Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJMU7N6)

• DOT Name: Uncharacterized protein C4orf19 (C4ORF19)
• Gene Name: C4ORF19
• Related Disease:
  Acute myelogenous leukaemia
  Cholestasis
• UniProt ID: CD019_HUMAN
• Pfam ID: PF15770
• Sequence:
  MGCRCCKIIQSYLFDPVQVPSPGYVNEVNSCKLDEDDTDKLKGKWSSEVLVQKNDPQRQG
  SKKTESSSRTADPWEPCWPHQGPLPQGDAGGEHHACGVNGIGPAATPQPTGNSSPTQDDR
  GSWASTANTVPPTQPFLEGGGTRKQDCVLLASEGTQVMRNGDSRAPSEAESFALEVQDHV
  FQIPAPDYLQHWGPAGDNVDHNEKDCVFKNHTEDESLEGIQPPVGEHGLNTPFSVRRSWD
  SLNEDVETEVLSICFNEKGPVHAMPVVDSGNRQEDTHGSDGDGDGEIVDEDAAVAEALAA
  LEAATAGEDLDETD

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[1]
Cholestasis	DISDJJWE	Limited	Biomarker	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Uncharacterized protein C4orf19 (C4ORF19) affects the response to substance of Etoposide.	[15]

10 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 Uncharacterized protein C4orf19 (C4ORF19).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Uncharacterized protein C4orf19 (C4ORF19).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Uncharacterized protein C4orf19 (C4ORF19).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Uncharacterized protein C4orf19 (C4ORF19).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Uncharacterized protein C4orf19 (C4ORF19).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Uncharacterized protein C4orf19 (C4ORF19).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Uncharacterized protein C4orf19 (C4ORF19).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Uncharacterized protein C4orf19 (C4ORF19).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Uncharacterized protein C4orf19 (C4ORF19).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Uncharacterized protein C4orf19 (C4ORF19).	[14]

2 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 Uncharacterized protein C4orf19 (C4ORF19).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Uncharacterized protein C4orf19 (C4ORF19).	[13]

References

• [1] 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.
• [2] 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.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] 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.
• [10] 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.
• [11] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [12] 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.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] 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.
• [15] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.