Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT65IL83)

• DOT Name: Protein LRATD1 (LRATD1)
• Synonyms: LRAT domain-containing 1; Neurologic sensory protein 1; NSE1; Protein FAM84A
• Gene Name: LRATD1
• Related Disease:
  Adenoma
  Advanced cancer
  Carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Liver cancer
  Neoplasm
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate carcinoma
  Feingold syndrome
• UniProt ID: LRAT1_HUMAN
• Pfam ID: PF04970
• Sequence:
  MGNQLDRITHLNYSELPTGDPSGIEKDELRVGVAYFFSDDEEDLDERGQPDKFGVKAPPG
  CTPCPESPSRHHHHLLHQLVLNETQFSAFRGQECIFSKVSGGPQGADLSVYAVTALPALC
  EPGDLLELLWLQPAPEPPAPAPHWAVYVGGGQIIHLHQGEIRQDSLYEAGAANVGRVVNS
  WYRYRPLVAELVVQNACGHLGLKSEEICWTNSESFAAWCRFGKREFKAGGEVPAGTQPPQ
  QQYYLKVHLGENKVHTARFHSLEDLIREKRRIDASGRLRVLQELADLVDDKE
• Function: May play a role in cell morphology and motility.
• Tissue Specificity: Only detected in testis. Highly expressed in colon cancer cells.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[3]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[3]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[3]
Liver cancer	DISDE4BI	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]
Feingold syndrome	DIS18KX1	Limited	Genetic Variation	[5]

9 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 Protein LRATD1 (LRATD1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein LRATD1 (LRATD1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein LRATD1 (LRATD1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein LRATD1 (LRATD1).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Protein LRATD1 (LRATD1).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Protein LRATD1 (LRATD1).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein LRATD1 (LRATD1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein LRATD1 (LRATD1).	[13]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Protein LRATD1 (LRATD1).	[14]

References

• [1] Nuclear receptor CAR-regulated expression of the FAM84A gene during the development of mouse liver tumors.Int J Oncol. 2011 Jun;38(6):1511-20. doi: 10.3892/ijo.2011.980. Epub 2011 Mar 17.
• [2] Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling.PLoS One. 2008 Apr 30;3(4):e2079. doi: 10.1371/journal.pone.0002079.
• [3] A gene encoding a family with sequence similarity 84, member A (FAM84A) enhanced migration of human colon cancer cells.Int J Oncol. 2006 Aug;29(2):341-7.
• [4] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [5] A de novo 4.4-Mb microdeletion in 2p24.3 ?p24.2 in a girl with bilateral hearing impairment, microcephaly, digit abnormalities and Feingold syndrome.Eur J Med Genet. 2012 Nov;55(11):666-9. doi: 10.1016/j.ejmg.2012.07.003. Epub 2012 Jul 25.
• [6] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [7] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [12] 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.
• [13] 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.
• [14] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.