Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDI4W3V)

• DOT Name: Beta-crystallin B1 (CRYBB1)
• Synonyms: Beta-B1 crystallin
• Gene Name: CRYBB1
• Related Disease:
  Cataract 17 multiple types
  Cataract - microcornea syndrome
  Early-onset nuclear cataract
  Pulverulent cataract
• UniProt ID: CRBB1_HUMAN
• PDB ID: 1OKI
• Pfam ID: PF00030
• Sequence:
  MSQAAKASASATVAVNPGPDTKGKGAPPAGTSPSPGTTLAPTTVPITSAKAAELPPGNYR
  LVVFELENFQGRRAEFSGECSNLADRGFDRVRSIIVSAGPWVAFEQSNFRGEMFILEKGE
  YPRWNTWSSSYRSDRLMSFRPIKMDAQEHKISLFEGANFKGNTIEIQGDDAPSLWVYGFS
  DRVGSVKVSSGTWVGYQYPGYRGYQYLLEPGDFRHWNEWGAFQPQMQSLRRLRDKQWHLE
  GSFPVLATEPPK
• Function: Crystallins are the dominant structural components of the vertebrate eye lens.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cataract 17 multiple types	DIS85JDX	Definitive	Autosomal dominant	[1]
Cataract - microcornea syndrome	DISL51AQ	Supportive	Autosomal dominant	[2]
Early-onset nuclear cataract	DISGIHUY	Supportive	Autosomal dominant	[3]
Pulverulent cataract	DISMJ2AH	Supportive	Autosomal dominant	[4]

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 Beta-crystallin B1 (CRYBB1).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Beta-crystallin B1 (CRYBB1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Beta-crystallin B1 (CRYBB1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Beta-crystallin B1 (CRYBB1).	[7]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Beta-crystallin B1 (CRYBB1).	[8]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Beta-crystallin B1 (CRYBB1).	[9]

References

• [1] A nonsense mutation in CRYBB1 associated with autosomal dominant cataract linked to human chromosome 22q. Am J Hum Genet. 2002 Nov;71(5):1216-21. doi: 10.1086/344212. Epub 2002 Oct 1.
• [2] CRYBB1 mutation associated with congenital cataract and microcornea. Mol Vis. 2005 Aug 8;11:587-93.
• [3] A novel nonsense mutation in CRYBB1 associated with autosomal dominant congenital cataract. Mol Vis. 2008 Apr 18;14:727-31.
• [4] Clinical and molecular analysis of children with central pulverulent cataract from the Arabian Peninsula. Br J Ophthalmol. 2012 May;96(5):650-5. doi: 10.1136/bjophthalmol-2011-301053. Epub 2012 Jan 19.
• [5] 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.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [9] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [10] 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.