Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEW1ZM5)

• DOT Name: Retinoschisin (RS1)
• Synonyms: X-linked juvenile retinoschisis protein
• Gene Name: RS1
• Related Disease: X-linked retinoschisis
• UniProt ID: XLRS1_HUMAN
• PDB ID: 3JD6; 5N6W
• Pfam ID: PF00754
• Sequence:
  MSRKIEGFLLLLLFGYEATLGLSSTEDEGEDPWYQKACKCDCQGGPNALWSAGATSLDCI
  PECPYHKPLGFESGEVTPDQITCSNPEQYVGWYSSWTANKARLNSQGFGCAWLSKFQDSS
  QWLQIDLKEIKVISGILTQGRCDIDEWMTKYSVQYRTDERLNWIYYKDQTGNNRVFYGNS
  DRTSTVQNLLRPPIISRFIRLIPLGWHVRIAIRMELLECVSKCA
• Function: Binds negatively charged membrane lipids, such as phosphatidylserine and phosphoinositides. May play a role in cell-cell adhesion processes in the retina, via homomeric interaction between octamers present on the surface of two neighboring cells. Required for normal structure and function of the retina.
• Tissue Specificity: Restricted to the retina (at protein level) . Detected in the inner segment of the photoreceptors, the inner nuclear layer, the inner plexiform layer and the ganglion cell layer (at protein level). At the macula, expressed in both the outer and inner nuclear layers and in the inner plexiform layer (at protein level) . Detected in retina . Detected only within the photoreceptor cell layer, most prominently within the inner segments of the photoreceptors . Undetectable in the inner plexiform layers and the inner nuclear layer .

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
X-linked retinoschisis	DISKV7Y8	Definitive	X-linked	[1]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the secretion of Retinoschisin (RS1).	[2]
Ximelegatran	DMU8ANS	Approved	Ximelegatran increases the secretion of Retinoschisin (RS1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Malathion	DMXZ84M	Approved	Malathion increases the expression of Retinoschisin (RS1).	[3]

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 affects the methylation of Retinoschisin (RS1).	[4]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Regulation of retinoschisin secretion in Weri-Rb1 cells by the F-actin and microtubule cytoskeleton. PLoS One. 2011;6(6):e20707. doi: 10.1371/journal.pone.0020707. Epub 2011 Jun 27.
• [3] 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.
• [4] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.