Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKRPBW1)

• DOT Name: Fanconi anemia group E protein (FANCE)
• Synonyms: Protein FACE
• Gene Name: FANCE
• Related Disease:
  Breast cancer
  Breast carcinoma
  Fanconi anemia complementation group E
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Advanced cancer
  Colorectal carcinoma
  Fanconi anemia complementation group A
  Head-neck squamous cell carcinoma
  Leukemia
  Myelodysplastic syndrome
  Pancytopenia
  Psoriasis
  Fanconi's anemia
• UniProt ID: FANCE_HUMAN
• PDB ID: 2ILR; 7KZP; 7KZQ; 7KZR; 7KZS; 7KZT; 7KZV
• Pfam ID: PF11510
• Sequence:
  MATPDAGLPGAEGVEPAPWAQLEAPARLLLQALQAGPEGARRGLGVLRALGSRGWEPFDW
  GRLLEALCREEPVVQGPDGRLELKPLLLRLPRICQRNLMSLLMAVRPSLPESGLLSVLQI
  AQQDLAPDPDAWLRALGELLRRDLGVGTSMEGASPLSERCQRQLQSLCRGLGLGGRRLKS
  PQAPDPEEEENRDSQQPGKRRKDSEEEAASPEGKRVPKRLRCWEEEEDHEKERPEHKSLE
  SLADGGSASPIKDQPVMAVKTGEDGSNLDDAKGLAESLELPKAIQDQLPRLQQLLKTLEE
  GLEGLEDAPPVELQLLHECSPSQMDLLCAQLQLPQLSDLGLLRLCTWLLALSPDLSLSNA
  TVLTRSLFLGRILSLTSSASRLLTTALTSFCAKYTYPVCSALLDPVLQAPGTGPAQTELL
  CCLVKMESLEPDAQVLMLGQILELPWKEETFLVLQSLLERQVEMTPEKFSVLMEKLCKKG
  LAATTSMAYAKLMLTVMTKYQANITETQRLGLAMALEPNTTFLRKSLKAALKHLGP
• Function: As part of the Fanconi anemia (FA) complex functions in DNA cross-links repair. Required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2.
• 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

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[1]
Fanconi anemia complementation group E	DIS65STL	Definitive	Autosomal recessive	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[5]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[6]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[6]
Leukemia	DISNAKFL	Strong	Biomarker	[3]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[3]
Pancytopenia	DISVKEHV	Strong	Biomarker	[3]
Psoriasis	DIS59VMN	Strong	Biomarker	[7]
Fanconi's anemia	DISGW6Q8	Supportive	Autosomal recessive	[8]

12 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 Fanconi anemia group E protein (FANCE).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Fanconi anemia group E protein (FANCE).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Fanconi anemia group E protein (FANCE).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fanconi anemia group E protein (FANCE).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Fanconi anemia group E protein (FANCE).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Fanconi anemia group E protein (FANCE).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Fanconi anemia group E protein (FANCE).	[15]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Fanconi anemia group E protein (FANCE).	[15]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Fanconi anemia group E protein (FANCE).	[16]
LY2835219	DM93VBZ	Approved	LY2835219 decreases the expression of Fanconi anemia group E protein (FANCE).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Fanconi anemia group E protein (FANCE).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fanconi anemia group E protein (FANCE).	[20]

3 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 increases the methylation of Fanconi anemia group E protein (FANCE).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Fanconi anemia group E protein (FANCE).	[19]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Fanconi anemia group E protein (FANCE).	[19]

References

• [1] Analysis of a FANCE Splice Isoform in Regard to DNA Repair.J Mol Biol. 2015 Sep 25;427(19):3056-73. doi: 10.1016/j.jmb.2015.08.004. Epub 2015 Aug 12.
• [2] 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.
• [3] Germline Genetic Predisposition to Hematologic Malignancy.J Clin Oncol. 2017 Mar 20;35(9):1018-1028. doi: 10.1200/JCO.2016.70.8644. Epub 2017 Feb 13.
• [4] Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.J Cancer Res Clin Oncol. 2018 Dec;144(12):2495-2513. doi: 10.1007/s00432-018-2763-9. Epub 2018 Oct 10.
• [5] The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer.Eur J Hum Genet. 2016 Oct;24(10):1501-5. doi: 10.1038/ejhg.2016.44. Epub 2016 May 11.
• [6] Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50.Cancer. 2017 Oct 15;123(20):3943-3954. doi: 10.1002/cncr.30802. Epub 2017 Jul 5.
• [7] Dimethyl fumarate (DMF) vs. monoethyl fumarate (MEF) salts for the treatment of plaque psoriasis: a review of clinical data.Arch Dermatol Res. 2018 Aug;310(6):475-483. doi: 10.1007/s00403-018-1825-9. Epub 2018 Mar 24.
• [8] 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.
• [9] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [10] 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.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [14] 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.
• [15] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [16] Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature. Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.