Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK7R6HC)

• DOT Name: Lens fiber membrane intrinsic protein (LIM2)
• Synonyms: MP18; MP19; MP20
• Gene Name: LIM2
• Related Disease:
  Cataract 19 multiple types
  Lymphatic malformation 1
  Cataract 20 multiple types
  Glioma
  Cataract
  Total early-onset cataract
  Adult respiratory distress syndrome
  Microphthalmia
  Reducing body myopathy
• UniProt ID: LMIP_HUMAN
• Pfam ID: PF00822
• Sequence:
  MYSFMGGGLFCAWVGTILLVVAMATDHWMQYRLSGSFAHQGLWRYCLGNKCYLQTDSIAY
  WNATRAFMILSALCAISGIIMGIMAFAHQPTFSRISRPFSAGIMFFSSTLFVVLALAIYT
  GVTVSFLGRRFGDWRFSWSYILGWVAVLMTFFAGIFYMCAYRVHECRRLSTPR
• Function: Present in the thicker 16-17 nm junctions of mammalian lens fiber cells, where it may contribute to cell junctional organization. Acts as a receptor for calmodulin. May play an important role in both lens development and cataractogenesis.
• Tissue Specificity: Eye lens specific.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cataract 19 multiple types	DISHHVZB	Definitive	Autosomal recessive	[1]
Lymphatic malformation 1	DIS857QZ	Definitive	Biomarker	[2]
Cataract 20 multiple types	DISN0IHS	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Cataract	DISUD7SL	moderate	Biomarker	[1]
Total early-onset cataract	DISACMEZ	Supportive	Autosomal dominant	[1]
Adult respiratory distress syndrome	DISIJV47	Limited	Biomarker	[5]
Microphthalmia	DISGEBES	Limited	Biomarker	[6]
Reducing body myopathy	DISFDWS0	Limited	Genetic Variation	[7]

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 Lens fiber membrane intrinsic protein (LIM2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Lens fiber membrane intrinsic protein (LIM2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Lens fiber membrane intrinsic protein (LIM2).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Lens fiber membrane intrinsic protein (LIM2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Lens fiber membrane intrinsic protein (LIM2).	[12]

References

• [1] A missense mutation in LIM2 causes autosomal recessive congenital cataract. Mol Vis. 2008 Jun 23;14:1204-8.
• [2] Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics.Blood. 1999 Feb 1;93(3):1032-7.
• [3] A missense mutation in the LIM2 gene is associated with autosomal recessive presenile cataract in an inbred Iraqi Jewish family.Am J Hum Genet. 2002 May;70(5):1363-7. doi: 10.1086/340318. Epub 2002 Mar 26.
• [4] CD133 in brain tumor: the prognostic factor.Oncotarget. 2017 Feb 14;8(7):11144-11159. doi: 10.18632/oncotarget.14406.
• [5] MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome.BMC Med Genomics. 2014 Jul 28;7:46. doi: 10.1186/1755-8794-7-46.
• [6] Localization of lens intrinsic membrane protein MP19 and mutant protein MP19(To3) using fluorescent expression vectors.Mol Vis. 2002 Oct 11;8:372-88.
• [7] Familial reducing body myopathy with cytoplasmic bodies and rigid spine revisited: identification of a second LIM domain mutation in FHL1.Neuropediatrics. 2010 Feb;41(1):43-6. doi: 10.1055/s-0030-1254101. Epub 2010 Jun 22.
• [8] 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.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] 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.
• [11] 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.
• [12] 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.