. doi: 10.1006/bbrc.2001.5478.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [8] 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.
• [9] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [10] 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.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.