Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2EENVA)

DOT Name Leptin receptor gene-related protein (LEPROT)
Synonyms Endospanin-1; Leptin receptor overlapping transcript protein; OB-R gene-related protein; OB-RGRP
Gene Name LEPROT
Related Disease
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Epilepsy ( )
Intellectual disability ( )
Periodontitis ( )
UniProt ID
OBRG_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF04133
Sequence
MAGVKALVALSFSGAIGLTFLMLGCALEDYGVYWPLFVLIFHAISPIPHFIAKRVTYDSD
ATSSACRELAYFFTTGIVVSAFGFPVILARVAVIKWGACGLVLAGNAVIFLTIQGFFLIF
GRGDDFSWEQW
Function
Negatively regulates leptin receptor (LEPR) cell surface expression, and thus decreases response to leptin. Negatively regulates growth hormone (GH) receptor cell surface expression in liver. May play a role in liver resistance to GH during periods of reduced nutrient availability.
Tissue Specificity Expressed at the highest levels in heart and placenta and at a lesser extent in lung, liver, skeletal muscle, kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Altered Expression [1]
Breast cancer DIS7DPX1 Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Biomarker [2]
Epilepsy DISBB28L Strong Biomarker [3]
Intellectual disability DISMBNXP Strong Biomarker [3]
Periodontitis DISI9JOI Limited Altered Expression [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Leptin receptor gene-related protein (LEPROT). [5]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Leptin receptor gene-related protein (LEPROT). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Leptin receptor gene-related protein (LEPROT). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Leptin receptor gene-related protein (LEPROT). [8]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Leptin receptor gene-related protein (LEPROT). [9]
Testosterone DM7HUNW Approved Testosterone increases the expression of Leptin receptor gene-related protein (LEPROT). [9]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Leptin receptor gene-related protein (LEPROT). [10]
Menadione DMSJDTY Approved Menadione affects the expression of Leptin receptor gene-related protein (LEPROT). [11]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Leptin receptor gene-related protein (LEPROT). [12]
Bilirubin DMI0V4O Investigative Bilirubin decreases the expression of Leptin receptor gene-related protein (LEPROT). [13]
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References

1 Superactive human leptin antagonist (SHLA), triple Lan1 and quadruple Lan2 leptin mutein as a promising treatment for human folliculoma.Cancer Chemother Pharmacol. 2017 Oct;80(4):815-827. doi: 10.1007/s00280-017-3423-5. Epub 2017 Aug 31.
2 Effects of two types of energy restriction on methylation levels of adiponectin receptor 1 and leptin receptor overlapping transcript in a mouse mammary tumour virus-transforming growth factor- breast cancer mouse model.Br J Nutr. 2021 Jan 14;125(1):1-9. doi: 10.1017/S0007114519002757. Epub 2019 Nov 5.
3 Homozygous deletion of an 80 kb region comprising part of DNAJC6 and LEPR genes on chromosome 1P31.3 is associated with early onset obesity, mental retardation and epilepsy.Mol Genet Metab. 2012 Jul;106(3):345-50. doi: 10.1016/j.ymgme.2012.04.026. Epub 2012 May 10.
4 Upregulated Leptin in Periodontitis Promotes Inflammatory Cytokine Expression in Periodontal Ligament Cells.J Periodontol. 2015 Jul;86(7):917-26. doi: 10.1902/jop.2015.150030. Epub 2015 Apr 16.
5 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 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.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
10 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
11 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.
12 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
13 Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.