Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKCF5AZ)

DOT Name	RPE-retinal G protein-coupled receptor (RGR)
Gene Name	RGR
Related Disease	Age-related macular degeneration ( ) Glioblastoma multiforme ( ) Inherited retinal dystrophy ( ) Retinal degeneration ( ) Retinopathy ( ) Retinitis pigmentosa ( ) Myopia ( ) Retinitis pigmentosa 44 ( )
UniProt ID	RGR_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00001
Sequence	MAETSALPTGFGELEVLAVGMVLLVEALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLAL ADSGISLNALVAATSSLLRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR SQLAWNSAVSLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDRNFTSFLFTM SFFNFAMPLFITITSYSLMEQKLGKSGHLQVNTTLPARTLLLGWGPYAILYLYAVIADVT SISPKLQMVPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKREKDRTK
Function	Receptor for all-trans- and 11-cis-retinal. Binds preferentially to the former and may catalyze the isomerization of the chromophore by a retinochrome-like mechanism.
Tissue Specificity	Preferentially expressed at high levels in the retinal pigment epithelium (RPE) and Mueller cells of the neural retina.
Reactome Pathway	Opsins (R-HSA-419771 ) G alpha (i) signalling events (R-HSA-418594 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Inherited retinal dystrophy	DISGGL77	Strong	Biomarker	[3]
Retinal degeneration	DISM1JHQ	Strong	Genetic Variation	[4]
Retinopathy	DISB4B0F	Strong	Genetic Variation	[5]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[6]
Myopia	DISK5S60	Limited	Genetic Variation	[7]
Retinitis pigmentosa 44	DIS68D74	Limited	Semidominant	[8]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of RPE-retinal G protein-coupled receptor (RGR).	[9]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of RPE-retinal G protein-coupled receptor (RGR).	[10]
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References

1	Exon-skipping variant of RGR opsin in human retina and pigment epithelium.Exp Eye Res. 2006 Jul;83(1):133-40. doi: 10.1016/j.exer.2005.11.013. Epub 2006 Mar 10.
2	Vascular targeting of LIGHT normalizes blood vessels in primary brain cancer and induces intratumoural high endothelial venules.J Pathol. 2018 Jun;245(2):209-221. doi: 10.1002/path.5080. Epub 2018 Apr 20.
3	Reevaluation of the Retinal Dystrophy Due to Recessive Alleles of RGR With the Discovery of a Cis-Acting Mutation in CDHR1.Invest Ophthalmol Vis Sci. 2016 Sep 1;57(11):4806-13. doi: 10.1167/iovs.16-19687.
4	Autosomal recessive retinitis pigmentosa and E150K mutation in the opsin gene.J Biol Chem. 2006 Aug 4;281(31):22289-22298. doi: 10.1074/jbc.M602664200. Epub 2006 May 31.
5	Clinical Features of a Retinopathy Associated With a Dominant Allele of the RGR Gene.Invest Ophthalmol Vis Sci. 2018 Oct 1;59(12):4812-4820. doi: 10.1167/iovs.18-25061.
6	Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
7	Detection and interpretation of shared genetic influences on 42 human traits.Nat Genet. 2016 Jul;48(7):709-17. doi: 10.1038/ng.3570. Epub 2016 May 16.
8	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.
9	Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
10	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.