Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCASGO0)

• DOT Name: Opticin (OPTC)
• Synonyms: Oculoglycan
• Gene Name: OPTC
• Related Disease:
  Neoplasm
  Age-related macular degeneration
  Cardiac failure
  Congestive heart failure
  Osteoarthritis
  Psoriasis
  Glaucoma/ocular hypertension
  Open-angle glaucoma
  OPTN-related open angle glaucoma
• UniProt ID: OPT_HUMAN
• Pfam ID: PF13855
• Sequence:
  MRLLAFLSLLALVLQETGTASLPRKERKRREEQMPREGDSFEVLPLRNDVLNPDNYGEVI
  DLSNYEELTDYGDQLPEVKVTSLAPATSISPAKSTTAPGTPSSNPTMTRPTTAGLLLSSQ
  PNHGLPTCLVCVCLGSSVYCDDIDLEDIPPLPRRTAYLYARFNRISRIRAEDFKGLTKLK
  RIDLSNNLISSIDNDAFRLLHALQDLILPENQLEALPVLPSGIEFLDVRLNRLQSSGIQP
  AAFRAMEKLQFLYLSDNLLDSIPGPLPLSLRSVHLQNNLIETMQRDVFCDPEEHKHTRRQ
  LEDIRLDGNPINLSLFPSAYFCLPRLPIGRFT
• Function: Inhibits angiogenesis in the vitreous humor of the eye, and therefore represses neovascularization. Binds collagen fibrils. May be involved in collagen fiber organization via regulation of other members of the small leucine-rich repeat proteoglycan superfamily.
• Tissue Specificity: Expressed in cartilage and synovial membranes (at protein level) . Expressed in the retina, iris, ligament, skin and fetal liver (at protein level) . Expressed in the retinal pigment epithelium (at protein level) . Expressed in synovial fibroblasts and subchondral bone osteoblasts .
• Reactome Pathway: Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[2]
Cardiac failure	DISDC067	Strong	Genetic Variation	[3]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[3]
Osteoarthritis	DIS05URM	Strong	Biomarker	[4]
Psoriasis	DIS59VMN	Strong	Biomarker	[5]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Genetic Variation	[6]
Open-angle glaucoma	DISSZEE8	Limited	Biomarker	[7]
OPTN-related open angle glaucoma	DISDR98A	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Opticin (OPTC).	[8]

2 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 Opticin (OPTC).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Opticin (OPTC).	[10]

References

• [1] A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells.Blood. 2010 Aug 12;116(6):900-8. doi: 10.1182/blood-2009-10-250209. Epub 2010 May 10.
• [2] Protein localization in the human eye and genetic screen of opticin.Hum Mol Genet. 2002 May 15;11(11):1333-42. doi: 10.1093/hmg/11.11.1333.
• [3] Optimising pacemaker therapy and medical therapy in pacemaker patients for heart failure: protocol for the OPT-PACE randomised controlled trial.BMJ Open. 2019 Jul 17;9(7):e028613. doi: 10.1136/bmjopen-2018-028613.
• [4] In vivo effect of opticin deficiency in cartilage in a surgically induced mouse model of osteoarthritis.Sci Rep. 2018 Jan 11;8(1):457. doi: 10.1038/s41598-017-18047-w.
• [5] Early clinical response to tofacitinib treatment as a predictor of subsequent efficacy: Results from two phase 3 studies of patients with moderate-to-severe plaque psoriasis.J Dermatolog Treat. 2017 Feb;28(1):3-7. doi: 10.1080/09546634.2016.1214671. Epub 2016 Aug 18.
• [6] Role of CYP1B1, MYOC, OPTN, and OPTC genes in adult-onset primary open-angle glaucoma: predominance of CYP1B1 mutations in Indian patients.Mol Vis. 2007 Apr 30;13:667-76.
• [7] Evaluation of the OPTC gene in primary open angle glaucoma: functional significance of a silent change.BMC Mol Biol. 2007 Mar 14;8:21. doi: 10.1186/1471-2199-8-21.
• [8] 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.
• [9] 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.
• [10] 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.