Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1LZ7TS)

DOT Name	Melanopsin (OPN4)
Synonyms	Opsin-4
Gene Name	OPN4
Related Disease	Chromosomal disorder ( ) Mood disorder ( ) Non-insulin dependent diabetes ( ) Alzheimer disease ( ) Brain disease ( ) Cardiac failure ( ) Cataract ( ) Cerebral infarction ( ) Cocaine addiction ( ) Congestive heart failure ( ) Coronary atherosclerosis ( ) Coronary heart disease ( ) Depression ( ) Diabetic retinopathy ( ) Fanconi anemia complementation group A ( ) Fanconi's anemia ( ) Hepatocellular carcinoma ( ) Huntington disease ( ) Major depressive disorder ( ) Matthew-Wood syndrome ( ) Migraine disorder ( ) Mitochondrial disease ( ) Multiple sclerosis ( ) Neuralgia ( ) Neuroblastoma ( ) Obstructive sleep apnea ( ) Opioid dependence ( ) Paracoccidioidomycosis ( ) Parkinson disease ( ) Peripheral arterial disease ( ) Psoriasis ( ) Retinitis pigmentosa ( ) Tuberculosis ( ) Vitiligo ( ) Advanced cancer ( ) Alcohol dependence ( ) Cholestasis ( ) Chronic graft versus host disease ( ) Lung cancer ( ) Lung carcinoma ( ) Neoplasm ( ) Primary cutaneous T-cell lymphoma ( ) Choroideremia ( ) Ocular hypertension ( ) Sleep disorder ( )
UniProt ID	OPN4_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00001
Sequence	MNPPSGPRVPPSPTQEPSCMATPAPPSWWDSSQSSISSLGRLPSISPTAPGTWAAAWVPL PTVDVPDHAHYTLGTVILLVGLTGMLGNLTVIYTFCRSRSLRTPANMFIINLAVSDFLMS FTQAPVFFTSSLYKQWLFGETGCEFYAFCGALFGISSMITLTAIALDRYLVITRPLATFG VASKRRAAFVLLGVWLYALAWSLPPFFGWSAYVPEGLLTSCSWDYMSFTPAVRAYTMLLC CFVFFLPLLIIIYCYIFIFRAIRETGRALQTFGACKGNGESLWQRQRLQSECKMAKIMLL VILLFVLSWAPYSAVALVAFAGYAHVLTPYMSSVPAVIAKASAIHNPIIYAITHPKYRVA IAQHLPCLGVLLGVSRRHSRPYPSYRSTHRSTLTSHTSNLSWISIRRRQESLGSESEVGW THMEAAAVWGAAQQANGRSLYGQGLEDLEAKAPPRPQGHEAETPGKTKGLIPSQDPRM
Function	Photoreceptor that binds cis-retinaldehydes. Contributes to pupillar reflex, photoentrainment and other non-image forming responses to light. May be involved in the optokinetic visual tracking response. May be involved in the regulation of retinal hyaloid vessel growth and regression.
Tissue Specificity	Expressed in the retina.
Reactome Pathway	Opsins (R-HSA-419771 ) G alpha (q) signalling events (R-HSA-416476 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Chromosomal disorder	DISM5BB5	Definitive	Biomarker	[1]
Mood disorder	DISLVMWO	Definitive	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Brain disease	DIS6ZC3X	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Altered Expression	[6]
Cataract	DISUD7SL	Strong	Biomarker	[7]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[8]
Cocaine addiction	DISHTRXG	Strong	Biomarker	[9]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[6]
Coronary atherosclerosis	DISKNDYU	Strong	Altered Expression	[6]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[6]
Depression	DIS3XJ69	Strong	Biomarker	[10]
Diabetic retinopathy	DISHGUJM	Strong	Biomarker	[11]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[12]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[13]
Huntington disease	DISQPLA4	Strong	Altered Expression	[14]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[10]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[15]
Migraine disorder	DISFCQTG	Strong	Biomarker	[11]
Mitochondrial disease	DISKAHA3	Strong	Biomarker	[16]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[5]
Neuralgia	DISWO58J	Strong	Biomarker	[17]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[18]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[19]
Opioid dependence	DIS6WEHK	Strong	Biomarker	[20]
Paracoccidioidomycosis	DIS88F55	Strong	Biomarker	[21]
Parkinson disease	DISQVHKL	Strong	Biomarker	[22]
Peripheral arterial disease	DIS78WFB	Strong	Genetic Variation	[23]
Psoriasis	DIS59VMN	Strong	Altered Expression	[24]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[25]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[21]
Vitiligo	DISR05SL	Strong	Biomarker	[26]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[27]
Alcohol dependence	DIS4ZSCO	moderate	Biomarker	[28]
Cholestasis	DISDJJWE	moderate	Biomarker	[24]
Chronic graft versus host disease	DIS1MM9J	moderate	Biomarker	[29]
Lung cancer	DISCM4YA	moderate	Genetic Variation	[30]
Lung carcinoma	DISTR26C	moderate	Genetic Variation	[30]
Neoplasm	DISZKGEW	moderate	Biomarker	[31]
Primary cutaneous T-cell lymphoma	DIS35WVW	Disputed	Biomarker	[18]
Choroideremia	DISH4N9B	Limited	Biomarker	[32]
Ocular hypertension	DISC2BT9	Limited	Biomarker	[33]
Sleep disorder	DIS3JP1U	Limited	Genetic Variation	[34]
------------------------------------------------------------------------------------


