Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3WA9N1)

• DOT Name: Fanconi anemia group F protein (FANCF)
• Synonyms: Protein FACF
• Gene Name: FANCF
• Related Disease:
  Fanconi anemia complementation group F
  Fanconi's anemia
• UniProt ID: FANCF_HUMAN
• PDB ID: 2IQC; 7KZP; 7KZQ; 7KZR; 7KZS; 7KZT; 7KZV
• Pfam ID: PF11107
• Sequence:
  MESLLQHLDRFSELLAVSSTTYVSTWDPATVRRALQWARYLRHIHRRFGRHGPIRTALER
  RLHNQWRQEGGFGRGPVPGLANFQALGHCDVLLSLRLLENRALGDAARYHLVQQLFPGPG
  VRDADEETLQESLARLARRRSAVHMLRFNGYRENPNLQEDSLMKTQAELLLERLQEVGKA
  EAERPARFLSSLWERLPQNNFLKVIAVALLQPPLSRRPQEELEPGIHKSPGEGSQVLVHW
  LLGNSEVFAAFCRALPAGLLTLVTSRHPALSPVYLGLLTDWGQRLHYDLQKGIWVGTESQ
  DVPWEELHNRFQSLCQAPPPLKDKVLTALETCKAQDGDFEVPGLSIWTDLLLALRSGAFR
  KRQVLGLSAGLSSV
• Function: DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fanconi anemia complementation group F	DISL2QE9	Definitive	Autosomal recessive	[1]
Fanconi's anemia	DISGW6Q8	Supportive	Autosomal recessive	[2]

9 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 group F protein (FANCF).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fanconi anemia group F protein (FANCF).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fanconi anemia group F protein (FANCF).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Fanconi anemia group F protein (FANCF).	[7]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Fanconi anemia group F protein (FANCF).	[6]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Fanconi anemia group F protein (FANCF).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Fanconi anemia group F protein (FANCF).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Fanconi anemia group F protein (FANCF).	[11]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Fanconi anemia group F protein (FANCF).	[12]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Fanconi anemia group F protein (FANCF).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fanconi anemia group F protein (FANCF).	[10]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Fanconi Anemia. 2002 Feb 14 [updated 2021 Jun 3]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Ouabain, a cardiac glycoside, inhibits the Fanconi anemia/BRCA pathway activated by DNA interstrand cross-linking agents. PLoS One. 2013 Oct 4;8(10):e75905. doi: 10.1371/journal.pone.0075905. eCollection 2013.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [12] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.