Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGAT70V)

• DOT Name: G protein-coupled receptor 88 (GPR88)
• Synonyms: Striatum-specific G-protein coupled receptor
• Gene Name: GPR88
• Related Disease: Chorea, childhood-onset, with psychomotor retardation
• UniProt ID: GPR88_HUMAN
• PDB ID: 7EJX; 7WZ4
• Pfam ID: PF00001
• Sequence:
  MTNSSSTSTSSTTGGSLLLLCEEEESWAGRRIPVSLLYSGLAIGGTLANGMVIYLVSSFR
  KLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPTGSAEPPADWDGAGGSYRLLRGGLL
  GLGLTVSLLSHCLVALNRYLLITRAPATYQALYQRRHTAGMLALSWALALGLVLLLPPWA
  PRPGAAPPRVHYPALLAAAALLAQTALLLHCYLGIVRRVRVSVKRVSVLNFHLLHQLPGC
  AAAAAAFPGAQHAPGPGGAAHPAQAQPLPPALHPRRAQRRLSGLSVLLLCCVFLLATQPL
  VWVSLASGFSLPVPWGVQAASWLLCCALSALNPLLYTWRNEEFRRSVRSVLPGVGDAAAA
  AVAATAVPAVSQAQLGTRAAGQHW
• Function: Orphan G protein-coupled receptor implicated in a large repertoire of behavioral responses that engage motor activities, spatial learning, and emotional processing. May play a role in the regulation of cognitive and motor function. Couples with the heterotrimeric G protein complex of the G(i) subfamily, consisting of GNAI1, GNB1 and GNG2, thereby acting through a G(i)-mediated pathway. Plays a role in the attenuation of D1 dopamine receptor (D1R)-mediated cAMP response in ciliated cells. In non-ciliated cells, involved in the inhibition of the beta-2 adrenergic receptor (B2AR) response.
• Tissue Specificity: Expressed predominantly in the striatum.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chorea, childhood-onset, with psychomotor retardation	DISEGMKF	Limited	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of G protein-coupled receptor 88 (GPR88).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of G protein-coupled receptor 88 (GPR88).	[3]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of G protein-coupled receptor 88 (GPR88).	[4]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of G protein-coupled receptor 88 (GPR88).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of G protein-coupled receptor 88 (GPR88).	[6]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [5] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [6] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.