Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL0Z8E6)

• DOT Name: Beta-crystallin B2 (CRYBB2)
• Synonyms: Beta-B2 crystallin; Beta-crystallin Bp
• Gene Name: CRYBB2
• Related Disease:
  Cataract 2, multiple types
  Cataract 3 multiple types
  Age-related macular degeneration
  Autoimmune disease
  Blindness
  Cataract
  Cataract 9 multiple types
  Early-onset posterior polar cataract
  Microphthalmia
  Neoplasm
  Schizophrenia
  Uveitis
  Cataract - microcornea syndrome
  Cerulean cataract
  Early-onset nuclear cataract
  Early-onset posterior subcapsular cataract
  Early-onset sutural cataract
  Pulverulent cataract
  Total early-onset cataract
  Congenital contractural arachnodactyly
  Glaucoma/ocular hypertension
  Malignant rhabdoid tumour
  Neurofibromatosis type 2
  Prostate cancer
  Prostate carcinoma
• UniProt ID: CRBB2_HUMAN
• PDB ID: 1YTQ; 7K7U
• Pfam ID: PF00030
• Sequence:
  MASDHQTQAGKPQSLNPKIIIFEQENFQGHSHELNGPCPNLKETGVEKAGSVLVQAGPWV
  GYEQANCKGEQFVFEKGEYPRWDSWTSSRRTDSLSSLRPIKVDSQEHKIILYENPNFTGK
  KMEIIDDDVPSFHAHGYQEKVSSVRVQSGTWVGYQYPGYRGLQYLLEKGDYKDSSDFGAP
  HPQVQSVRRIRDMQWHQRGAFHPSN
• Function: Crystallins are the dominant structural components of the vertebrate eye lens.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cataract 2, multiple types	DISF9EJ8	Definitive	Autosomal dominant	[1]
Cataract 3 multiple types	DIS6WOLW	Definitive	Autosomal dominant	[2]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Blindness	DISTIM10	Strong	Genetic Variation	[3]
Cataract	DISUD7SL	Strong	Genetic Variation	[5]
Cataract 9 multiple types	DIS9JQ8P	Strong	Genetic Variation	[6]
Early-onset posterior polar cataract	DISJFK9W	Strong	Genetic Variation	[7]
Microphthalmia	DISGEBES	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[5]
Uveitis	DISV0RYS	Strong	Biomarker	[4]
Cataract - microcornea syndrome	DISL51AQ	Supportive	Autosomal dominant	[10]
Cerulean cataract	DIS5D1OI	Supportive	Autosomal dominant	[11]
Early-onset nuclear cataract	DISGIHUY	Supportive	Autosomal dominant	[12]
Early-onset posterior subcapsular cataract	DISB7SJS	Supportive	Autosomal dominant	[7]
Early-onset sutural cataract	DISKFS14	Supportive	Autosomal dominant	[13]
Pulverulent cataract	DISMJ2AH	Supportive	Autosomal dominant	[14]
Total early-onset cataract	DISACMEZ	Supportive	Autosomal dominant	[15]
Congenital contractural arachnodactyly	DISOM1K7	Limited	Biomarker	[16]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[17]
Malignant rhabdoid tumour	DIS46HZU	Limited	Genetic Variation	[18]
Neurofibromatosis type 2	DISI8ECS	Limited	Biomarker	[19]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[9]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Beta-crystallin B2 (CRYBB2).	[20]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Beta-crystallin B2 (CRYBB2).	[21]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Beta-crystallin B2 (CRYBB2).	[22]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Beta-crystallin B2 (CRYBB2).	[24]

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 increases the methylation of Beta-crystallin B2 (CRYBB2).	[23]

References

• [1] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [2] A second gene for cerulean cataracts maps to the beta crystallin region on chromosome 22. Genomics. 1996 Aug 1;35(3):539-42. doi: 10.1006/geno.1996.0395.
• [3] Mutation screen of beta-crystallin genes in 274 patients with age-related macular degeneration.Ophthalmic Genet. 2010 Sep;31(3):129-34. doi: 10.3109/13816810.2010.486774.
• [4] Posttranslational modification of differentially expressed mitochondrial proteins in the retina during early experimental autoimmune uveitis.Mol Vis. 2011;17:1814-21. Epub 2011 Jul 6.
• [5] Crybb2 Mutations Consistently Affect Schizophrenia Endophenotypes in Mice.Mol Neurobiol. 2019 Jun;56(6):4215-4230. doi: 10.1007/s12035-018-1365-5. Epub 2018 Oct 6.
• [6] A CRYBB2 mutation in a Taiwanese family with autosomal dominant cataract.J Formos Med Assoc. 2019 Jan;118(1 Pt 1):57-63. doi: 10.1016/j.jfma.2018.01.005. Epub 2018 Feb 12.
• [7] Characterization of a novel mutation in the CRYBB2 gene associated with autosomal dominant congenital posterior subcapsular cataract in a Chinese family. Mol Vis. 2011 Jan 13;17:144-52.
• [8] 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.
• [9] Analyzing the Association of Polymorphisms in the CRYBB2 Gene with Prostate Cancer Risk in African Americans.Anticancer Res. 2015 May;35(5):2565-70.
• [10] Novel beta-crystallin gene mutations in Chinese families with nuclear cataracts. Arch Ophthalmol. 2011 Mar;129(3):337-43. doi: 10.1001/archophthalmol.2011.11.
• [11] Autosomal dominant cerulean cataract is associated with a chain termination mutation in the human beta-crystallin gene CRYBB2. Hum Mol Genet. 1997 May;6(5):665-8. doi: 10.1093/hmg/6.5.665.
• [12] Mutation analysis of congenital cataract in a Basotho family identified a new missense allele in CRYBB2. Mol Vis. 2009 Jul 30;15:1470-5.
• [13] A unique form of autosomal dominant cataract explained by gene conversion between beta-crystallin B2 and its pseudogene. J Med Genet. 2001 Jun;38(6):392-6. doi: 10.1136/jmg.38.6.392.
• [14] Genetic heterogeneity of the Coppock-like cataract: a mutation in CRYBB2 on chromosome 22q11.2. Invest Ophthalmol Vis Sci. 2000 Jan;41(1):159-65.
• [15] Molecular analysis of cataract families in India: new mutations in the CRYBB2 and GJA3 genes and rare polymorphisms. Mol Vis. 2010 Sep 10;16:1837-47.
• [16] JQ1 Induces DNA Damage and Apoptosis, and Inhibits Tumor Growth in a Patient-Derived Xenograft Model of Cholangiocarcinoma.Mol Cancer Ther. 2018 Jan;17(1):107-118. doi: 10.1158/1535-7163.MCT-16-0922. Epub 2017 Nov 15.
• [17] Intravitreal injection of -crystallin B2 improves retinal ganglion cell survival in an experimental animal model of glaucoma.PLoS One. 2017 Apr 6;12(4):e0175451. doi: 10.1371/journal.pone.0175451. eCollection 2017.
• [18] The t(11;22)(p15.5;q11.23) in a retroperitoneal rhabdoid tumor also includes a regional deletion distal to CRYBB2 on 22q.Genes Chromosomes Cancer. 1995 Jul;13(3):145-50. doi: 10.1002/gcc.2870130302.
• [19] Neurofibromatosis type 2 appears to be a genetically homogeneous disease.Am J Hum Genet. 1992 Sep;51(3):486-96.
• [20] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [21] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [22] Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
• [23] 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.
• [24] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.