Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT33SU2R)

• DOT Name: Rhodopsin (RHO)
• Synonyms: Opsin-2
• Gene Name: RHO
• Related Disease:
  Congenital stationary night blindness autosomal dominant 1
  Retinitis pigmentosa 4
  Congenital stationary night blindness
  Retinitis pigmentosa
  Fundus albipunctatus
• UniProt ID: OPSD_HUMAN
• PDB ID: 4ZWJ; 5DGY; 5W0P; 6CMO
• Pfam ID: PF00001 ; PF10413
• Sequence:
  MNGTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLY
  VTVQHKKLRTPLNYILLNLAVADLFMVLGGFTSTLYTSLHGYFVFGPTGCNLEGFFATLG
  GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLAGWSRYIP
  EGLQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIIIFFCYGQLVFTVKEAAAQQQES
  ATTQKAEKEVTRMVIIMVIAFLICWVPYASVAFYIFTHQGSNFGPIFMTIPAFFAKSAAI
  YNPVIYIMMNKQFRNCMLTTICCGKNPLGDDEASATVSKTETSQVAPA
• Function: Photoreceptor required for image-forming vision at low light intensity. Required for photoreceptor cell viability after birth. Light-induced isomerization of the chromophore 11-cis-retinal to all-trans-retinal triggers a conformational change that activates signaling via G-proteins. Subsequent receptor phosphorylation mediates displacement of the bound G-protein alpha subunit by the arrestin SAG and terminates signaling.
• Tissue Specificity: Rod shaped photoreceptor cells which mediate vision in dim light.
• KEGG Pathway: Phototransduction (hsa04744)
• Reactome Pathway:
  Activation of the phototransduction cascade (R-HSA-2485179)
  Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859)
  G alpha (i) signalling events (R-HSA-418594)
  Opsins (R-HSA-419771)
  VxPx cargo-targeting to cilium (R-HSA-5620916)
  The canonical retinoid cycle in rods (twilight vision) (R-HSA-2453902)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital stationary night blindness autosomal dominant 1	DISFPXWP	Definitive	Autosomal dominant	[1]
Retinitis pigmentosa 4	DIS4ZDFZ	Definitive	Semidominant	[2]
Congenital stationary night blindness	DISX0CWK	Supportive	Autosomal dominant	[3]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[4]
Fundus albipunctatus	DISNICY6	Limited	Unknown	[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 Rhodopsin (RHO).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Rhodopsin (RHO).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Rhodopsin (RHO).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Rhodopsin (RHO).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Rhodopsin (RHO).	[10]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Rhodopsin (RHO).	[11]

References

• [1] Heterozygous missense mutation in the rhodopsin gene as a cause of congenital stationary night blindness. Nat Genet. 1993 Jul;4(3):280-3. doi: 10.1038/ng0793-280.
• [2] 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.
• [3] A novel mutation within the rhodopsin gene (Thr-94-Ile) causing autosomal dominant congenital stationary night blindness. Hum Mutat. 1999;13(1):75-81. doi: 10.1002/(SICI)1098-1004(1999)13:1<75::AID-HUMU9>3.0.CO;2-4.
• [4] 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.
• [5] Retinitis punctata albescens associated with the Arg135Trp mutation in the rhodopsin gene. Am J Ophthalmol. 1996 Jan;121(1):19-25. doi: 10.1016/s0002-9394(14)70530-6.
• [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] 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.
• [8] 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.
• [9] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Protective Effects of a Rho Kinase Inhibitor on Paraquat-Induced Acute Lung Injuries in Rats. Inflammation. 2018 Dec;41(6):2171-2183. doi: 10.1007/s10753-018-0860-1.