Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7MC8TZ)

• DOT Name: Fanconi anemia group G protein (FANCG)
• Synonyms: Protein FACG; DNA repair protein XRCC9
• Gene Name: FANCG
• Related Disease:
  Aplastic anemia
  Fanconi anemia complementation group G
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  Chromosomal disorder
  Deafness
  Epithelial ovarian cancer
  Familial pancreatic carcinoma
  Hepatocellular carcinoma
  Leukemia
  Myelodysplastic syndrome
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic tumour
  Pancytopenia
  Adenocarcinoma
  Pancreatic cancer
  Fanconi's anemia
  Non-small-cell lung cancer
  Xeroderma pigmentosum group D
  Mouth disorder
  Multiple sclerosis
• UniProt ID: FANCG_HUMAN
• PDB ID: 7KZP; 7KZQ; 7KZR; 7KZS; 7KZT; 7KZV
• Sequence:
  MSRQTTSVGSSCLDLWREKNDRLVRQAKVAQNSGLTLRRQQLAQDALEGLRGLLHSLQGL
  PAAVPVLPLELTVTCNFIILRASLAQGFTEDQAQDIQRSLERVLETQEQQGPRLEQGLRE
  LWDSVLRASCLLPELLSALHRLVGLQAALWLSADRLGDLALLLETLNGSQSGASKDLLLL
  LKTWSPPAEELDAPLTLQDAQGLKDVLLTAFAYRQGLQELITGNPDKALSSLHEAASGLC
  PRPVLVQVYTALGSCHRKMGNPQRALLYLVAALKEGSAWGPPLLEASRLYQQLGDTTAEL
  ESLELLVEALNVPCSSKAPQFLIEVELLLPPPDLASPLHCGTQSQTKHILASRCLQTGRA
  GDAAEHYLDLLALLLDSSEPRFSPPPSPPGPCMPEVFLEAAVALIQAGRAQDALTLCEEL
  LSRTSSLLPKMSRLWEDARKGTKELPYCPLWVSATHLLQGQAWVQLGAQKVAISEFSRCL
  ELLFRATPEEKEQGAAFNCEQGCKSDAALQQLRAAALISRGLEWVASGQDTKALQDFLLS
  VQMCPGNRDTYFHLLQTLKRLDRRDEATALWWRLEAQTKGSHEDALWSLPLYLESYLSWI
  RPSDRDAFLEEFRTSLPKSCDL
• 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. Candidate tumor suppressor gene.
• Tissue Specificity: Highly expressed in testis and thymus. Found in lymphoblasts.
• 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

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aplastic anemia	DISJRSC0	Definitive	Biomarker	[1]
Fanconi anemia complementation group G	DISHG6IF	Definitive	Autosomal recessive	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[5]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[4]
Deafness	DISKCLH4	Strong	Biomarker	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[7]
Familial pancreatic carcinoma	DIS1XROR	Strong	Genetic Variation	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[9]
Leukemia	DISNAKFL	Strong	Biomarker	[3]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[8]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[7]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[7]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[10]
Pancytopenia	DISVKEHV	Strong	Genetic Variation	[11]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[12]
Pancreatic cancer	DISJC981	moderate	Genetic Variation	[13]
Fanconi's anemia	DISGW6Q8	Supportive	Autosomal recessive	[14]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Genetic Variation	[15]
Xeroderma pigmentosum group D	DISFFE93	Disputed	Genetic Variation	[15]
Mouth disorder	DISX82BI	Limited	Biomarker	[16]
Multiple sclerosis	DISB2WZI	Limited	Biomarker	[17]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Melphalan	DMOLNHF	Approved	Fanconi anemia group G protein (FANCG) increases the response to substance of Melphalan.	[39]
Chlorambucil	DMRKE63	Approved	Fanconi anemia group G protein (FANCG) increases the response to substance of Chlorambucil.	[39]
Formaldehyde	DM7Q6M0	Investigative	Fanconi anemia group G protein (FANCG) increases the response to substance of Formaldehyde.	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Fanconi anemia group G protein (FANCG).	[18]

22 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fanconi anemia group G protein (FANCG).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Fanconi anemia group G protein (FANCG).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Fanconi anemia group G protein (FANCG).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fanconi anemia group G protein (FANCG).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Fanconi anemia group G protein (FANCG).	[23]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Fanconi anemia group G protein (FANCG).	[24]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Fanconi anemia group G protein (FANCG).	[25]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Fanconi anemia group G protein (FANCG).	[25]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fanconi anemia group G protein (FANCG).	[26]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Fanconi anemia group G protein (FANCG).	[27]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Fanconi anemia group G protein (FANCG).	[28]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Fanconi anemia group G protein (FANCG).	[29]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Fanconi anemia group G protein (FANCG).	[30]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Fanconi anemia group G protein (FANCG).	[31]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Fanconi anemia group G protein (FANCG).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Fanconi anemia group G protein (FANCG).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fanconi anemia group G protein (FANCG).	[33]
Arecoline	DMFJZK3	Phase 1	Arecoline decreases the expression of Fanconi anemia group G protein (FANCG).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fanconi anemia group G protein (FANCG).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fanconi anemia group G protein (FANCG).	[36]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Fanconi anemia group G protein (FANCG).	[37]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Fanconi anemia group G protein (FANCG).	[38]

