Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT09TY4W)

• DOT Name: G patch domain-containing protein 2 (GPATCH2)
• Gene Name: GPATCH2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Hepatitis B virus infection
  Arthritis
  Proliferative diabetic retinopathy
• UniProt ID: GPTC2_HUMAN
• Pfam ID: PF01585
• Sequence:
  MFGAAGRQPIGAPAAGNSWHFSRTMEELVHDLVSALEESSEQARGGFAETGDHSRSISCP
  LKRQARKRRGRKRRSYNVHHPWETGHCLSEGSDSSLEEPSKDYRENHNNNKKDHSDSDDQ
  MLVAKRRPSSNLNNNVRGKRPLWHESDFAVDNVGNRTLRRRRKVKRMAVDLPQDISNKRT
  MTQPPEGCRDQDMDSDRAYQYQEFTKNKVKKRKLKIIRQGPKIQDEGVVLESEETNQTNK
  DKMECEEQKVSDELMSESDSSSLSSTDAGLFTNDEGRQGDDEQSDWFYEKESGGACGITG
  VVPWWEKEDPTELDKNVPDPVFESILTGSFPLMSHPSRRGFQARLSRLHGMSSKNIKKSG
  GTPTSMVPIPGPVGNKRMVHFSPDSHHHDHWFSPGARTEHDQHQLLRDNRAERGHKKNCS
  VRTASRQTSMHLGSLCTGDIKRRRKAAPLPGPTTAGFVGENAQPILENNIGNRMLQNMGW
  TPGSGLGRDGKGISEPIQAMQRPKGLGLGFPLPKSTSATTTPNAGKSA
• Function: Enhances the ATPase activity of DHX15 in vitro.
• Tissue Specificity: Testis.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[2]
Arthritis	DIST1YEL	Limited	Altered Expression	[3]
Proliferative diabetic retinopathy	DISQZ13G	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of G patch domain-containing protein 2 (GPATCH2).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of G patch domain-containing protein 2 (GPATCH2).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of G patch domain-containing protein 2 (GPATCH2).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of G patch domain-containing protein 2 (GPATCH2).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of G patch domain-containing protein 2 (GPATCH2).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of G patch domain-containing protein 2 (GPATCH2).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of G patch domain-containing protein 2 (GPATCH2).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of G patch domain-containing protein 2 (GPATCH2).	[12]
Nicotine	DMWX5CO	Approved	Nicotine increases the splicing of G patch domain-containing protein 2 (GPATCH2).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of G patch domain-containing protein 2 (GPATCH2).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of G patch domain-containing protein 2 (GPATCH2).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of G patch domain-containing protein 2 (GPATCH2).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of G patch domain-containing protein 2 (GPATCH2).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of G patch domain-containing protein 2 (GPATCH2).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of G patch domain-containing protein 2 (GPATCH2).	[21]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of G patch domain-containing protein 2 (GPATCH2).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of G patch domain-containing protein 2 (GPATCH2).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of G patch domain-containing protein 2 (GPATCH2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of G patch domain-containing protein 2 (GPATCH2).	[19]

References

• [1] Involvement of G-patch domain containing 2 overexpression in breast carcinogenesis.Cancer Sci. 2009 Aug;100(8):1443-50. doi: 10.1111/j.1349-7006.2009.01185.x. Epub 2009 May 4.
• [2] Antiviral therapeutic efficacy of foscarnet in hepatitis B virus infection.Antiviral Res. 2005 Dec;68(3):147-53. doi: 10.1016/j.antiviral.2005.09.002. Epub 2005 Oct 25.
• [3] Differential expression of three Chlamydia trachomatis hsp60-encoding genes in active vs. persistent infections.Microb Pathog. 2004 Jan;36(1):35-9. doi: 10.1016/j.micpath.2003.08.005.
• [4] Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control.Diabetes. 2019 Feb;68(2):441-456. doi: 10.2337/db18-0567. Epub 2018 Nov 28.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [8] 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.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] 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.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] 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.
• [19] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [20] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.