Details of Drug Off-Target (DOT)

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

• DOT Name: FERM, ARHGEF and pleckstrin domain-containing protein 2 (FARP2)
• Synonyms: FERM domain-including RhoGEF; FIR; FERM, RhoGEF and pleckstrin domain-containing protein 2; Pleckstrin homology domain-containing family C member 3; PH domain-containing family C member 3
• Gene Name: FARP2
• Related Disease:
  2q37 microdeletion syndrome
  Autism
  Colorectal carcinoma
  Head-neck squamous cell carcinoma
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Juvenile nephropathic cystinosis
  Leigh syndrome
  Nasopharyngeal carcinoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Seasonal affective disorder
  Vitiligo
  Esophageal cancer
  Hepatitis E virus infection
  Non-small-cell lung cancer
  Advanced cancer
  Carcinoma of esophagus
  Diphtheria
  Esophageal squamous cell carcinoma
  Metastatic malignant neoplasm
  Neoplasm of esophagus
  Phenylketonuria
  Small lymphocytic lymphoma
• UniProt ID: FARP2_HUMAN
• Pfam ID: PF08736 ; PF09380 ; PF00373 ; PF09379 ; PF00169 ; PF00621
• Sequence:
  MGEIEGTYRVLQTAGMRLGAQTPVGVSTLEPGQTLLPRMQEKHLHLRVKLLDNTMEIFDI
  EPKCDGQVLLTQVWKRLNLVECDYFGMEFQNTQSYWIWLEPMKPIIRQIRRPKNVVLRLA
  VKFFPPDPGQLQEEYTRYLFALQLKRDLLEERLTCADTTAALLTSHLLQSEIGDYDETLD
  REHLKVNEYLPGQQHCLEKILEFHQKHVGQTPAESDFQVLEIARKLEMYGIRFHMASDRE
  GTKIQLAVSHMGVLVFQGTTKINTFNWSKVRKLSFKRKRFLIKLHPEVHGPYQDTLEFLL
  GSRDECKNFWKICVEYHTFFRLLDQPKPKAKAVFFSRGSSFRYSGRTQKQLVDYFKDSGM
  KRIPYERRHSKTHTSVRALTADLPKQSISFPEGLRTPASPSSANAFYSLSPSTLVPSGLP
  EFKDSSSSLTDPQVSYVKSPAAERRSGAVAGGPDTPSAQPLGPPALQPGPGLSTKSPQPS
  PSSRKSPLSLSPAFQVPLGPAEQGSSPLLSPVLSDAGGAGMDCEEPRHKRVPADEAYFIV
  KEILATERTYLKDLEVITVWFRSAVVKEDAMPATLMTLLFSNIDPIYEFHRGFLREVEQR
  LALWEGPSKAHTKGSHQRIGDILLRNMRQLKEFTSYFQRHDEVLTELEKATKRCKKLEAV
  YKEFELQKVCYLPLNTFLLKPIQRLLHYRLLLRRLCGHYSPGHHDYADCHDALKAITEVT
  TTLQHILIRLENLQKLTELQRDLVGIENLIAPGREFIREGCLHKLTKKGLQQRMFFLFSD
  MLLYTSKGVAGTSHFRIRGLLPLQGMLVEESDNEWSVPHCFTIYAAQKTIVVAASTRLEK
  EKWMLDLNSAIQAAKSGGDTAPALPGRTVCTRPPRSPNEVSLEQESEDDARGVRSSLEGH
  GQHRANTTMHVCWYRNTSVSRADHSAAVENQLSGYLLRKFKNSHGWQKLWVVFTNFCLFF
  YKTHQDDYPLASLPLLGYSVSIPREADGIHKDYVFKLQFKSHVYFFRAESKYTFERWMEV
  IQGASSSAGRAPSIVQDGPQPSSGLEGMVRGKEE
• Function: Functions as a guanine nucleotide exchange factor that activates RAC1. May have relatively low activity. Plays a role in the response to class 3 semaphorins and remodeling of the actin cytoskeleton. Plays a role in TNFSF11-mediated osteoclast differentiation, especially in podosome rearrangement and reorganization of the actin cytoskeleton. Regulates the activation of ITGB3, integrin signaling and cell adhesion.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Adherens junction (hsa04520)
• Reactome Pathway:
  RAC1 GTPase cycle (R-HSA-9013149)
  SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion (R-HSA-399955)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
2q37 microdeletion syndrome	DISZYHCB	Strong	Biomarker	[1]
Autism	DISV4V1Z	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[3]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[6]
Juvenile nephropathic cystinosis	DIS1U9XG	Strong	Genetic Variation	[7]
Leigh syndrome	DISWQU45	Strong	Biomarker	[8]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[11]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[12]
Seasonal affective disorder	DIS908VO	Strong	Biomarker	[13]
Vitiligo	DISR05SL	Strong	Genetic Variation	[14]
Esophageal cancer	DISGB2VN	moderate	Altered Expression	[15]
Hepatitis E virus infection	DIS0TXIR	Disputed	Biomarker	[16]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Biomarker	[17]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[15]
Carcinoma of esophagus	DISS6G4D	Limited	Biomarker	[18]
Diphtheria	DISZWM55	Limited	Biomarker	[19]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Biomarker	[20]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[15]
Neoplasm of esophagus	DISOLKAQ	Limited	Biomarker	[18]
Phenylketonuria	DISCU56J	Limited	Genetic Variation	[21]
Small lymphocytic lymphoma	DIS30POX	Limited	Genetic Variation	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 2 (FARP2).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 2 (FARP2).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 2 (FARP2).	[25]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 2 (FARP2).	[26]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 2 (FARP2).	[27]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 2 (FARP2).	[28]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 2 (FARP2).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 2 (FARP2).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 2 (FARP2).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of FERM, ARHGEF and pleckstrin domain-containing protein 2 (FARP2).	[31]

