Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ4584O)

• DOT Name: GPN-loop GTPase 3 (GPN3)
• Synonyms: ATP-binding domain 1 family member C
• Gene Name: GPN3
• Related Disease:
  Advanced cancer
  Trigeminal neuralgia
  Breast cancer
  Breast carcinoma
  Her2-receptor negative breast cancer
  HER2/NEU overexpressing breast cancer
• UniProt ID: GPN3_HUMAN
• Pfam ID: PF03029
• Sequence:
  MPRYAQLVMGPAGSGKSTYCATMVQHCEALNRSVQVVNLDPAAEHFNYSVMADIRELIEV
  DDVMEDDSLRFGPNGGLVFCMEYFANNFDWLENCLGHVEDDYILFDCPGQIELYTHLPVM
  KQLVQQLEQWEFRVCGVFLVDSQFMVESFKFISGILAALSAMISLEIPQVNIMTKMDLLS
  KKAKKEIEKFLDPDMYSLLEDSTSDLRSKKFKKLTKAICGLIDDYSMVRFLPYDQSDEES
  MNIVLQHIDFAIQYGEDLEFKEPKEREDESSSMFDEYFQECQDE
• Function: Small GTPase required for proper localization of RNA polymerase II (RNAPII). May act at an RNAP assembly step prior to nuclear import.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Trigeminal neuralgia	DIS31ZY6	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	moderate	Biomarker	[1]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[1]
Her2-receptor negative breast cancer	DISS605N	moderate	Altered Expression	[1]
HER2/NEU overexpressing breast cancer	DISYKID5	moderate	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of GPN-loop GTPase 3 (GPN3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of GPN-loop GTPase 3 (GPN3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of GPN-loop GTPase 3 (GPN3).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of GPN-loop GTPase 3 (GPN3).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of GPN-loop GTPase 3 (GPN3).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of GPN-loop GTPase 3 (GPN3).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of GPN-loop GTPase 3 (GPN3).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of GPN-loop GTPase 3 (GPN3).	[10]

References

• [1] Gpn3 Is Essential for Cell Proliferation of Breast Cancer Cells Independent of Their Malignancy Degree.Technol Cancer Res Treat. 2019 Jan 1;18:1533033819870823. doi: 10.1177/1533033819870823.
• [2] Nervus intermedius and the surgical management of geniculate neuralgia.J Neurosurg. 2018 Aug 10;131(2):343-351. doi: 10.3171/2018.3.JNS172920.
• [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] 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.
• [5] 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.
• [6] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.