Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT60W9CN)

• DOT Name: Dexamethasone-induced protein (DEXI)
• Synonyms: Protein MYLE
• Gene Name: DEXI
• Related Disease:
  Acute myelogenous leukaemia
  B-cell neoplasm
  Classic Hodgkin lymphoma
  Type-1/2 diabetes
  Asthma
  Autoimmune disease
  Multiple sclerosis
  Seasonal allergic rhinitis
  Pulmonary emphysema
• UniProt ID: DEXI_HUMAN
• Pfam ID: PF15198
• Sequence:
  MLGARVAAHLDALGPLVPYVPPPLLPSMFYVGLFFVNVLILYYAFLMEYIVLNVGLVFLP
  EDMDQALVDLGVLSDPGSGLYDADSELDVFDAYLE
• Tissue Specificity: Highest levels in heart. Also expressed in brain, liver, pancreas, placenta and lung. Up-regulated in emphysematous lung compared to normal lung.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Classic Hodgkin lymphoma	DISV1LU6	Definitive	Biomarker	[1]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[2]
Asthma	DISW9QNS	Strong	Genetic Variation	[3]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[4]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[5]
Seasonal allergic rhinitis	DIS58KQX	Strong	Genetic Variation	[3]
Pulmonary emphysema	DIS5M7HZ	moderate	Altered Expression	[6]

3 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 Dexamethasone-induced protein (DEXI).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Dexamethasone-induced protein (DEXI).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Dexamethasone-induced protein (DEXI).	[10]

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 Dexamethasone-induced protein (DEXI).	[9]

References

• [1] New fusion transcripts identified in normal karyotype acute myeloid leukemia.PLoS One. 2012;7(12):e51203. doi: 10.1371/journal.pone.0051203. Epub 2012 Dec 12.
• [2] Clarifying the function of genes at the chromosome 16p13 locus in type 1 diabetes: CLEC16A and DEXI.Genes Immun. 2020 Feb;21(2):79-82. doi: 10.1038/s41435-019-0087-7. Epub 2019 Oct 1.
• [3] Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.J Allergy Clin Immunol. 2014 Jun;133(6):1564-71. doi: 10.1016/j.jaci.2013.10.030. Epub 2013 Dec 31.
• [4] Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci.Nat Commun. 2015 Nov 30;6:10069. doi: 10.1038/ncomms10069.
• [5] Multiple sclerosis-associated single-nucleotide polymorphisms in CLEC16A correlate with reduced SOCS1 and DEXI expression in the thymus.Genes Immun. 2013 Jan;14(1):62-6. doi: 10.1038/gene.2012.52. Epub 2012 Nov 15.
• [6] Cloning of dexamethasone-induced transcript: a novel glucocorticoid-induced gene that is upregulated in emphysema.Am J Respir Cell Mol Biol. 2001 Jul;25(1):119-24. doi: 10.1165/ajrcmb.25.1.4417.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.