Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW6CO2I)

• DOT Name: Fanconi anemia core complex-associated protein 24 (FAAP24)
• Synonyms: Fanconi anemia-associated protein of 24 kDa
• Gene Name: FAAP24
• Related Disease:
  Fanconi anemia complementation group A
  Fanconi's anemia
  Lymphoproliferative syndrome
• UniProt ID: FAP24_HUMAN
• PDB ID: 2LYH; 2M9M; 2M9N; 4BXO; 4M6W
• Pfam ID: PF12826 ; PF17949
• Sequence:
  MEKNPPDDTGPVHVPLGHIVANEKWRGSQLAQEMQGKIKLIFEDGLTPDFYLSNRCCILY
  VTEADLVAGNGYRKRLVRVRNSNNLKGIVVVEKTRMSEQYFPALQKFTVLDLGMVLLPVA
  SQMEASCLVIQLVQEQTKEPSKNPLLGKKRALLLSEPSLLRTVQQIPGVGKVKAPLLLQK
  FPSIQQLSNASIGELEQVVGQAVAQQIHAFFTQPR
• Function: Plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. Regulates FANCD2 monoubiquitination upon DNA damage. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed. Targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA.
• KEGG Pathway: Fanconi anemia pathway (hsa03460)
• Reactome Pathway:
  PKR-mediated signaling (R-HSA-9833482)
  Fanconi Anemia Pathway (R-HSA-6783310)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[1]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[1]
Lymphoproliferative syndrome	DISMVL8O	Strong	Genetic Variation	[1]

7 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 Fanconi anemia core complex-associated protein 24 (FAAP24).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fanconi anemia core complex-associated protein 24 (FAAP24).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Fanconi anemia core complex-associated protein 24 (FAAP24).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fanconi anemia core complex-associated protein 24 (FAAP24).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Fanconi anemia core complex-associated protein 24 (FAAP24).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fanconi anemia core complex-associated protein 24 (FAAP24).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Fanconi anemia core complex-associated protein 24 (FAAP24).	[8]

References

• [1] Fatal Lymphoproliferative Disease in Two Siblings Lacking Functional FAAP24.J Clin Immunol. 2016 Oct;36(7):684-92. doi: 10.1007/s10875-016-0317-y. Epub 2016 Jul 29.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] 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.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.