⏷ Show the Full List of 45 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

3 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 Melanopsin (OPN4).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Melanopsin (OPN4).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Melanopsin (OPN4).	[37]
------------------------------------------------------------------------------------

References

1	Studies of DNA and chromosome damage in skin fibroblasts and blood lymphocytes from psoriasis patients treated with 8-methoxypsoralen and UVA irradiation.J Invest Dermatol. 1983 Aug;81(2):93-7. doi: 10.1111/1523-1747.ep12542161.
2	Melanopsin, photosensitive ganglion cells, and seasonal affective disorder.Neurosci Biobehav Rev. 2013 Mar;37(3):229-39. doi: 10.1016/j.neubiorev.2012.12.009. Epub 2012 Dec 31.
3	Outer Retinal Structure and Function Deficits Contribute to Circadian Disruption in Patients With Type 2 Diabetes.Invest Ophthalmol Vis Sci. 2019 May 1;60(6):1870-1878. doi: 10.1167/iovs.18-26297.
4	Light-Induced Pupillary Responses in Alzheimer's Disease.Front Neurol. 2019 Apr 12;10:360. doi: 10.3389/fneur.2019.00360. eCollection 2019.
5	Retinal Architecture and Melanopsin-Mediated Pupillary Response Characteristics: A Putative Pathophysiologic Signature for the Retino-Hypothalamic Tract in Multiple Sclerosis.JAMA Neurol. 2017 May 1;74(5):574-582. doi: 10.1001/jamaneurol.2016.5131.
6	Assessment of nociceptin/orphanin FQ and micro-opioid receptor mRNA in the human right atrium.Br J Anaesth. 2010 Jun;104(6):698-704. doi: 10.1093/bja/aeq089. Epub 2010 Apr 21.
7	Melanopsin-Mediated Acute Light Responses Measured in Winter and in Summer: Seasonal Variations in Adults with and without Cataracts.Front Neurol. 2017 Sep 11;8:464. doi: 10.3389/fneur.2017.00464. eCollection 2017.
8	Protective effects of 8-MOP on blood-brain barrier via the Nrf-2/HO-1 pathway in mice model of cerebral infarction.Eur Rev Med Pharmacol Sci. 2018 Jul;22(13):4278-4287. doi: 10.26355/eurrev_201807_15424.
9	Cebranopadol, a Mixed Opioid Agonist, Reduces Cocaine Self-administration through Nociceptin Opioid and Mu Opioid Receptors.Front Psychiatry. 2017 Nov 13;8:234. doi: 10.3389/fpsyt.2017.00234. eCollection 2017.
10	Melanopsin-Driven Pupil Response and Light Exposure in Non-seasonal Major Depressive Disorder.Front Neurol. 2018 Sep 13;9:764. doi: 10.3389/fneur.2018.00764. eCollection 2018.
11	Melanopsin-expressing retinal ganglion cells in aging and disease.Histol Histopathol. 2019 Dec;34(12):1299-1311. doi: 10.14670/HH-18-138. Epub 2019 Jun 20.
12	Comparison of the sensitivity of Fanconi's anemia and normal fibroblasts to the induction of sister-chromatid exchanges by photoaddition of mono- and bi-functional psoralens.Mutat Res. 1986 Jul;174(3):241-6. doi: 10.1016/0165-7992(86)90158-2.
13	The mu-opioid receptor is a molecular marker for poor prognosis in hepatocellular carcinoma and represents a potential therapeutic target.Br J Anaesth. 2019 Jun;122(6):e157-e167. doi: 10.1016/j.bja.2018.09.030. Epub 2018 Dec 12.
14	Degeneration of ipRGCs in Mouse Models of Huntington's Disease Disrupts Non-Image-Forming Behaviors Before Motor Impairment.J Neurosci. 2019 Feb 20;39(8):1505-1524. doi: 10.1523/JNEUROSCI.0571-18.2018. Epub 2018 Dec 26.
15	Glucose metabolic phenotype of pancreatic cancer.World J Gastroenterol. 2016 Mar 28;22(12):3471-85. doi: 10.3748/wjg.v22.i12.3471.
16	Chromatic Pupillometry Methods for Assessing Photoreceptor Health in Retinal and Optic Nerve Diseases.Front Neurol. 2019 Feb 12;10:76. doi: 10.3389/fneur.2019.00076. eCollection 2019.
17	Selectivity profiling of NOP, MOP, DOP and KOP receptor antagonists in the rat spinal nerve ligation model of mononeuropathic pain.Eur J Pharmacol. 2018 May 15;827:41-48. doi: 10.1016/j.ejphar.2018.03.008. Epub 2018 Mar 8.
