Details of Drug Off-Target (DOT)

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

• DOT Name: Gamma-aminobutyric acid receptor subunit gamma-3 (GABRG3)
• Synonyms: GABA(A) receptor subunit gamma-3
• Gene Name: GABRG3
• UniProt ID: GBRG3_HUMAN
• Pfam ID: PF02931 ; PF02932
• Sequence:
  MAPKLLLLLCLFSGLHARSRKVEEDEYEDSSSNQKWVLAPKSQDTDVTLILNKLLREYDK
  KLRPDIGIKPTVIDVDIYVNSIGPVSSINMEYQIDIFFAQTWTDSRLRFNSTMKILTLNS
  NMVGLIWIPDTIFRNSKTAEAHWITTPNQLLRIWNDGKILYTLRLTINAECQLQLHNFPM
  DEHSCPLIFSSYGYPKEEMIYRWRKNSVEAADQKSWRLYQFDFMGLRNTTEIVTTSAGDY
  VVMTIYFELSRRMGYFTIQTYIPCILTVVLSWVSFWIKKDATPARTALGITTVLTMTTLS
  TIARKSLPRVSYVTAMDLFVTVCFLFVFAALMEYATLNYYSSCRKPTTTKKTTSLLHPDS
  SRWIPERISLQAPSNYSLLDMRPPPTAMITLNNSVYWQEFEDTCVYECLDGKDCQSFFCC
  YEECKSGSWRKGRIHIDILELDSYSRVFFPTSFLLFNLVYWVGYLYL
• Function: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Retrograde endocan.binoid sig.ling (hsa04723)
  GABAergic sy.pse (hsa04727)
  Morphine addiction (hsa05032)
  Nicotine addiction (hsa05033)
• Reactome Pathway:
  GABA receptor activation (R-HSA-977443)
  Signaling by ERBB4 (R-HSA-1236394)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Gamma-aminobutyric acid receptor subunit gamma-3 (GABRG3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Gamma-aminobutyric acid receptor subunit gamma-3 (GABRG3).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Gamma-aminobutyric acid receptor subunit gamma-3 (GABRG3).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Gamma-aminobutyric acid receptor subunit gamma-3 (GABRG3).	[2]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Gamma-aminobutyric acid receptor subunit gamma-3 (GABRG3).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Gamma-aminobutyric acid receptor subunit gamma-3 (GABRG3).	[4]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [3] Gonadal steroids regulate GABAA receptor subunit mRNA expression in NT2-N neurons. Brain Res Mol Brain Res. 2005 Aug 18;138(2):105-15. doi: 10.1016/j.molbrainres.2004.10.047.
• [4] 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.
• [5] 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.
• [6] 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.