Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ7VJTX)

• DOT Name: Leptin receptor overlapping transcript-like 1 (LEPROTL1)
• Synonyms: Endospanin-2
• Gene Name: LEPROTL1
• Related Disease: Migraine disorder
• UniProt ID: LERL1_HUMAN
• Pfam ID: PF04133
• Sequence:
  MAGIKALISLSFGGAIGLMFLMLGCALPIYNKYWPLFVLFFYILSPIPYCIARRLVDDTD
  AMSNACKELAIFLTTGIVVSAFGLPIVFARAHLIEWGACALVLTGNTVIFATILGFFLVF
  GSNDDFSWQQW
• Function: 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: Widely expressed, with highest expression in heart, testis, adrenal gland, thymus, and spleen, and lowest expression in lung and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Migraine disorder	DISFCQTG	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Leptin receptor overlapping transcript-like 1 (LEPROTL1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leptin receptor overlapping transcript-like 1 (LEPROTL1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Leptin receptor overlapping transcript-like 1 (LEPROTL1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Leptin receptor overlapping transcript-like 1 (LEPROTL1).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Leptin receptor overlapping transcript-like 1 (LEPROTL1).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Leptin receptor overlapping transcript-like 1 (LEPROTL1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Leptin receptor overlapping transcript-like 1 (LEPROTL1).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Leptin receptor overlapping transcript-like 1 (LEPROTL1).	[9]

References

• [1] Genome-wide meta-analysis identifies new susceptibility loci for migraine.Nat Genet. 2013 Aug;45(8):912-917. doi: 10.1038/ng.2676. Epub 2013 Jun 23.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] 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.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.