Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1GVN5H)

• DOT Name: TBC1 domain family member 2B (TBC1D2B)
• Gene Name: TBC1D2B
• Related Disease:
  Advanced cancer
  Neurodevelopmental disorder with seizures and gingival overgrowth
  Schizophrenia
• UniProt ID: TBD2B_HUMAN
• Pfam ID: PF00169 ; PF00566
• Sequence:
  MPGAGARAEEGGGGGEGAAQGAAAEPGAGPAREPARLCGYLQKLSGKGPLRGYRSRWFVF
  DARRCYLYYFKSPQDALPLGHLDIADACFSYQGPDEAAEPGTEPPAHFQVHSAGAVTVLK
  APNRQLMTYWLQELQQKRWEYCNSLDMVKWDSRTSPTPGDFPKGLVARDNTDLIYPHPNA
  SAEKARNVLAVETVPGELVGEQAANQPAPGHPNSINFYSLKQWGNELKNSMSSFRPGRGH
  NDSRRTVFYTNEEWELLDPTPKDLEESIVQEEKKKLTPEGNKGVTGSGFPFDFGRNPYKG
  KRPLKDIIGSYKNRHSSGDPSSEGTSGSGSVSIRKPASEMQLQVQSQQEELEQLKKDLSS
  QKELVRLLQQTVRSSQYDKYFTSSRLCEGVPKDTLELLHQKDDQILGLTSQLERFSLEKE
  SLQQEVRTLKSKVGELNEQLGMLMETIQAKDEVIIKLSEGEGNGPPPTVAPSSPSVVPVA
  RDQLELDRLKDNLQGYKTQNKFLNKEILELSALRRNAERRERDLMAKYSSLEAKLCQIES
  KYLILLQEMKTPVCSEDQGPTREVIAQLLEDALQVESQEQPEQAFVKPHLVSEYDIYGFR
  TVPEDDEEEKLVAKVRALDLKTLYLTENQEVSTGVKWENYFASTVNREMMCSPELKNLIR
  AGIPHEHRSKVWKWCVDRHTRKFKDNTEPGHFQTLLQKALEKQNPASKQIELDLLRTLPN
  NKHYSCPTSEGIQKLRNVLLAFSWRNPDIGYCQGLNRLVAVALLYLEQEDAFWCLVTIVE
  VFMPRDYYTKTLLGSQVDQRVFRDLMSEKLPRLHGHFEQYKVDYTLITFNWFLVVFVDSV
  VSDILFKIWDSFLYEGPKVIFRFALALFKYKEEEILKLQDSMSIFKYLRYFTRTILDARK
  LISISFGDLNPFPLRQIRNRRAYHLEKVRLELTELEAIREDFLRERDTSPDKGELVSDEE
  EDT
• Function: GTPase-activating protein that plays a role in the early steps of endocytosis.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Neurodevelopmental disorder with seizures and gingival overgrowth	DISCUKM0	Strong	Autosomal recessive	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]

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 TBC1 domain family member 2B (TBC1D2B).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of TBC1 domain family member 2B (TBC1D2B).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of TBC1 domain family member 2B (TBC1D2B).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of TBC1 domain family member 2B (TBC1D2B).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of TBC1 domain family member 2B (TBC1D2B).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of TBC1 domain family member 2B (TBC1D2B).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of TBC1 domain family member 2B (TBC1D2B).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of TBC1 domain family member 2B (TBC1D2B).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of TBC1 domain family member 2B (TBC1D2B).	[12]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of TBC1 domain family member 2B (TBC1D2B).	[13]

References

• [1] ZEB1/NuRD complex suppresses TBC1D2b to stimulate E-cadherin internalization and promote metastasis in lung cancer.Nat Commun. 2019 Nov 12;10(1):5125. doi: 10.1038/s41467-019-12832-z.
• [2] The contribution of de novo coding mutations to autism spectrum disorder. Nature. 2014 Nov 13;515(7526):216-21. doi: 10.1038/nature13908. Epub 2014 Oct 29.
• [3] Genome-wide association study identifies five new schizophrenia loci.Nat Genet. 2011 Sep 18;43(10):969-76. doi: 10.1038/ng.940.
• [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] 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.
• [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] 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.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] 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.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [13] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.