Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR7MUS5)

• DOT Name: Probable G-protein coupled receptor 19 (GPR19)
• Synonyms: GPR-NGA
• Gene Name: GPR19
• Related Disease:
  Acute myocardial infarction
  Breast cancer
  Breast carcinoma
  Childhood acute lymphoblastic leukemia
  Lung cancer
  Lung carcinoma
  Systemic lupus erythematosus
• UniProt ID: GPR19_HUMAN
• Pfam ID: PF00001
• Sequence:
  MVFAHRMDNSKPHLIIPTLLVPLQNRSCTETATPLPSQYLMELSEEHSWMSNQTDLHYVL
  KPGEVATASIFFGILWLFSIFGNSLVCLVIHRSRRTQSTTNYFVVSMACADLLISVASTP
  FVLLQFTTGRWTLGSATCKVVRYFQYLTPGVQIYVLLSICIDRFYTIVYPLSFKVSREKA
  KKMIAASWVFDAGFVTPVLFFYGSNWDSHCNYFLPSSWEGTAYTVIHFLVGFVIPSVLII
  LFYQKVIKYIWRIGTDGRTVRRTMNIVPRTKVKTIKMFLILNLLFLLSWLPFHVAQLWHP
  HEQDYKKSSLVFTAITWISFSSSASKPTLYSIYNANFRRGMKETFCMSSMKCYRSNAYTI
  TTSSRMAKKNYVGISEIPSMAKTITKDSIYDSFDREAKEKKLAWPINSNPPNTFV
• Function: Orphan receptor.
• Tissue Specificity: Abundant expression in the brain.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Altered Expression	[4]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[4]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Probable G-protein coupled receptor 19 (GPR19).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Probable G-protein coupled receptor 19 (GPR19).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Probable G-protein coupled receptor 19 (GPR19).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Probable G-protein coupled receptor 19 (GPR19).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Probable G-protein coupled receptor 19 (GPR19).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Probable G-protein coupled receptor 19 (GPR19).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Probable G-protein coupled receptor 19 (GPR19).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Probable G-protein coupled receptor 19 (GPR19).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Probable G-protein coupled receptor 19 (GPR19).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Probable G-protein coupled receptor 19 (GPR19).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Probable G-protein coupled receptor 19 (GPR19).	[15]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Probable G-protein coupled receptor 19 (GPR19).	[16]

References

• [1] Inhibition of the LncRNA Gpr19 attenuates ischemia-reperfusion injury after acute myocardial infarction by inhibiting apoptosis and oxidative stress via the miR-324-5p/Mtfr1 axis.IUBMB Life. 2020 Mar;72(3):373-383. doi: 10.1002/iub.2187. Epub 2019 Oct 17.
• [2] G protein-coupled receptor GPR19 regulates E-cadherin expression and invasion of breast cancer cells.Biochim Biophys Acta Mol Cell Res. 2017 Jul;1864(7):1318-1327. doi: 10.1016/j.bbamcr.2017.05.001. Epub 2017 May 2.
• [3] Physical mapping of the G-protein coupled receptor 19 (GPR19) in the chromosome 12p12.3 region frequently rearranged in cancer cells.Hum Genet. 1999 Jul-Aug;105(1-2):162-4. doi: 10.1007/s004399900083.
• [4] Expression of G protein-coupled receptor 19 in human lung cancer cells is triggered by entry into S-phase and supports G(2)-M cell-cycle progression.Mol Cancer Res. 2012 Oct;10(10):1343-58. doi: 10.1158/1541-7786.MCR-12-0139. Epub 2012 Aug 21.
• [5] Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.Am J Hum Genet. 2013 Jan 10;92(1):41-51. doi: 10.1016/j.ajhg.2012.11.018. Epub 2012 Dec 27.
• [6] 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.
• [7] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [8] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] 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.
• [11] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [12] 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.
• [13] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.