Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ2OSMR)

• DOT Name: KRAB domain-containing protein 4 (KRBOX4)
• Synonyms: KRAB box domain-containing protein 4
• Gene Name: KRBOX4
• Related Disease: Promyelocytic leukaemia
• UniProt ID: KRBX4_HUMAN
• Pfam ID: PF01352
• Sequence:
  MAMSQESLTFKDVFVDFTLEEWQQLDSAQKNLYRDVMLENYSHLVSVGYLVAKPDVIFRL
  GPGEESWMADGGTPVRTCAGEDRPEVWQVDEQIDHYKESQDKLPWQAAFIGKETLKDESG
  QESRTCRKSIYLSTEFDSVRQRLPKYYSWEKAFKTSFKLSWSKWKLCKKER
• Tissue Specificity: Expressed in brain, ovary, testis, prostate, tonsil, heart, bone marrow, colon, breast and kidney.
• Reactome Pathway: Generic Transcription Pathway (R-HSA-212436)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Promyelocytic leukaemia	DISYGG13	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 affects the expression of KRAB domain-containing protein 4 (KRBOX4).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of KRAB domain-containing protein 4 (KRBOX4).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of KRAB domain-containing protein 4 (KRBOX4).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of KRAB domain-containing protein 4 (KRBOX4).	[6]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of KRAB domain-containing protein 4 (KRBOX4).	[7]

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 KRAB domain-containing protein 4 (KRBOX4).	[5]

References

• [1] PML, a growth suppressor disrupted in acute promyelocytic leukemia.Mol Cell Biol. 1994 Oct;14(10):6858-67. doi: 10.1128/mcb.14.10.6858-6867.1994.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [5] 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.
• [6] 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.
• [7] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.