Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMPNSE7)

• DOT Name: Glia maturation factor gamma (GMFG)
• Synonyms: GMF-gamma
• Gene Name: GMFG
• Related Disease:
  Cardiovascular disease
  Colorectal carcinoma
  Coronary atherosclerosis
  Metabolic disorder
  Myocardial ischemia
  Epithelial ovarian cancer
• UniProt ID: GMFG_HUMAN
• PDB ID: 3L50
• Pfam ID: PF00241
• Sequence:
  MSDSLVVCEVDPELTEKLRKFRFRKETDNAAIIMKVDKDRQMVVLEEEFQNISPEELKME
  LPERQPRFVVYSYKYVHDDGRVSYPLCFIFSSPVGCKPEQQMMYAGSKNRLVQTAELTKV
  FEIRTTDDLTEAWLQEKLSFFR
• Tissue Specificity: Expressed predominantly in lung, heart and placenta.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Coronary atherosclerosis	DISKNDYU	Strong	Altered Expression	[1]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[3]
Myocardial ischemia	DISFTVXF	Strong	Altered Expression	[1]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[4]

7 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 Glia maturation factor gamma (GMFG).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glia maturation factor gamma (GMFG).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Glia maturation factor gamma (GMFG).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glia maturation factor gamma (GMFG).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glia maturation factor gamma (GMFG).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Glia maturation factor gamma (GMFG).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Glia maturation factor gamma (GMFG).	[12]

1 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 Glia maturation factor gamma (GMFG).	[11]

References

• [1] Glia maturation factor-gamma is preferentially expressed in microvascular endothelial and inflammatory cells and modulates actin cytoskeleton reorganization.Circ Res. 2006 Aug 18;99(4):424-33. doi: 10.1161/01.RES.0000237662.23539.0b. Epub 2006 Jul 27.
• [2] Expression of glia maturation factor is associated with colorectal cancer metastasis and its downregulation suppresses colorectal cancer cell migration and invasion in vitro.Oncol Rep. 2017 Feb;37(2):929-936. doi: 10.3892/or.2017.5361. Epub 2017 Jan 9.
• [3] Glia maturation factor- regulates murine macrophage iron metabolism and M2 polarization through mitochondrial ROS.Blood Adv. 2019 Apr 23;3(8):1211-1225. doi: 10.1182/bloodadvances.2018026070.
• [4] High GMFG expression correlates with poor prognosis and promotes cell migration and invasion in epithelial ovarian cancer.Gynecol Oncol. 2014 Mar;132(3):745-51. doi: 10.1016/j.ygyno.2014.01.044. Epub 2014 Jan 31.
• [5] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] 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.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.