Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHS1L0E)

• DOT Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7)
• Synonyms: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
• Gene Name: GNG7
• UniProt ID: GBG7_HUMAN
• Pfam ID: PF00631
• Sequence:
  MSATNNIAQARKLVEQLRIEAGIERIKVSKAASDLMSYCEQHARNDPLLVGVPASENPFK
  DKKPCIIL
• Function: Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Plays a role in the regulation of adenylyl cyclase signaling in certain regions of the brain. Plays a role in the formation or stabilzation of a G protein heterotrimer (G(olf) subunit alpha-beta-gamma-7) that is required for adenylyl cyclase activity in the striatum.
• Tissue Specificity: Expressed in a variety of tissues. Down-regulated in pancreatic and esophageal cancer.
• KEGG Pathway:
  Ras sig.ling pathway (hsa04014)
  Chemokine sig.ling pathway (hsa04062)
  PI3K-Akt sig.ling pathway (hsa04151)
  Apelin sig.ling pathway (hsa04371)
  Circadian entrainment (hsa04713)
  Retrograde endocan.binoid sig.ling (hsa04723)
  Glutamatergic sy.pse (hsa04724)
  Cholinergic sy.pse (hsa04725)
  Serotonergic sy.pse (hsa04726)
  GABAergic sy.pse (hsa04727)
  Dopaminergic sy.pse (hsa04728)
  Olfactory transduction (hsa04740)
  Relaxin sig.ling pathway (hsa04926)
  Morphine addiction (hsa05032)
  Alcoholism (hsa05034)
  Human cytomegalovirus infection (hsa05163)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Human immunodeficiency virus 1 infection (hsa05170)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  Glucagon signaling in metabolic regulation (R-HSA-163359)
  G-protein activation (R-HSA-202040)
  Glucagon-like Peptide-1 (GLP1) regulates insulin secretion (R-HSA-381676)
  ADP signalling through P2Y purinoceptor 12 (R-HSA-392170)
  G beta (R-HSA-392451)
  Prostacyclin signalling through prostacyclin receptor (R-HSA-392851)
  Adrenaline,noradrenaline inhibits insulin secretion (R-HSA-400042)
  Ca2+ pathway (R-HSA-4086398)
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (12/13) signalling events (R-HSA-416482)
  G beta (R-HSA-418217)
  G alpha (s) signalling events (R-HSA-418555)
  ADP signalling through P2Y purinoceptor 1 (R-HSA-418592)
  G alpha (i) signalling events (R-HSA-418594)
  G alpha (z) signalling events (R-HSA-418597)
  Glucagon-type ligand receptors (R-HSA-420092)
  Thromboxane signalling through TP receptor (R-HSA-428930)
  Vasopressin regulates renal water homeostasis via Aquaporins (R-HSA-432040)
  Thrombin signalling through proteinase activated receptors (PARs) (R-HSA-456926)
  Presynaptic function of Kainate receptors (R-HSA-500657)
  Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding (R-HSA-6814122)
  G beta (R-HSA-8964315)
  G beta (R-HSA-8964616)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  GPER1 signaling (R-HSA-9634597)
  ADORA2B mediated anti-inflammatory cytokines production (R-HSA-9660821)
  Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits (R-HSA-997272)
  Activation of G protein gated Potassium channels (R-HSA-1296041)

Molecular Interaction Atlas (MIA) of This DOT

12 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 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[14]

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 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[5]
Azacitidine	DMTA5OE	Approved	Azacitidine affects the methylation of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 (GNG7).	[11]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] 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.
• [3] 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.
• [4] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [5] 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.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer. Br J Cancer. 2008 Jan 29;98(2):410-7. doi: 10.1038/sj.bjc.6604124. Epub 2008 Jan 22.
• [9] 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.
• [10] The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
• [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] 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.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.