Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDLY6TC)

• DOT Name: LIM domain only protein 7 (LMO7)
• Synonyms: LMO-7; F-box only protein 20; LOMP
• Gene Name: LMO7
• Related Disease:
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Emery-Dreifuss muscular dystrophy
  Lung cancer
  Lung carcinoma
  Myopathy
  Neoplasm
  Non-small-cell lung cancer
  Open-angle glaucoma
  Retinoblastoma
  Type-1 diabetes
  Vascular disease
  Bipolar disorder
  Schizoaffective disorder
  Schizophrenia
  Thyroid gland papillary carcinoma
  Diabetic retinopathy
• UniProt ID: LMO7_HUMAN
• PDB ID: 2EAQ
• Pfam ID: PF00307 ; PF15949 ; PF00412 ; PF00595
• Sequence:
  MKKIRICHIFTFYSWMSYDVLFQRTELGALEIWRQLICAHVCICVGWLYLRDRVCSKKDI
  ILRTEQNSGRTILIKAVTEKNFETKDFRASLENGVLLCDLINKLKPGVIKKINRLSTPIA
  GLDNINVFLKACEQIGLKEAQLFHPGDLQDLSNRVTVKQEETDRRVKNVLITLYWLGRKA
  QSNPYYNGPHLNLKAFENLLGQALTKALEDSSFLKRSGRDSGYGDIWCPERGEFLAPPRH
  HKREDSFESLDSLGSRSLTSCSSDITLRGGREGFESDTDSEFTFKMQDYNKDDMSYRRIS
  AVEPKTALPFNRFLPNKSRQPSYVPAPLRKKKPDKHEDNRRSWASPVYTEADGTFSSNQR
  RIWGTNVENWPTVQGTSKSSCYLEEEKAKTRSIPNIVKDDLYVRKLSPVMPNPGNAFDQF
  LPKCWTPEDVNWKRIKRETYKPWYKEFQGFSQFLLLQALQTYSDDILSSETHTKIDPTSG
  PRLITRRKNLSYAPGYRRDDLEMAALDPDLENDDFFVRKTGVFHANPYVLRAFEDFRKFS
  EQDDSVERDIILQCREGELVLPDLEKDDMIVRRIPAQKKEVPLSGAPDRYHPVPFPEPWT
  LPPEIQAKFLCVFERTCPSKEKSNSCRILVPSYRQKKDDMLTRKIQSWKLGTTVPPISFT
  PGPCSEADLKRWEAIREASRLRHKKRLMVERLFQKIYGENGSKSMSDVSAEDVQNLRQLR
  YEEMQKIKSQLKEQDQKWQDDLAKWKDRRKSYTSDLQKKKEEREEIEKQALEKSKRSSKT
  FKEMLQDRESQNQKSTVPSRRRMYSFDDVLEEGKRPPTMTVSEASYQSERVEEKGATYPS
  EIPKEDSTTFAKREDRVTTEIQLPSQSPVEEQSPASLSSLRSRSTQMESTRVSASLPRSY
  RKTDTVRLTSVVTPRPFGSQTRGISSLPRSYTMDDAWKYNGDVEDIKRTPNNVVSTPAPS
  PDASQLASSLSSQKEVAATEEDVTRLPSPTSPFSSLSQDQAATSKATLSSTSGLDLMSES
  GEGEISPQREVSRSQDQFSDMRISINQTPGKSLDFGFTIKWDIPGIFVASVEAGSPAEFS
  QLQVDDEIIAINNTKFSYNDSKEWEEAMAKAQETGHLVMDVRRYGKAGSPETKWIDATSG
  IYNSEKSSNLSVTTDFSESLQSSNIESKEINGIHDESNAFESKASESISLKNLKRRSQFF
  EQGSSDSVVPDLPVPTISAPSRWVWDQEEERKRQERWQKEQDRLLQEKYQREQEKLREEW
  QRAKQEAERENSKYLDEELMVLSSNSMSLTTREPSLATWEATWSEGSKSSDREGTRAGEE
  ERRQPQEEVVHEDQGKKPQDQLVIERERKWEQQLQEEQEQKRLQAEAEEQKRPAEEQKRQ
  AEIERETSVRIYQYRRPVDSYDIPKTEEASSGFLPGDRNKSRSTTELDDYSTNKNGNNKY
  LDQIGNMTSSQRRSKKEQVPSGAELERQQILQEMRKRTPLHNDNSWIRQRSASVNKEPVS
  LPGIMRRGESLDNLDSPRSNSWRQPPWLNQPTGFYASSSVQDFSRPPPQLVSTSNRAYMR
  NPSSSVPPPSAGSVKTSTTGVATTQSPTPRSHSPSASQSGSQLRNRSVSGKRICSYCNNI
  LGKGAAMIIESLGLCYHLHCFKCVACECDLGGSSSGAEVRIRNHQLYCNDCYLRFKSGRP
  TAM
• Tissue Specificity: Widely expressed. Isoform 2 and isoform 4 are predominantly expressed in brain.
• KEGG Pathway: Adherens junction (hsa04520)
• Reactome Pathway:
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dilated cardiomyopathy	DISX608J	Strong	Biomarker	[1]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[1]
Emery-Dreifuss muscular dystrophy	DISYTPR5	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Myopathy	DISOWG27	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[3]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[6]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[7]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[8]
Vascular disease	DISVS67S	Strong	Biomarker	[9]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[10]
Schizoaffective disorder	DISLBW6B	moderate	Genetic Variation	[10]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[10]
Thyroid gland papillary carcinoma	DIS48YMM	Disputed	Genetic Variation	[11]
Diabetic retinopathy	DISHGUJM	Limited	Genetic Variation	[12]