References

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• [4] Efficacy of hepatitis B virus ribonuclease H inhibitors, a new class of replication antagonists, in FRG human liver chimeric mice.Antiviral Res. 2018 Jan;149:41-47. doi: 10.1016/j.antiviral.2017.11.008. Epub 2017 Nov 10.
• [5] Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles Produced in a Humanized Liver Mouse Model.J Biol Chem. 2015 Sep 18;290(38):23173-87. doi: 10.1074/jbc.M115.662999. Epub 2015 Jul 29.
• [6] Overexpression of far upstream element (FUSE) binding protein (FBP)-interacting repressor (FIR) supports growth of hepatocellular carcinoma.Hepatology. 2014 Oct;60(4):1241-50. doi: 10.1002/hep.27218. Epub 2014 Jul 31.
• [7] Cystinosis in the Federal Republic of Germany. Coordination and analysis of the data.J Inherit Metab Dis. 1985;8(1):2-4. doi: 10.1007/BF01805472.
• [8] Complete Plasmodium falciparum liver-stage development in liver-chimeric mice.J Clin Invest. 2012 Oct;122(10):3618-28. doi: 10.1172/JCI62684. Epub 2012 Sep 10.
• [9] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.Nat Genet. 2010 Jul;42(7):599-603. doi: 10.1038/ng.601. Epub 2010 May 30.
• [10] Knockdown of Anillin Actin Binding Protein Blocks Cytokinesis in Hepatocytes and Reduces Liver Tumor Development in Mice Without Affecting Regeneration.Gastroenterology. 2018 Apr;154(5):1421-1434. doi: 10.1053/j.gastro.2017.12.013. Epub 2017 Dec 21.
• [11] Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.Nat Genet. 2013 Apr;45(4):385-91, 391e1-2. doi: 10.1038/ng.2560.
• [12] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
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• [14] Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.Nat Genet. 2016 Nov;48(11):1418-1424. doi: 10.1038/ng.3680. Epub 2016 Oct 10.
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• [16] Transmission of hepatitis E virus infection to human-liver chimeric FRG mice using patient plasma.Antiviral Res. 2017 May;141:150-154. doi: 10.1016/j.antiviral.2017.02.011. Epub 2017 Feb 21.
• [17] Baseline tumor size and survival outcomes in lung cancer patients treated with immune checkpoint inhibitors.Semin Oncol. 2019 Aug-Oct;46(4-5):380-384. doi: 10.1053/j.seminoncol.2019.10.002. Epub 2019 Nov 6.
• [18] Adenovirus-mediated FIR demonstrated TP53-independent cell-killing effect and enhanced antitumor activity of carbon-ion beams.Gene Ther. 2016 Jan;23(1):50-6. doi: 10.1038/gt.2015.84. Epub 2015 Aug 4.
• [19] Epidemiology of diphtheria: polypeptide and restriction enzyme analysis in comparison with conventional phage typing.Eur J Clin Microbiol Infect Dis. 1988 Apr;7(2):232-7. doi: 10.1007/BF01963094.
• [20] Anti-FIRexon2, a splicing variant form of PUF60, autoantibody is detected in the sera of esophageal squamous cell carcinoma.Cancer Sci. 2019 Jun;110(6):2004-2013. doi: 10.1111/cas.14024. Epub 2019 May 20.
• [21] Ethnic distribution of phenylketonuria in the north German population.Hum Genet. 1984;65(4):396-9. doi: 10.1007/BF00291566.
• [22] Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.Nat Genet. 2013 Aug;45(8):868-76. doi: 10.1038/ng.2652. Epub 2013 Jun 16.
• [23] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
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• [25] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [26] 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.
• [27] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [30] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [31] 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.
• [32] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.