Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3QREFR)

• DOT Name: Phakinin (BFSP2)
• Synonyms: 49 kDa cytoskeletal protein; Beaded filament structural protein 2; Lens fiber cell beaded filament protein CP 47; CP47; Lens fiber cell beaded filament protein CP 49; CP49; Lens intermediate filament-like light; LIFL-L
• Gene Name: BFSP2
• Related Disease:
  Cataract 12 multiple types
  Cataract 9 multiple types
  Myopia
  Cataract
  Cowden disease
  Thrombocytopenia 1
  Cataract 5 multiple types
  Neoplasm
  Rhabdomyosarcoma
  Early-onset lamellar cataract
  Early-onset sutural cataract
  Pulverulent cataract
  Microphthalmia
• UniProt ID: BFSP2_HUMAN
• Pfam ID: PF00038
• Sequence:
  MSERRVVVDLPTSASSSMPLQRRRASFRGPRSSSSLESPPASRTNAMSGLVRAPGVYVGT
  APSGCIGGLGARVTRRALGISSVFLQGLRSSGLATVPAPGLERDHGAVEDLGGCLVEYMA
  KVHALEQVSQELETQLRMHLESKATRSGNWGALRASWASSCQQVGEAVLENARLMLQTET
  IQAGADDFKERYENEQPFRKAAEEEINSLYKVIDEANLTKMDLESQIESLKEELGSLSRN
  YEEDVKLLHKQLAGCELEQMDAPIGTGLDDILETIRIQWERDVEKNRVEAGALLQAKQQA
  EVAHMSQTQEEKLAAALRVELHNTSCQVQSLQAETESLRALKRGLENTLHDAKHWHDMEL
  QNLGAVVGRLEAELREIRAEAEQQQQERAHLLARKCQLQKDVASYHALLDREESG
• Function: Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA. Plays a role in maintenance of retinal lens optical clarity.
• Tissue Specificity: 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 12 multiple types	DISCB1CW	Definitive	Autosomal dominant	[1]
Cataract 9 multiple types	DIS9JQ8P	Definitive	Genetic Variation	[2]
Myopia	DISK5S60	Definitive	Genetic Variation	[3]
Cataract	DISUD7SL	Strong	Genetic Variation	[4]
Cowden disease	DISMYKCE	Strong	Biomarker	[5]
Thrombocytopenia 1	DISTC3AW	Strong	Biomarker	[6]
Cataract 5 multiple types	DIS4AZEB	moderate	Genetic Variation	[7]
Neoplasm	DISZKGEW	moderate	Biomarker	[8]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[8]
Early-onset lamellar cataract	DISR7WXX	Supportive	Autosomal dominant	[9]
Early-onset sutural cataract	DISKFS14	Supportive	Autosomal dominant	[10]
Pulverulent cataract	DISMJ2AH	Supportive	Autosomal dominant	[4]
Microphthalmia	DISGEBES	Limited	Genetic Variation	[11]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Phakinin (BFSP2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Phakinin (BFSP2).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Phakinin (BFSP2).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Phakinin (BFSP2).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Phakinin (BFSP2).	[14]

References

• [1] A new locus for autosomal dominant congenital cataracts maps to chromosome 3. Invest Ophthalmol Vis Sci. 2000 Jan;41(1):36-9.
• [2] Mapping of the human CP49 gene and identification of an intragenic polymorphic marker to allow genetic linkage analysis in autosomal dominant congenital cataract.Biochem Biophys Res Commun. 2000 Apr 13;270(2):432-6. doi: 10.1006/bbrc.2000.2442.
• [3] Clinical description and genome wide linkage study of Y-sutural cataract and myopia in a Chinese family.Mol Vis. 2004 Nov 17;10:890-900.
• [4] A novel p.G112E mutation in BFSP2 associated with autosomal dominant pulverulent cataract with sutural opacities. Curr Eye Res. 2014 Oct;39(10):1013-9. doi: 10.3109/02713683.2014.891749. Epub 2014 Mar 21.
• [5] Combined effects of NaCl and Cd(2+) stress on the photosynthetic apparatus of Thellungiella salsuginea.Biochim Biophys Acta Bioenerg. 2018 Dec;1859(12):1274-1287. doi: 10.1016/j.bbabio.2018.10.001. Epub 2018 Oct 18.
• [6] Apparent Affinity Estimates and Reversal of the Effects of Synthetic Cannabinoids AM-2201, CP-47,497, JWH-122, and JWH-250 by Rimonabant in Rhesus Monkeys.J Pharmacol Exp Ther. 2017 Aug;362(2):278-286. doi: 10.1124/jpet.117.240572. Epub 2017 May 22.
• [7] A new mutation in BFSP2 (G1091A) causes autosomal dominant congenital lamellar cataracts.Mol Vis. 2008;14:1906-11. Epub 2008 Oct 24.
• [8] Rhabdomyosarcoma and Wilms tumors contain a subpopulation of noggin producing, myogenic cells immunoreactive for lens beaded filament proteins.PLoS One. 2019 Apr 11;14(4):e0214758. doi: 10.1371/journal.pone.0214758. eCollection 2019.
• [9] A juvenile-onset, progressive cataract locus on chromosome 3q21-q22 is associated with a missense mutation in the beaded filament structural protein-2. Am J Hum Genet. 2000 Apr;66(4):1426-31. doi: 10.1086/302871. Epub 2000 Mar 22.
• [10] Progressive sutural cataract associated with a BFSP2 mutation in a Chinese family. Mol Vis. 2006 Dec 20;12:1626-31.
• [11] Novel recessive BFSP2 and PITX3 mutations: insights into mutational mechanisms from consanguineous populations.Genet Med. 2011 Nov;13(11):978-81. doi: 10.1097/GIM.0b013e31822623d5.
• [12] 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.
• [13] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [14] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.