Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0M5TNY)

• DOT Name: Growth arrest-specific protein 7 (GAS7)
• Synonyms: GAS-7
• Gene Name: GAS7
• Related Disease:
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  leukaemia
  Lung squamous cell carcinoma
  Neoplasm
  Obesity
  Schizophrenia
  Ulcerative colitis
  Leukemia
  OPTN-related open angle glaucoma
  Lung cancer
  Lung carcinoma
• UniProt ID: GAS7_HUMAN
• PDB ID: 2LX7; 2YSH
• Pfam ID: PF00611 ; PF14604 ; PF00397 ; PF16623
• Sequence:
  MSGARCRTLYPFSGERHGQGLRFAAGELITLLQVPDGGWWEGEKEDGLRGWFPASYVQLL
  EKPGMVPPPPGEESQTVILPPGWQSYLSPQGRRYYVNTTTNETTWERPSSSPGIPASPGS
  HRSSLPPTVNGYHASGTPAHPPETAHMSVRKSTGDSQNLGSSSPSKKQSKENTITINCVT
  FPHPDTMPEQQLLKPTEWSYCDYFWADKKDPQGNGTVAGFELLLQKQLKGKQMQKEMSEF
  IRERIKIEEDYAKNLAKLSQNSLASQEEGSLGEAWAQVKKSLADEAEVHLKFSAKLHSEV
  EKPLMNFRENFKKDMKKCDHHIADLRKQLASRYASVEKARKALTERQRDLEMKTQQLEIK
  LSNKTEEDIKKARRKSTQAGDDLMRCVDLYNQAQSKWFEEMVTTTLELERLEVERVEMIR
  QHLCQYTQLRHETDMFNQSTVEPVDQLLRKVDPAKDRELWVREHKTGNIRPVDMEI
• Function: May play a role in promoting maturation and morphological differentiation of cerebellar neurons.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
leukaemia	DISS7D1V	Strong	Genetic Variation	[5]
Lung squamous cell carcinoma	DISXPIBD	Strong	Altered Expression	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Obesity	DIS47Y1K	Strong	Biomarker	[8]
Schizophrenia	DISSRV2N	Strong	Biomarker	[2]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[9]
Leukemia	DISNAKFL	moderate	Biomarker	[10]
OPTN-related open angle glaucoma	DISDR98A	moderate	Genetic Variation	[11]
Lung cancer	DISCM4YA	Limited	Biomarker	[7]
Lung carcinoma	DISTR26C	Limited	Biomarker	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Growth arrest-specific protein 7 (GAS7) increases the Neutropenia ADR of Chlorothiazide.	[30]

16 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 Growth arrest-specific protein 7 (GAS7).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Growth arrest-specific protein 7 (GAS7).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Growth arrest-specific protein 7 (GAS7).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Growth arrest-specific protein 7 (GAS7).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Growth arrest-specific protein 7 (GAS7).	[17]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Growth arrest-specific protein 7 (GAS7).	[18]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Growth arrest-specific protein 7 (GAS7).	[19]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Growth arrest-specific protein 7 (GAS7).	[18]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Growth arrest-specific protein 7 (GAS7).	[20]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Growth arrest-specific protein 7 (GAS7).	[21]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Growth arrest-specific protein 7 (GAS7).	[22]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol affects the expression of Growth arrest-specific protein 7 (GAS7).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Growth arrest-specific protein 7 (GAS7).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Growth arrest-specific protein 7 (GAS7).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Growth arrest-specific protein 7 (GAS7).	[28]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Growth arrest-specific protein 7 (GAS7).	[29]

3 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 Growth arrest-specific protein 7 (GAS7).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Growth arrest-specific protein 7 (GAS7).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Growth arrest-specific protein 7 (GAS7).	[26]

References

• [1] MLL/GAS7 fusion in a pediatric case of t(11;17)(q23;p13)-positive precursor B-cell acute lymphoblastic leukemia.Haematologica. 2006 Sep;91(9):1287-8.
• [2] Solution NMR structure and ligand identification of human Gas7 SH3 domain reveal a typical SH3 fold but a non-canonical ligand-binding mode.Biochem Biophys Res Commun. 2019 Sep 3;516(4):1190-1195. doi: 10.1016/j.bbrc.2019.07.004. Epub 2019 Jul 9.
• [3] Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7-CYFIP1-mediated signaling pathway.Oncogene. 2018 Jul;37(30):4137-4150. doi: 10.1038/s41388-018-0253-9. Epub 2018 Apr 30.
• [4] DNA methylome profiling identifies novel methylated genes in African American patients with colorectal neoplasia.Epigenetics. 2014 Apr;9(4):503-12. doi: 10.4161/epi.27644. Epub 2014 Jan 17.
• [5] Detection of leukemia-associated MLL-GAS7 translocation early during chemotherapy with DNA topoisomerase II inhibitors.Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2814-9. doi: 10.1073/pnas.050397097.
• [6] Minimal deletion regions in lung squamous cell carcinoma: association with abnormality of the DNA double-strand break repair genes and their applications on gene identification and prognostic biomarkers.Lung Cancer. 2008 Mar;59(3):332-9. doi: 10.1016/j.lungcan.2007.08.038. Epub 2007 Nov 1.
• [7] Oxaliplatin inhibits proliferation and migration of human hepatocellular carcinoma cells via GAS7C and the N-WASP/FAK/F-actin pathway.Acta Biochim Biophys Sin (Shanghai). 2017 Jul 1;49(7):581-587. doi: 10.1093/abbs/gmx046.
• [8] Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks.Nat Genet. 2009 Apr;41(4):415-23. doi: 10.1038/ng.325. Epub 2009 Mar 8.
• [9] Genetic analysis in a Dutch study sample identifies more ulcerative colitis susceptibility loci and shows their additive role in disease risk.Am J Gastroenterol. 2010 Feb;105(2):395-402. doi: 10.1038/ajg.2009.576. Epub 2009 Oct 27.
• [10] MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice.Cancer Cell. 2003 Feb;3(2):161-71. doi: 10.1016/s1535-6108(03)00019-9.
• [11] Association of polymorphism rs11656696 in GAS7 with primary open-Angle Glaucoma in a Chinese Population.Ophthalmic Genet. 2019 Jun;40(3):237-241. doi: 10.1080/13816810.2019.1627465. Epub 2019 Jul 4.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor alpha and enhancing changes in all-trans-retinoic acid-regulated gene expression. Cancer Res. 2005 Sep 1;65(17):7856-65. doi: 10.1158/0008-5472.CAN-05-1056.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [18] 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.
• [19] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [20] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [21] Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
• [22] 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.
• [23] Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. J Exp Med. 2010 Apr 12;207(4):731-50. doi: 10.1084/jem.20091488. Epub 2010 Apr 5.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [29] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [30] Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer Sci. 2013 Aug;104(8):1074-82. doi: 10.1111/cas.12186. Epub 2013 Jun 10.