Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOJ1KUA)

• DOT Name: GTP-binding protein 2 (GTPBP2)
• Gene Name: GTPBP2
• Related Disease:
  Jaberi-Elahi syndrome
  Intellectual disability
  Xeroderma pigmentosum variant type
  Carcinoma
  Cholestasis
  Nervous system disease
  Neurodevelopmental disorder
• UniProt ID: GTPB2_HUMAN
• Pfam ID: PF00009
• Sequence:
  MDSRVSELFGGCCRPGGGPAVGGTLKARGAGSSSGCGGPKGKKKNGRNRGGKANNPPYLP
  PEAEDGNIEYKLKLVNPSQYRFEHLVTQMKWRLQEGRGEAVYQIGVEDNGLLVGLAEEEM
  RASLKTLHRMAEKVGADITVLREREVDYDSDMPRKITEVLVRKVPDNQQFLDLRVAVLGN
  VDSGKSTLLGVLTQGELDNGRGRARLNLFRHLHEIQSGRTSSISFEILGFNSKGEVVNYS
  DSRTAEEICESSSKMITFIDLAGHHKYLHTTIFGLTSYCPDCALLLVSANTGIAGTTREH
  LGLALALKVPFFIVVSKIDLCAKTTVERTVRQLERVLKQPGCHKVPMLVTSEDDAVTAAQ
  QFAQSPNVTPIFTLSSVSGESLDLLKVFLNILPPLTNSKEQEELMQQLTEFQVDEIYTVP
  EVGTVVGGTLSSGICREGDQLVVGPTDDGCFLELRVCSIQRNRSACRVLRAGQAATLALG
  DFDRALLRKGMVMVSPEMNPTICSVFEAEIVLLFHATTFRRGFQVTVHVGNVRQTAVVEK
  IHAKDKLRTGEKAVVRFRFLKHPEYLKVGAKLLFREGVTKGIGHVTDVQAITAGEAQANM
  GF
• Tissue Specificity: Predominantly expressed in thymus, spleen, and testis. Expressed at lower levels in brain, lung, kidney, and ovary.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Jaberi-Elahi syndrome	DIS1FFAU	Definitive	Autosomal recessive	[1]
Intellectual disability	DISMBNXP	Strong	Biomarker	[2]
Xeroderma pigmentosum variant type	DISNPX76	moderate	CausalMutation	[3]
Carcinoma	DISH9F1N	Limited	Biomarker	[4]
Cholestasis	DISDJJWE	Limited	Biomarker	[5]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[6]
Neurodevelopmental disorder	DIS372XH	Limited	Biomarker	[6]

19 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 GTP-binding protein 2 (GTPBP2).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of GTP-binding protein 2 (GTPBP2).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of GTP-binding protein 2 (GTPBP2).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GTP-binding protein 2 (GTPBP2).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of GTP-binding protein 2 (GTPBP2).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of GTP-binding protein 2 (GTPBP2).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of GTP-binding protein 2 (GTPBP2).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of GTP-binding protein 2 (GTPBP2).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of GTP-binding protein 2 (GTPBP2).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of GTP-binding protein 2 (GTPBP2).	[15]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of GTP-binding protein 2 (GTPBP2).	[16]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of GTP-binding protein 2 (GTPBP2).	[17]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of GTP-binding protein 2 (GTPBP2).	[18]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of GTP-binding protein 2 (GTPBP2).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of GTP-binding protein 2 (GTPBP2).	[20]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of GTP-binding protein 2 (GTPBP2).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of GTP-binding protein 2 (GTPBP2).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of GTP-binding protein 2 (GTPBP2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of GTP-binding protein 2 (GTPBP2).	[22]

References

• [1] Clinical delineation of GTPBP2-associated neuro-ectodermal syndrome: Report of two new families and review of the literature. Clin Genet. 2019 May;95(5):601-606. doi: 10.1111/cge.13523. Epub 2019 Mar 19.
• [2] RNA function. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration.Science. 2014 Jul 25;345(6195):455-9. doi: 10.1126/science.1249749.
• [3] Four types of possible founder mutations are responsible for 87% of Japanese patients with Xeroderma pigmentosum variant type.J Dermatol Sci. 2008 Nov;52(2):144-8. doi: 10.1016/j.jdermsci.2008.07.001. Epub 2008 Aug 13.
• [4] High-resolution genomic analysis does not qualify atypical plexus papilloma as a separate entity among choroid plexus tumors.J Neuropathol Exp Neurol. 2015 Feb;74(2):110-20. doi: 10.1097/NEN.0000000000000154.
• [5] 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.
• [6] Biallelic inactivating variants in the GTPBP2 gene cause a neurodevelopmental disorder with severe intellectual disability.Eur J Hum Genet. 2018 Apr;26(4):592-598. doi: 10.1038/s41431-018-0097-3. Epub 2018 Feb 15.
• [7] 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.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [10] 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.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [13] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [14] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [15] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [16] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [17] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [18] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [19] Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell lines. J Pharm Pharmacol. 2005 Jan;57(1):83-92.
• [20] 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.
• [21] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.