Details of Drug Off-Target (DOT)

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

• DOT Name: Visual system homeobox 1
• Synonyms: Homeodomain protein RINX; Retinal inner nuclear layer homeobox protein; Transcription factor VSX1
• Gene Name: VSX1
• Related Disease:
  Posterior polymorphous corneal dystrophy
  Craniofacial anomalies and anterior segment dysgenesis syndrome
  Keratoconus 1
  Posterior polymorphous corneal dystrophy 1
• UniProt ID: VSX1_HUMAN
• Pfam ID: PF00046
• Sequence:
  MTGRDSLSDGRTSSRALVPGGSPRGSRPRGFAITDLLGLEAELPAPAGPGQGSGCEGPAV
  APCPGPGLDGSSLARGALPLGLGLLCGFGTQPPAAARAPCLLLADVPFLPPRGPEPAAPL
  APSRPPPALGRQKRSDSVSTSDEDSQSEDRNDLKASPTLGKRKKRRHRTVFTAHQLEELE
  KAFSEAHYPDVYAREMLAVKTELPEDRIQVWFQNRRAKWRKREKRWGGSSVMAEYGLYGA
  MVRHCIPLPDSVLNSAEGGLLGSCAPWLLGMHKKSMGMIRKPGSEDKLAGLWGSDHFKEG
  SSQSESGSQRGSDKVSPENGLEDVAIDLSSSARQETKKVHPGAGAQGGSNSTALEGPQPG
  KVGAT
• Function: Binds to the 37-bp core of the locus control region (LCR) of the red/green visual pigment gene cluster. May regulate the activity of the LCR and the cone opsin genes at earlier stages of development. Dispensable in early retinal development.
• Tissue Specificity: In the adult eye, expressed in lens, iris, ciliary body, choroid, optical nerve head and, most strongly, in retina, but not expressed in sclera and cornea. According to PubMed:11978762, expressed in adult retina but not in lens and cornea. Within adult retina, found exclusively in the inner nuclear layer. Isoform 1, isoform 2, isoform 3 and isoform 4 expressed in adult retina, but not in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle. Not expressed in thymus and spleen. Expressed in embryonic craniofacial tissue. Expressed in fetal (week 14) retina. Strongly expressed in neonatal retina, weakly in neonatal lens, choroid and cornea (day 1, 4; month 9).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Posterior polymorphous corneal dystrophy	DISHAYH6	Supportive	Autosomal dominant	[1]
Craniofacial anomalies and anterior segment dysgenesis syndrome	DISLU7RF	Limited	Autosomal dominant	[2]
Keratoconus 1	DISDF9F9	Limited	Autosomal dominant	[3]
Posterior polymorphous corneal dystrophy 1	DISVGA4Z	Limited	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Visual system homeobox 1.	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Visual system homeobox 1.	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Visual system homeobox 1.	[7]

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 Visual system homeobox 1.	[6]

References

• [1] VSX1: a gene for posterior polymorphous dystrophy and keratoconus. Hum Mol Genet. 2002 May 1;11(9):1029-36. doi: 10.1093/hmg/11.9.1029.
• [2] VSX1 (RINX) mutation with craniofacial anomalies, empty sella, corneal endothelial changes, and abnormal retinal and auditory bipolar cells. Ophthalmology. 2004 Apr;111(4):828-36. doi: 10.1016/j.ophtha.2003.07.006.
• [3] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.