Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8617WJ)

• DOT Name: Beta-crystallin A3 (CRYBA1)
• Gene Name: CRYBA1
• Related Disease:
  Cataract 10 multiple types
  Persistent hyperplastic primary vitreous
  Disorder of orbital region
  Major depressive disorder
  Neurofibromatosis type 1
  Ocular hypertension
  Promyelocytic leukaemia
  Early-onset lamellar cataract
  Early-onset nuclear cataract
  Early-onset posterior polar cataract
  Early-onset sutural cataract
  Melanoma
  Cataract
• UniProt ID: CRBA1_HUMAN
• Pfam ID: PF00030
• Sequence:
  METQAEQQELETLPTTKMAQTNPTPGSLGPWKITIYDQENFQGKRMEFTSSCPNVSERSF
  DNVRSLKVESGAWIGYEHTSFCGQQFILERGEYPRWDAWSGSNAYHIERLMSFRPICSAN
  HKESKMTIFEKENFIGRQWEISDDYPSLQAMGWFNNEVGSMKIQSGAWVCYQYPGYRGYQ
  YILECDHHGGDYKHWREWGSHAQTSQIQSIRRIQQ
• Function: Crystallins are the dominant structural components of the vertebrate eye lens.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cataract 10 multiple types	DISJOCKU	Definitive	Autosomal dominant	[1]
Persistent hyperplastic primary vitreous	DISABPH6	Definitive	Biomarker	[2]
Disorder of orbital region	DISH0ECJ	Strong	Genetic Variation	[3]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[4]
Neurofibromatosis type 1	DIS53JH9	Strong	Biomarker	[5]
Ocular hypertension	DISC2BT9	moderate	Biomarker	[6]
Promyelocytic leukaemia	DISYGG13	moderate	Biomarker	[7]
Early-onset lamellar cataract	DISR7WXX	Supportive	Autosomal dominant	[8]
Early-onset nuclear cataract	DISGIHUY	Supportive	Autosomal dominant	[9]
Early-onset posterior polar cataract	DISJFK9W	Supportive	Autosomal dominant	[10]
Early-onset sutural cataract	DISKFS14	Supportive	Autosomal dominant	[11]
Melanoma	DIS1RRCY	Disputed	Genetic Variation	[12]
Cataract	DISUD7SL	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Beta-crystallin A3 (CRYBA1).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Beta-crystallin A3 (CRYBA1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Beta-crystallin A3 (CRYBA1).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Beta-crystallin A3 (CRYBA1).	[17]

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 decreases the methylation of Beta-crystallin A3 (CRYBA1).	[15]

References

• [1] A deletion mutation in the betaA1/A3 crystallin gene ( CRYBA1/A3) is associated with autosomal dominant congenital nuclear cataract in a Chinese family. Hum Genet. 2004 Jan;114(2):192-7. doi: 10.1007/s00439-003-1049-7. Epub 2003 Nov 4.
• [2] Modulating EGFR-MTORC1-autophagy as a potential therapy for persistent fetal vasculature (PFV) disease.Autophagy. 2020 Jun;16(6):1130-1142. doi: 10.1080/15548627.2019.1660545. Epub 2019 Sep 1.
• [3] The identification and characterization of the p.G91 deletion in CRYBA1 in a Chinese family with congenital cataracts.BMC Med Genet. 2019 Sep 5;20(1):153. doi: 10.1186/s12881-019-0882-z.
• [4] Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.Nat Genet. 2018 May;50(5):668-681. doi: 10.1038/s41588-018-0090-3. Epub 2018 Apr 26.
• [5] Physical mapping of the von Recklinghausen neurofibromatosis region on chromosome 17.Am J Hum Genet. 1989 Jan;44(1):58-67.
• [6] Retinal gene profiling in a hereditary rodent model of elevated intraocular pressure.Mol Vis. 2006 Oct 18;12:1199-210.
• [7] Precise localization of NF1 to 17q11.2 by balanced translocation.Am J Hum Genet. 1989 Jan;44(1):20-4.
• [8] Characterization of the G91del CRYBA1/3-crystallin protein: a cause of human inherited cataract. Hum Mol Genet. 2004 May 1;13(9):945-53. doi: 10.1093/hmg/ddh110. Epub 2004 Mar 11.
• [9] A recurrent mutation in CRYBA1 is associated with an autosomal dominant congenital nuclear cataract disease in a Chinese family. Mol Vis. 2011;17:1559-63. Epub 2011 Jun 9.
• [10] A splice site mutation in CRYBA1/A3 causing autosomal dominant posterior polar cataract in a Chinese pedigree. Mol Vis. 2010 Feb 5;16:154-60.
• [11] Autosomal dominant zonular cataract with sutural opacities is associated with a splice mutation in the betaA3/A1-crystallin gene. Mol Vis. 1998 Oct 23;4:21.
• [12] A Role for A3/A1-Crystallin in Type 2 EMT of RPE Cells Occurring in Dry Age-Related Macular Degeneration.Invest Ophthalmol Vis Sci. 2018 Mar 20;59(4):AMD104-AMD113. doi: 10.1167/iovs.18-24132.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.