Details of Drug Off-Target (DOT)

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

• DOT Name: G-protein coupled receptor 22 (GPR22)
• Gene Name: GPR22
• Related Disease: Osteoarthritis
• UniProt ID: GPR22_HUMAN
• Pfam ID: PF00001
• Sequence:
  MCFSPILEINMQSESNITVRDDIDDINTNMYQPLSYPLSFQVSLTGFLMLEIVLGLGSNL
  TVLVLYCMKSNLINSVSNIITMNLHVLDVIICVGCIPLTIVILLLSLESNTALICCFHEA
  CVSFASVSTAINVFAITLDRYDISVKPANRILTMGRAVMLMISIWIFSFFSFLIPFIEVN
  FFSLQSGNTWENKTLLCVSTNEYYTELGMYYHLLVQIPIFFFTVVVMLITYTKILQALNI
  RIGTRFSTGQKKKARKKKTISLTTQHEATDMSQSSGGRNVVFGVRTSVSVIIALRRAVKR
  HRERRERQKRVFRMSLLIISTFLLCWTPISVLNTTILCLGPSDLLVKLRLCFLVMAYGTT
  IFHPLLYAFTRQKFQKVLKSKMKKRVVSIVEADPLPNNAVIHNSWIDPKRNKKITFEDSE
  IREKCLVPQVVTD
• Function: Orphan G-protein coupled receptor. Seems to act through a G(i)/G(o) mediated pathway. May be involved in ciliogenesis.
• Tissue Specificity: High expression in adult and fetal heart tissue . Expressed in the brain, with enrichment in the accumbens, amygdala, cerebellum, cortex, and hippocampus regions .

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of G-protein coupled receptor 22 (GPR22).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of G-protein coupled receptor 22 (GPR22).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of G-protein coupled receptor 22 (GPR22).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of G-protein coupled receptor 22 (GPR22).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of G-protein coupled receptor 22 (GPR22).	[6]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of G-protein coupled receptor 22 (GPR22).	[7]

References

• [1] Gene expression analysis reveals HBP1 as a key target for the osteoarthritis susceptibility locus that maps to chromosome 7q22.Ann Rheum Dis. 2012 Dec;71(12):2020-7. doi: 10.1136/annrheumdis-2012-201304. Epub 2012 May 14.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] 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.
• [6] 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.
• [7] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.