Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFE7WZW)

• DOT Name: Tripartite motif-containing protein 46 (TRIM46)
• Synonyms: Gene Y protein; GeneY; Tripartite, fibronectin type-III and C-terminal SPRY motif protein
• Gene Name: TRIM46
• Related Disease:
  Breast cancer
  Breast carcinoma
  Dental caries
  Gastric cancer
  Gout
  Non-small-cell lung cancer
  Stomach cancer
  Acute myelogenous leukaemia
  Small-cell lung cancer
• UniProt ID: TRI46_HUMAN
• Pfam ID: PF18568 ; PF00643 ; PF13445
• Sequence:
  MAEGEDMQTFTSIMDALVRISTSMKNMEKELLCPVCQEMYKQPLVLPCTHNVCQACAREV
  LGQQGYIGHGGDPSSEPTSPASTPSTRSPRLSRRTLPKPDRLDRLLKSGFGTYPGRKRGA
  LHPQVIMFPCPACQGDVELGERGLAGLFRNLTLERVVERYRQSVSVGGAILCQLCKPPPL
  EATKGCTECRATFCNECFKLFHPWGTQKAQHEPTLPTLSFRPKGLMCPDHKEEVTHYCKT
  CQRLVCQLCRVRRTHSGHKITPVLSAYQALKDKLTKSLTYILGNQDTVQTQICELEEAVR
  HTEVSGQQAKEEVSQLVRGLGAVLEEKRASLLQAIEECQQERLARLSAQIQEHRSLLDGS
  GLVGYAQEVLKETDQPCFVQAAKQLHNRIARATEALQTFRPAASSSFRHCQLDVGREMKL
  LTELNFLRVPEAPVIDTQRTFAYDQIFLCWRLPPHSPPAWHYTVEFRRTDVPAQPGPTRW
  QRREEVRGTSALLENPDTGSVYVLRVRGCNKAGYGEYSEDVHLHTPPAPVLHFFLDSRWG
  ASRERLAISKDQRAVRSVPGLPLLLAADRLLTGCHLSVDVVLGDVAVTQGRSYWACAVDP
  ASYLVKVGVGLESKLQESFQGAPDVISPRYDPDSGHDSGAEDATVEASPPFAFLTIGMGK
  ILLGSGASSNAGLTGRDGPTAGCTVPLPPRLGICLDYERGRVSFLDAVSFRGLLECPLDC
  SGPVCPAFCFIGGGAVQLQEPVGTKPERKVTIGGFAKLD
• Function: Microtubule-associated protein that is involved in the formation of parallel microtubule bundles linked by cross-bridges in the proximal axon. Required for the uniform orientation and maintenance of the parallel microtubule fascicles, which are important for efficient cargo delivery and trafficking in axons. Thereby also required for proper axon specification, the establishment of neuronal polarity and proper neuronal migration.
• Reactome Pathway: Interferon gamma signaling (R-HSA-877300)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Dental caries	DISRBCMD	Strong	Genetic Variation	[3]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[4]
Gout	DISHC0U7	Strong	Genetic Variation	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[4]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[7]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[8]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Uric acid	DMA1MKT	Investigative	Tripartite motif-containing protein 46 (TRIM46) affects the abundance of Uric acid.	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tripartite motif-containing protein 46 (TRIM46).	[9]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Tripartite motif-containing protein 46 (TRIM46).	[10]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Tripartite motif-containing protein 46 (TRIM46).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tripartite motif-containing protein 46 (TRIM46).	[13]

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 affects the methylation of Tripartite motif-containing protein 46 (TRIM46).	[12]

References

• [1] Mmu-miR-1894-3p Inhibits Cell Proliferation and Migration of Breast Cancer Cells by Targeting Trim46.Int J Mol Sci. 2016 Apr 22;17(4):609. doi: 10.3390/ijms17040609.
• [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] Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.Nat Commun. 2019 Jun 24;10(1):2773. doi: 10.1038/s41467-019-10630-1.
• [4] Association of high-evidence gastric cancer susceptibility loci and somatic gene expression levels with survival.Carcinogenesis. 2017 Oct 26;38(11):1119-1128. doi: 10.1093/carcin/bgx090.
• [5] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
• [6] TRIM59 Promotes the Proliferation and Migration of Non-Small Cell Lung Cancer Cells by Upregulating Cell Cycle Related Proteins.PLoS One. 2015 Nov 24;10(11):e0142596. doi: 10.1371/journal.pone.0142596. eCollection 2015.
• [7] 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.
• [8] Antibodies to TRIM46 are associated with paraneoplastic neurological syndromes.Ann Clin Transl Neurol. 2017 Jul 28;4(9):680-686. doi: 10.1002/acn3.396. eCollection 2017 Sep.
• [9] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [10] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [11] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [14] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.