Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGS3H0M)

• DOT Name: G-patch domain and KOW motifs-containing protein (GPKOW)
• Synonyms: G-patch domain-containing protein 5; Protein MOS2 homolog; Protein T54
• Gene Name: GPKOW
• Related Disease:
  Advanced cancer
  Atypical teratoid/rhabdoid tumour
  Depression
  Fetal growth restriction
  Isolated congenital microcephaly
  Neoplasm
  Non-small-cell lung cancer
  Holoprosencephaly-hypokinesia-congenital contractures syndrome
• UniProt ID: GPKOW_HUMAN
• PDB ID: 7DVQ; 7QTT; 8CH6
• Pfam ID: PF12656 ; PF00467
• Sequence:
  MADSKEGVLPLTAASTAPISFGFTRTSARRRLADSGDGAGPSPEEKDFLKTVEGRELQSV
  KPQEAPKELVIPLIQNGHRRQPPARPPGPSTDTGALADGVVSQAVKELIAESKKSLEERE
  NAGVDPTLAIPMIQKGCTPSGEGADSEPRAETVPEEANYEAVPVEAYGLAMLRGMGWKPG
  EGIGRTFNQVVKPRVNSLRPKGLGLGANLTEAQALTPTGPSRMPRPDEEQEKDKEDQPQG
  LVPGGAVVVLSGPHRGLYGKVEGLDPDNVRAMVRLAVGSRVVTVSEYYLRPVSQQEFDKN
  TLDLRQQNGTASSRKTLWNQELYIQQDNSERKRKHLPDRQDGPAAKSEKAAPRSQHWLHR
  DLRVRFVDNMYKGGQYYNTKMIIEDVLSPDTCVCRTDEGRVLEGLREDMLETLVPKAEGD
  RVMVVLGPQTGRVGHLLSRDRARSRALVQLPRENQVVELHYDAICQYMGPSDTDDD
• Function: RNA-binding protein involved in pre-mRNA splicing. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable).
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Atypical teratoid/rhabdoid tumour	DIS1FA0D	Strong	Biomarker	[2]
Depression	DIS3XJ69	Strong	Biomarker	[3]
Fetal growth restriction	DIS5WEJ5	Strong	Biomarker	[4]
Isolated congenital microcephaly	DISUXHZ6	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Holoprosencephaly-hypokinesia-congenital contractures syndrome	DISZGEKL	Limited	X-linked	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of G-patch domain and KOW motifs-containing protein (GPKOW).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of G-patch domain and KOW motifs-containing protein (GPKOW).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of G-patch domain and KOW motifs-containing protein (GPKOW).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of G-patch domain and KOW motifs-containing protein (GPKOW).	[13]
Selenium	DM25CGV	Approved	Selenium increases the expression of G-patch domain and KOW motifs-containing protein (GPKOW).	[14]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of G-patch domain and KOW motifs-containing protein (GPKOW).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of G-patch domain and KOW motifs-containing protein (GPKOW).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of G-patch domain and KOW motifs-containing protein (GPKOW).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of G-patch domain and KOW motifs-containing protein (GPKOW).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of G-patch domain and KOW motifs-containing protein (GPKOW).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of G-patch domain and KOW motifs-containing protein (GPKOW).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of G-patch domain and KOW motifs-containing protein (GPKOW).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of G-patch domain and KOW motifs-containing protein (GPKOW).	[12]

References

• [1] Nanoceria decorated flower-like molybdenum sulphide nanoflakes: an efficient nanozyme for tumour selective ROS generation and photo thermal therapy.Chem Commun (Camb). 2019 Jul 4;55(55):8017-8020. doi: 10.1039/c9cc03763b.
• [2] Controllable synthesis of MoS(2)@MoO(2) nanonetworks for enhanced NO(2) room temperature sensing in air.Nanoscale. 2019 Apr 25;11(17):8554-8564. doi: 10.1039/c9nr00137a.
• [3] 2D electric-double-layer phototransistor for photoelectronic and spatiotemporal hybrid neuromorphic integration.Nanoscale. 2019 Jan 17;11(3):1360-1369. doi: 10.1039/c8nr07133k.
• [4] Variant in the X-chromosome spliceosomal gene GPKOW causes male-lethal microcephaly with intrauterine growth restriction.Eur J Hum Genet. 2017 Sep;25(9):1078-1082. doi: 10.1038/ejhg.2017.97. Epub 2017 Jun 14.
• [5] Bottom-up synthesis of MoS(2) nanospheres for photothermal treatment of tumors.Photochem Photobiol Sci. 2018 Oct 10;17(10):1337-1345. doi: 10.1039/c8pp00198g.
• [6] Peritoneal carcinomatosis in non-small-cell lung cancer: retrospective multicentric analysis and literature review.Future Oncol. 2019 Mar;15(9):989-994. doi: 10.2217/fon-2018-0469. Epub 2019 Jan 25.
• [7] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [8] 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.
• [9] 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.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] 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.
• [12] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [13] 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.
• [14] 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.
• [15] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [16] 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.
• [17] 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.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.