18	8-methoxypsoralen reduces AKT phosphorylation, induces intrinsic and extrinsic apoptotic pathways, and suppresses cell growth of SK-N-AS neuroblastoma and SW620 metastatic colon cancer cells.J Ethnopharmacol. 2017 Jul 31;207:19-29. doi: 10.1016/j.jep.2017.06.010. Epub 2017 Jun 13.
19	Contributions of the Melanopsin-Expressing Ganglion Cells, Cones, and Rods to the Pupillary Light Response in Obstructive Sleep Apnea.Invest Ophthalmol Vis Sci. 2019 Jul 1;60(8):3002-3012. doi: 10.1167/iovs.19-26944.
20	Morphine-dependent and abstinent mice are characterized by a broader distribution of the neurons co-expressing mu and delta opioid receptors.Neuropharmacology. 2019 Jul 1;152:30-41. doi: 10.1016/j.neuropharm.2019.03.009. Epub 2019 Mar 8.
21	Case report of myeloperoxidase deficiency associated with disseminated paracoccidioidomycosis and peritoneal tuberculosis.Rev Soc Bras Med Trop. 2017 Jul-Aug;50(4):568-570. doi: 10.1590/0037-8682-0462-2016.
22	Degeneration of human photosensitive retinal ganglion cells may explain sleep and circadian rhythms disorders in Parkinson's disease.Acta Neuropathol Commun. 2018 Sep 10;6(1):90. doi: 10.1186/s40478-018-0596-z.
23	Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.PLoS One. 2016 Apr 15;11(4):e0152670. doi: 10.1371/journal.pone.0152670. eCollection 2016.
24	Adaptive homeostasis of the vitamin D-vitamin D nuclear receptor axis in 8-methoxypsoralen-induced hepatotoxicity. Toxicol Appl Pharmacol. 2019 Jan 1;362:150-158. doi: 10.1016/j.taap.2018.11.002. Epub 2018 Nov 10.
25	Cannabinoid-mediated retinal rescue correlates with improved circadian parameters in retinal dystrophic rats.Exp Eye Res. 2019 Mar;180:192-199. doi: 10.1016/j.exer.2018.12.022. Epub 2018 Dec 31.
26	Synthesis and in vitro biological evaluation of novel coumarin derivatives containing isoxazole moieties on melanin synthesis in B16 cells and inhibition on bacteria.Bioorg Med Chem Lett. 2017 Jun 15;27(12):2674-2677. doi: 10.1016/j.bmcl.2017.04.039. Epub 2017 Apr 14.
27	Extracorporeal photochemotherapy induces bona fide immunogenic cell death.Cell Death Dis. 2019 Aug 2;10(8):578. doi: 10.1038/s41419-019-1819-3.
28	Mu (mu) opioid receptor regulation of ethanol-induced dopamine response in the ventral striatum: evidence of genotype specific sexual dimorphic epistasis.Biol Psychiatry. 2007 Sep 15;62(6):627-34. doi: 10.1016/j.biopsych.2006.11.016. Epub 2007 Mar 6.
29	An alternative for extracorporeal photopheresis: 8-methoxypsoralen and UVA-treated leucocytes from allogeneic donors improve graft-versus-host disease in mice.Vox Sang. 2018 Nov;113(8):803-810. doi: 10.1111/vox.12723. Epub 2018 Oct 23.
30	HapMap-based study on the association between MPO and GSTP1 gene polymorphisms and lung cancer susceptibility in Chinese Han population.Acta Pharmacol Sin. 2014 May;35(5):636-44. doi: 10.1038/aps.2014.11.
31	Down regulation of differentiated embryonic chondrocytes 1 (DEC1) is involved in 8-methoxypsoralen-induced apoptosis in HepG2 cells. Toxicology. 2012 Nov 15;301(1-3):58-65. doi: 10.1016/j.tox.2012.06.022. Epub 2012 Jul 11.
32	Choroideremia: melanopsin-mediated postillumination pupil relaxation is abnormally slow.Acta Ophthalmol. 2017 Dec;95(8):809-814. doi: 10.1111/aos.13394. Epub 2017 Mar 8.
33	Shared and Differential Retinal Responses against Optic Nerve Injury and Ocular Hypertension.Front Neurosci. 2017 Apr 26;11:235. doi: 10.3389/fnins.2017.00235. eCollection 2017.
34	Functional characterisation of naturally occurring mutations in human melanopsin.Cell Mol Life Sci. 2018 Oct;75(19):3609-3624. doi: 10.1007/s00018-018-2813-0. Epub 2018 Apr 26.
35	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.
36	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.
37	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.