References

• [1] The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC.Blood. 2002 Oct 1;100(7):2457-62. doi: 10.1182/blood-2002-03-0860.
• [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] Areca nut induces miR-23a and inhibits repair of DNA double-strand breaks by targeting FANCG.Toxicol Sci. 2011 Oct;123(2):480-90. doi: 10.1093/toxsci/kfr182. Epub 2011 Jul 12.
• [5] Lymphocytes of patients with Alzheimer's disease display different DNA damage repair kinetics and expression profiles of DNA repair and stress response genes.Int J Mol Sci. 2013 Jun 10;14(6):12380-400. doi: 10.3390/ijms140612380.
• [6] Molecular pathogenesis of Fanconi anemia: recent progress.Blood. 2006 Jun 1;107(11):4223-33. doi: 10.1182/blood-2005-10-4240. Epub 2006 Feb 21.
• [7] The identification of pathogenic variants in BRCA1/2 negative, high risk, hereditary breast and/or ovarian cancer patients: High frequency of FANCM pathogenic variants.Int J Cancer. 2019 Jun 1;144(11):2683-2694. doi: 10.1002/ijc.31992. Epub 2019 Jan 11.
• [8] The genetics of FANCC and FANCG in familial pancreatic cancer.Cancer Biol Ther. 2004 Feb;3(2):167-9. doi: 10.4161/cbt.3.2.609. Epub 2004 Feb 1.
• [9] Genetic inactivation of the Fanconi anemia gene FANCC identified in the hepatocellular carcinoma cell line HuH-7 confers sensitivity towards DNA-interstrand crosslinking agents.Mol Cancer. 2010 May 28;9:127. doi: 10.1186/1476-4598-9-127.
• [10] Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated.J Clin Invest. 2007 May;117(5):1440-9. doi: 10.1172/JCI31245. Epub 2007 Apr 12.
• [11] Associations of complementation group, ALDH2 genotype, and clonal abnormalities with hematological outcome in Japanese patients with Fanconi anemia.Ann Hematol. 2019 Feb;98(2):271-280. doi: 10.1007/s00277-018-3517-0. Epub 2018 Oct 27.
• [12] Targeted disruption of FANCC and FANCG in human cancer provides a preclinical model for specific therapeutic options.Gastroenterology. 2006 Jun;130(7):2145-54. doi: 10.1053/j.gastro.2006.03.016.
• [13] Germ line Fanconi anemia complementation group C mutations and pancreatic cancer.Cancer Res. 2005 Jan 15;65(2):383-6.
• [14] 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.
• [15] Polymorphisms of DNA repair genes and risk of non-small cell lung cancer.Carcinogenesis. 2006 Mar;27(3):560-7. doi: 10.1093/carcin/bgi232. Epub 2005 Sep 29.
• [16] Characterization of arecoline-induced effects on cytotoxicity in normal human gingival fibroblasts by global gene expression profiling. Toxicol Sci. 2007 Nov;100(1):66-74.
• [17] Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis.Brain Res Mol Brain Res. 2003 Nov 26;119(2):170-83. doi: 10.1016/j.molbrainres.2003.09.008.
• [18] 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.
• [19] 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.
• [20] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [21] Exploring pradimicin-IRD antineoplastic mechanisms and related DNA repair pathways. Chem Biol Interact. 2023 Feb 1;371:110342. doi: 10.1016/j.cbi.2023.110342. Epub 2023 Jan 10.
• [22] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [23] Altered ErbB receptor signaling and gene expression in cisplatin-resistant ovarian cancer. Cancer Res. 2005 Aug 1;65(15):6789-800. doi: 10.1158/0008-5472.CAN-04-2684.
• [24] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [25] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [26] 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.
• [27] Comparison of gene expression in HCT116 treatment derivatives generated by two different 5-fluorouracil exposure protocols. Mol Cancer. 2004 Apr 26;3:11.
• [28] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [29] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
• [30] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [31] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [32] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [33] 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.
• [34] Characterization of arecoline-induced effects on cytotoxicity in normal human gingival fibroblasts by global gene expression profiling. Toxicol Sci. 2007 Nov;100(1):66-74.
• [35] 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.
• [36] 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.
• [37] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [38] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [39] In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin Cancer Res. 2005 Oct 15;11(20):7508-15. doi: 10.1158/1078-0432.CCR-05-1048.
• [40] Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde. Cancer Res. 2007 Dec 1;67(23):11117-22. doi: 10.1158/0008-5472.CAN-07-3028.