Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQJ5XGE)

• DOT Name: Beta-crystallin A4 (CRYBA4)
• Synonyms: Beta-A4 crystallin
• Gene Name: CRYBA4
• Related Disease:
  Microphthalmia
  Cataract 23
  Cataract - microcornea syndrome
  Early-onset lamellar cataract
  Clear cell renal carcinoma
• UniProt ID: CRBA4_HUMAN
• PDB ID: 3LWK
• Pfam ID: PF00030
• Sequence:
  MTLQCTKSAGPWKMVVWDEDGFQGRRHEFTAECPSVLELGFETVRSLKVLSGAWVGFEHA
  GFQGQQYILERGEYPSWDAWGGNTAYPAERLTSFRPAACANHRDSRLTIFEQENFLGKKG
  ELSDDYPSLQAMGWEGNEVGSFHVHSGAWVCSQFPGYRGFQYVLECDHHSGDYKHFREWG
  SHAPTFQVQSIRRIQQ
• Function: Crystallins are the dominant structural components of the vertebrate eye lens.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Microphthalmia	DISGEBES	Definitive	Genetic Variation	[1]
Cataract 23	DISXCZSQ	Strong	Autosomal dominant	[2]
Cataract - microcornea syndrome	DISL51AQ	Supportive	Autosomal dominant	[3]
Early-onset lamellar cataract	DISR7WXX	Supportive	Autosomal dominant	[2]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[4]

2 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 A4 (CRYBA4).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Beta-crystallin A4 (CRYBA4).	[8]

4 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 Beta-crystallin A4 (CRYBA4).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Beta-crystallin A4 (CRYBA4).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Beta-crystallin A4 (CRYBA4).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Beta-crystallin A4 (CRYBA4).	[9]

References

• [1] A genome-wide linkage scan in Tunisian families identifies a novel locus for non-syndromic posterior microphthalmia to chromosome 2q37.1.Hum Genet. 2009 Oct;126(4):575-87. doi: 10.1007/s00439-009-0688-8. Epub 2009 Jun 14.
• [2] CRYBA4, a novel human cataract gene, is also involved in microphthalmia. Am J Hum Genet. 2006 Oct;79(4):702-9. doi: 10.1086/507712. Epub 2006 Aug 17.
• [3] A missense mutation in CRYBA4 associated with congenital cataract and microcornea. Mol Vis. 2010 Jun 5;16:1019-24.
• [4] IDUA, NDST1, SAP30L, CRYBA4, and SI as novel prognostic signatures clear cell renal cell carcinoma.J Cell Physiol. 2019 Sep;234(9):16320-16327. doi: 10.1002/jcp.28297. Epub 2019 Feb 28.
• [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] 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.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] 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.
• [9] 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.