Details of Drug Off-Target (DOT)

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

• DOT Name: Opsin-5 (OPN5)
• Synonyms: G-protein coupled receptor 136; G-protein coupled receptor PGR12; Neuropsin; Transmembrane protein 13
• Gene Name: OPN5
• Related Disease:
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Cerebral infarction
  Dermatitis
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Mental disorder
  Ovarian cancer
  Ovarian neoplasm
  Schizophrenia
  Depression
  Status epilepticus seizure
  Temporal lobe epilepsy
• UniProt ID: OPN5_HUMAN
• Pfam ID: PF00001
• Sequence:
  MALNHTALPQDERLPHYLRDGDPFASKLSWEADLVAGFYLTIIGILSTFGNGYVLYMSSR
  RKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWIGCRWYGWAGFFFGCGS
  LITMTAVSLDRYLKICYLSYGVWLKRKHAYICLAAIWAYASFWTTMPLVGLGDYVPEPFG
  TSCTLDWWLAQASVGGQVFILNILFFCLLLPTAVIVFSYVKIIAKVKSSSKEVAHFDSRI
  HSSHVLEMKLTKVAMLICAGFLIAWIPYAVVSVWSAFGRPDSIPIQLSVVPTLLAKSAAM
  YNPIIYQVIDYKFACCQTGGLKATKKKSLEGFRLHTVTTVRKSSAVLEIHEEWE
• Function: G-protein coupled receptor which selectively activates G(i) type G proteins via ultraviolet A (UVA) light-mediated activation in the retina. Preferentially binds the chromophore 11-cis retinal and is a bistable protein that displays emission peaks at 380 nm (UVA light) and 470 nm (blue light). Required for the light-response in the inner plexiform layer, and contributes to the regulation of the light-response in the nerve fiber layer, via phosphorylated DAT/SLC6A3 dopamine uptake. Involved in local corneal and retinal circadian rhythm photoentrainment via modulation of the UVA light-induced phase-shift of the retina clock. Acts as a circadian photoreceptor in the outer ear, via modulation of circadian clock-gene expression in response to violet light during the light-to-dark transition phase and night phase of the circadian cycle. Required in the retina to negatively regulate hyaloid vessel regression during postnatal development via light-dependent OPN5-SLC32A1-DRD2-VEGFR2 signaling. Involved in the light-dependent regulation of retina and vitreous compartment dopamine levels.
• Tissue Specificity: Detected in brain and retina and cell lines derived from neural retina.
• Reactome Pathway:
  Opsins (R-HSA-419771)
  G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[3]
Dermatitis	DISY5SZC	Strong	Biomarker	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[1]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[5]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[5]
Schizophrenia	DISSRV2N	Strong	Biomarker	[1]
Depression	DIS3XJ69	Limited	Posttranslational Modification	[7]
Status epilepticus seizure	DISY3BIC	Limited	Altered Expression	[8]
Temporal lobe epilepsy	DISNOPXX	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Opsin-5 (OPN5).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Opsin-5 (OPN5).	[10]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Opsin-5 (OPN5).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Opsin-5 (OPN5).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Opsin-5 (OPN5).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Opsin-5 (OPN5).	[12]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Opsin-5 (OPN5).	[12]

References

• [1] Genetic variations of human neuropsin gene and psychiatric disorders: polymorphism screening and possible association with bipolar disorder and cognitive functions.Neuropsychopharmacology. 2008 Dec;33(13):3237-45. doi: 10.1038/npp.2008.29. Epub 2008 Mar 19.
• [2] Association of the progesterone receptor gene with breast cancer risk: a single-nucleotide polymorphism tagging approach.Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):675-82. doi: 10.1158/1055-9965.EPI-05-0679.
• [3] Targeted disruption of SPI3/Serpinb6 does not result in developmental or growth defects, leukocyte dysfunction, or susceptibility to stroke.Mol Cell Biol. 2004 May;24(9):4075-82. doi: 10.1128/MCB.24.9.4075-4082.2004.
• [4] Molecular mechanism of kallikrein-related peptidase 8/neuropsin-induced hyperkeratosis in inflamed skin.Br J Dermatol. 2010 Sep;163(3):466-75. doi: 10.1111/j.1365-2133.2010.09864.x. Epub 2010 Aug 12.
• [5] The human KLK8 (neuropsin/ovasin) gene: identification of two novel splice variants and its prognostic value in ovarian cancer. Clin Cancer Res. 2001 Apr;7(4):806-11.
• [6] RNA stability regulates differential expression of the metastasis protein, osteopontin, in hepatocellular cancer.Surgery. 2008 Jun;143(6):803-12. doi: 10.1016/j.surg.2008.02.005. Epub 2008 Apr 18.
• [7] Epigenome-wide association study of depression symptomatology in elderly monozygotic twins.Transl Psychiatry. 2019 Sep 2;9(1):214. doi: 10.1038/s41398-019-0548-9.
• [8] Ablation of neuropsin-neuregulin 1 signaling imbalances ErbB4 inhibitory networks and disrupts hippocampal gamma oscillation.Transl Psychiatry. 2017 Mar 7;7(3):e1052. doi: 10.1038/tp.2017.20.
• [9] 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.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [13] 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.