Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF5XS0C)

• DOT Name: Gamma-crystallin S (CRYGS)
• Synonyms: Beta-crystallin S; Gamma-S-crystallin
• Gene Name: CRYGS
• Related Disease:
  Cataract 20 multiple types
  Blindness
  Cataract 5 multiple types
  Cataract 9 multiple types
  Early-onset lamellar cataract
  Early-onset sutural cataract
  Cataract
• UniProt ID: CRYGS_HUMAN
• PDB ID: 1HA4; 2M3T; 2M3U; 6FD8; 6IF9; 7N36; 7N37; 7N38; 7N39; 7N3A; 7N3B; 7NJE
• Pfam ID: PF00030
• Sequence:
  MSKTGTKITFYEDKNFQGRRYDCDCDCADFHTYLSRCNSIKVEGGTWAVYERPNFAGYMY
  ILPQGEYPEYQRWMGLNDRLSSCRAVHLPSGGQYKIQIFEKGDFSGQMYETTEDCPSIME
  QFHMREIHSCKVLEGVWIFYELPNYRGRQYLLDKKEYRKPIDWGAASPAVQSFRRIVE
• Function: Crystallins are the dominant structural components of the vertebrate eye lens.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cataract 20 multiple types	DISN0IHS	Definitive	Autosomal dominant	[1]
Blindness	DISTIM10	Strong	Biomarker	[2]
Cataract 5 multiple types	DIS4AZEB	Strong	Genetic Variation	[3]
Cataract 9 multiple types	DIS9JQ8P	Strong	Genetic Variation	[4]
Early-onset lamellar cataract	DISR7WXX	Supportive	Autosomal dominant	[5]
Early-onset sutural cataract	DISKFS14	Supportive	Autosomal dominant	[5]
Cataract	DISUD7SL	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Gamma-crystallin S (CRYGS).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Gamma-crystallin S (CRYGS).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Gamma-crystallin S (CRYGS).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Gamma-crystallin S (CRYGS).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Gamma-crystallin S (CRYGS).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Gamma-crystallin S (CRYGS).	[7]

References

• [1] Mutation analysis of 12 genes in Chinese families with congenital cataracts. Mol Vis. 2011;17:2197-206. Epub 2011 Aug 16.
• [2] Conformational dynamics study on human S-crystallin as an efficient route to childhood blindness.Biochem Biophys Res Commun. 2019 Apr 9;511(3):679-684. doi: 10.1016/j.bbrc.2019.02.124. Epub 2019 Feb 28.
• [3] Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype-Phenotype Correlations in 27 Chinese Han Families. Sci Rep. 2017 Apr 27;7(1):1219. doi: 10.1038/s41598-017-01182-9.
• [4] Novel mutation in the gamma-S crystallin gene causing autosomal dominant cataract.Mol Vis. 2009;15:476-81. Epub 2009 Mar 4.
• [5] Crystallin gene mutations in Indian families with inherited pediatric cataract. Mol Vis. 2008 Jun 16;14:1157-70.
• [6] Structure of G57W mutant of human S-crystallin and its involvement in cataract formation.J Struct Biol. 2019 Mar 1;205(3):72-78. doi: 10.1016/j.jsb.2019.02.003. Epub 2019 Feb 12.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.