Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTERQO47)

• DOT Name: Protein LEKR1 (LEKR1)
• Gene Name: LEKR1
• Related Disease:
  Diabetic retinopathy
  Non-insulin dependent diabetes
  Breast carcinoma
• UniProt ID: LEKR1_HUMAN
• Sequence:
  MDHHIPMHALPEEIQKMLPEEKVCKYCGVSYLILHEFKAMEEKVKAMEKEMKFYQGSVDR
  EKRLQEKLHSLSQELEQYKIDNKSKTERIYDVGMQLKSQQNEFQKVKKQLSHLQDELKIK
  YRQSYIFRLCFC

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic retinopathy	DISHGUJM	Definitive	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]

3 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 Protein LEKR1 (LEKR1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein LEKR1 (LEKR1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Protein LEKR1 (LEKR1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein LEKR1 (LEKR1).	[4]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Protein LEKR1 (LEKR1).	[5]

References

• [1] Association between LEKR1-CCNL1 and IGSF21-KLHDC7A gene polymorphisms and diabetic retinopathy of type 2 diabetes mellitus in the Chinese Han population.J Gene Med. 2016 Oct;18(10):282-287. doi: 10.1002/jgm.2926.
• [2] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [3] 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.
• [4] 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.
• [5] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [6] 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.
• [7] 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.