Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9VDGPR)

• DOT Name: Leucine-rich repeat-containing protein 3B (LRRC3B)
• Synonyms: Leucine-rich repeat protein 15
• Gene Name: LRRC3B
• Related Disease:
  Coronary atherosclerosis
  Coronary heart disease
  Gastric cancer
  Myocardial infarction
  Stroke
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Clear cell renal carcinoma
  Colorectal carcinoma
  Hereditary diffuse gastric adenocarcinoma
  Leukemia
  Neoplasm
  Renal cell carcinoma
  Gastric neoplasm
  Ovarian cancer
  Prostate cancer
  Prostate carcinoma
  Colorectal neoplasm
  Acute myelogenous leukaemia
• UniProt ID: LRC3B_HUMAN
• PDB ID: 5EMA
• Pfam ID: PF00560 ; PF13855 ; PF01462
• Sequence:
  MNLVDLWLTRSLSMCLLLQSFVLMILCFHSASMCPKGCLCSSSGGLNVTCSNANLKEIPR
  DLPPETVLLYLDSNQITSIPNEIFKDLHQLRVLNLSKNGIEFIDEHAFKGVAETLQTLDL
  SDNRIQSVHKNAFNNLKARARIANNPWHCDCTLQQVLRSMASNHETAHNVICKTSVLDEH
  AGRPFLNAANDADLCNLPKKTTDYAMLVTMFGWFTMVISYVVYYVRQNQEDARRHLEYLK
  SLPSRQKKADEPDDISTVV

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coronary atherosclerosis	DISKNDYU	Definitive	Biomarker	[1]
Coronary heart disease	DIS5OIP1	Definitive	Biomarker	[1]
Gastric cancer	DISXGOUK	Definitive	Biomarker	[2]
Myocardial infarction	DIS655KI	Definitive	Genetic Variation	[1]
Stroke	DISX6UHX	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Posttranslational Modification	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[6]
Leukemia	DISNAKFL	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Renal cell carcinoma	DISQZ2X8	Strong	Posttranslational Modification	[2]
Gastric neoplasm	DISOKN4Y	moderate	Biomarker	[6]
Ovarian cancer	DISZJHAP	moderate	Altered Expression	[8]
Prostate cancer	DISF190Y	moderate	Genetic Variation	[8]
Prostate carcinoma	DISMJPLE	moderate	Genetic Variation	[8]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[5]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[9]

7 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 Leucine-rich repeat-containing protein 3B (LRRC3B).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich repeat-containing protein 3B (LRRC3B).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Leucine-rich repeat-containing protein 3B (LRRC3B).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Leucine-rich repeat-containing protein 3B (LRRC3B).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Leucine-rich repeat-containing protein 3B (LRRC3B).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Leucine-rich repeat-containing protein 3B (LRRC3B).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Leucine-rich repeat-containing protein 3B (LRRC3B).	[17]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Leucine-rich repeat-containing protein 3B (LRRC3B).	[11]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Leucine-rich repeat-containing protein 3B (LRRC3B).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Leucine-rich repeat-containing protein 3B (LRRC3B).	[16]

References

• [1] Admixture Mapping of Subclinical Atherosclerosis and Subsequent Clinical Events Among African Americans in 2 Large Cohort Studies.Circ Cardiovasc Genet. 2017 Apr;10(2):e001569. doi: 10.1161/CIRCGENETICS.116.001569.
• [2] Methylation pattern of the putative tumor-suppressor gene LRRC3B promoter in clear cell renal cell carcinomas.Mol Med Rep. 2012 Feb;5(2):509-12. doi: 10.3892/mmr.2011.681. Epub 2011 Nov 16.
• [3] Protective role of LRRC3B in preventing breast cancer metastasis and recurrence post-bupivacaine.Oncol Lett. 2017 Oct;14(4):5013-5017. doi: 10.3892/ol.2017.6773. Epub 2017 Aug 18.
• [4] A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer.Nat Genet. 2018 Jul;50(7):968-978. doi: 10.1038/s41588-018-0132-x. Epub 2018 Jun 18.
• [5] Epigenetic silencing of LRRC3B in colorectal cancer.Scand J Gastroenterol. 2009;44(1):79-84. doi: 10.1080/00365520802400834.
• [6] LRRC3B, encoding a leucine-rich repeat-containing protein, is a putative tumor suppressor gene in gastric cancer.Cancer Res. 2008 Sep 1;68(17):7147-55. doi: 10.1158/0008-5472.CAN-08-0667.
• [7] The clinical value of LRRC3B gene expression and promoter hypermethylation in breast carcinomas.Cell Biochem Biophys. 2014 Nov;70(2):1035-41. doi: 10.1007/s12013-014-0018-1.
• [8] LRRC3B gene is frequently epigenetically inactivated in several epithelial malignancies and inhibits cell growth and replication.Biochimie. 2012 May;94(5):1151-7. doi: 10.1016/j.biochi.2012.01.019. Epub 2012 Feb 2.
• [9] 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.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [12] 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.
• [13] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [14] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [15] 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.
• [16] 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.
• [17] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.