6 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 LIM domain only protein 7 (LMO7).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of LIM domain only protein 7 (LMO7).	[26]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of LIM domain only protein 7 (LMO7).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of LIM domain only protein 7 (LMO7).	[30]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of LIM domain only protein 7 (LMO7).	[28]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of LIM domain only protein 7 (LMO7).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of LIM domain only protein 7 (LMO7).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of LIM domain only protein 7 (LMO7).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of LIM domain only protein 7 (LMO7).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of LIM domain only protein 7 (LMO7).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of LIM domain only protein 7 (LMO7).	[18]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of LIM domain only protein 7 (LMO7).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of LIM domain only protein 7 (LMO7).	[20]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of LIM domain only protein 7 (LMO7).	[21]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of LIM domain only protein 7 (LMO7).	[22]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of LIM domain only protein 7 (LMO7).	[23]
Aspirin	DM672AH	Approved	Aspirin increases the expression of LIM domain only protein 7 (LMO7).	[24]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of LIM domain only protein 7 (LMO7).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of LIM domain only protein 7 (LMO7).	[27]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of LIM domain only protein 7 (LMO7).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of LIM domain only protein 7 (LMO7).	[31]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of LIM domain only protein 7 (LMO7).	[32]

References

• [1] Association of LIM Domain 7 Gene Polymorphisms and Plasma Levels of LIM Domain 7 with Dilated Cardiomyopathy in a Chinese Population.Appl Biochem Biotechnol. 2017 Jul;182(3):885-897. doi: 10.1007/s12010-016-2368-1. Epub 2016 Dec 17.
• [2] LMO7 exerts an effect on mitosis progression and the spindle assembly checkpoint.Int J Biochem Cell Biol. 2018 Jan;94:22-30. doi: 10.1016/j.biocel.2017.11.006. Epub 2017 Nov 20.
• [3] LMO7 and LIMCH1 interact with LRIG proteins in lung cancer, with prognostic implications for early-stage disease.Lung Cancer. 2018 Nov;125:174-184. doi: 10.1016/j.lungcan.2018.09.017. Epub 2018 Sep 24.
• [4] Altered chromosomal positioning, compaction, and gene expression with a lamin A/C gene mutation.PLoS One. 2010 Dec 14;5(12):e14342. doi: 10.1371/journal.pone.0014342.
• [5] LRIG1? and LMO7 immunoreactivity in vulvar squamous cell carcinoma: Association with prognosis in relation to HPVDNA and p16INK4a status.Oncol Rep. 2019 Jul;42(1):142-150. doi: 10.3892/or.2019.7138. Epub 2019 May 2.
• [6] Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma.Sci Rep. 2018 Feb 15;8(1):3124. doi: 10.1038/s41598-018-20435-9.
• [7] LMO7-null mice exhibit phenotypes consistent with emery-dreifuss muscular dystrophy.Muscle Nerve. 2015 Feb;51(2):222-8. doi: 10.1002/mus.24286. Epub 2014 Nov 19.
• [8] A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci.PLoS Genet. 2011 Sep;7(9):e1002293. doi: 10.1371/journal.pgen.1002293. Epub 2011 Sep 29.
• [9] LMO7 Is a Negative Feedback Regulator of Transforming Growth Factor Signaling and Fibrosis.Circulation. 2019 Jan 29;139(5):679-693. doi: 10.1161/CIRCULATIONAHA.118.034615.
• [10] Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.Transl Psychiatry. 2017 Oct 24;7(10):e1249. doi: 10.1038/tp.2017.210.
• [11] Identification of a Recurrent LMO7-BRAF Fusion in Papillary Thyroid Carcinoma.Thyroid. 2018 Jun;28(6):748-754. doi: 10.1089/thy.2017.0258. Epub 2018 May 16.
• [12] Genome-wide association study in a Chinese population with diabetic retinopathy.Hum Mol Genet. 2013 Aug 1;22(15):3165-73. doi: 10.1093/hmg/ddt161. Epub 2013 Apr 4.
• [13] 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.
• [14] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [15] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [16] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [19] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [20] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [21] 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.
• [22] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [23] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [24] Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray. Acta Pharmacol Sin. 2004 Oct;25(10):1327-33.
• [25] 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.
• [26] 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.
• [27] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [28] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [29] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [30] 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.
• [31] 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.
• [32] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [33] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.