Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4961W1)

• DOT Name: SET domain-containing protein 9 (SETD9)
• Synonyms: EC 2.1.1.-
• Gene Name: SETD9
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: SETD9_HUMAN
• EC Number: 2.1.1.-
• Sequence:
  MPGRLLRGLWQRWRRYKYRFVPWIALNLSHNPRTLRYVPEESKDKVISDEDVLGTLLKVF
  QALFLNDFNKQSEILSMLPESVKSKYQDLLAVEHQGVKLLENRHQQQSTFKPEEILYKTL
  GFSVAQATSSLISAGKGVFVTKGLVPKGAVVSMYPGTVYQKYEPIFFQSIGNPFIFRCLD
  GVLIDGNDKGISKVVYRSCNGRDRLGPLKMSDSTWLTSEIHNPLAVGQYVNNCSNDRAAN
  VCYQEFDVPAVFPIELKQYLPNIAYSYDKQSPLRCVVLVALRDINQGEELFSNYYTIVS
• Reactome Pathway: Regulation of TP53 Activity through Methylation (R-HSA-6804760)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of SET domain-containing protein 9 (SETD9).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SET domain-containing protein 9 (SETD9).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SET domain-containing protein 9 (SETD9).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SET domain-containing protein 9 (SETD9).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of SET domain-containing protein 9 (SETD9).	[6]

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 decreases the methylation of SET domain-containing protein 9 (SETD9).	[7]

References

• [1] SNP variants at the MAP3K1/SETD9 locus 5q11.2 associate with somatic PIK3CA variants in breast cancers.Eur J Hum Genet. 2017 Feb;25(3):384-387. doi: 10.1038/ejhg.2016.179. Epub 2016 Dec 28.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] 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.