Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYAKC55)

• DOT Name: Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3)
• Synonyms: LDLR class A domain-containing protein 3
• Gene Name: LDLRAD3
• Related Disease:
  Drug dependence
  Substance abuse
  Substance dependence
  Acute myelogenous leukaemia
  Pancreatic cancer
• UniProt ID: LRAD3_HUMAN
• PDB ID: 7FFF; 7FFL; 7FFN
• Pfam ID: PF00057
• Sequence:
  MWLLGPLCLLLSSAAESQLLPGNNFTNECNIPGNFMCSNGRCIPGAWQCDGLPDCFDKSD
  EKECPKAKSKCGPTFFPCASGIHCIIGRFRCNGFEDCPDGSDEENCTANPLLCSTARYHC
  KNGLCIDKSFICDGQNNCQDNSDEESCESSQEPGSGQVFVTSENQLVYYPSITYAIIGSS
  VIFVLVVALLALVLHHQRKRNNLMTLPVHRLQHPVLLSRLVVLDHPHHCNVTYNVNNGIQ
  YVASQAEQNASEVGSPPSYSEALLDQRPAWYDLPPPPYSSDTESLNQADLPPYRSRSGSA
  NSASSQAASSLLSVEDTSHSPGQPGPQEGTAEPRDSEPSQGTEEV
• Function: May influence APP processing, resulting in a decrease in sAPP-alpha production and increased amyloidogenic P3 peptide production. May regulate ITCH and NEDD4 E3 ligase activity and degradation ; (Microbial infection) Acts as a receptor for Venezuelan equine encephalitis virus.
• Tissue Specificity: Expressed at high levels in brain, lung, skeletal muscle, and pancreas. Expressed at moderate levels in heart, placenta, and kidney but not detected in the liver.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Drug dependence	DIS9IXRC	Strong	Biomarker	[1]
Substance abuse	DIS327VW	Strong	Biomarker	[1]
Substance dependence	DISDRAAR	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]
Pancreatic cancer	DISJC981	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3).	[8]
Nicotine	DMWX5CO	Approved	Nicotine increases the splicing of Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3).	[9]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3).	[14]

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 increases the methylation of Low-density lipoprotein receptor class A domain-containing protein 3 (LDLRAD3).	[12]

References

• [1] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Downregulation of circular RNA circ-LDLRAD3 suppresses pancreatic cancer progression through miR-137-3p/PTN axis.Life Sci. 2019 Dec 15;239:116871. doi: 10.1016/j.lfs.2019.116871. Epub 2019 Sep 12.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [10] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [11] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [12] 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.
• [13] 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.
• [14] 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.