Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJIQ8YZ)

• DOT Name: Fibroblast growth factor 20 (FGF20)
• Synonyms: FGF-20
• Gene Name: FGF20
• Related Disease:
  Advanced cancer
  Bipolar disorder
  Colon cancer
  Colon carcinoma
  Colorectal neoplasm
  Depression
  Hepatocellular carcinoma
  Hypophosphatemic rickets
  Inflammatory bowel disease
  Non-alcoholic fatty liver disease
  Vitamin D-dependent rickets, type 2
  Alopecia
  Autosomal dominant prognathism
  Bilateral renal agenesis
  Parkinsonian disorder
  Renal hypodysplasia/aplasia 2
• UniProt ID: FGF20_HUMAN
• PDB ID: 3F1R
• Pfam ID: PF00167
• Sequence:
  MAPLAEVGGFLGGLEGLGQQVGSHFLLPPAGERPPLLGERRSAAERSARGGPGAAQLAHL
  HGILRRRQLYCRTGFHLQILPDGSVQGTRQDHSLFGILEFISVAVGLVSIRGVDSGLYLG
  MNDKGELYGSEKLTSECIFREQFEENWYNTYSSNIYKHGDTGRRYFVALNKDGTPRDGAR
  SKRHQKFTHFLPRPVDPERVPELYKDLLMYT
• Function: Neurotrophic factor that regulates central nervous development and function.
• Tissue Specificity: Predominantly expressed in the cerebellum.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  Calcium sig.ling pathway (hsa04020)
  PI3K-Akt sig.ling pathway (hsa04151)
  Regulation of actin cytoskeleton (hsa04810)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Melanoma (hsa05218)
  Breast cancer (hsa05224)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  (FGFR2)
  (FGFR3)
  (FGFR4)
  PIP3 activates AKT signaling (R-HSA-1257604)
  Signaling by activated point mutants of FGFR1 (R-HSA-1839122)
  Signaling by activated point mutants of FGFR3 (R-HSA-1839130)
  FGFR4 ligand binding and activation (R-HSA-190322)
  FGFR3b ligand binding and activation (R-HSA-190371)
  FGFR3c ligand binding and activation (R-HSA-190372)
  FGFR1c ligand binding and activation (R-HSA-190373)
  FGFR2c ligand binding and activation (R-HSA-190375)
  Activated point mutants of FGFR2 (R-HSA-2033519)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Phospholipase C-mediated cascade (R-HSA-5654219)
  Phospholipase C-mediated cascade (R-HSA-5654221)
  Phospholipase C-mediated cascade (R-HSA-5654227)
  Phospholipase C-mediated cascade (R-HSA-5654228)
  Downstream signaling of activated FGFR1 (R-HSA-5654687)
  SHC-mediated cascade (R-HSA-5654688)
  PI-3K cascade (R-HSA-5654689)
  FRS-mediated FGFR1 signaling (R-HSA-5654693)
  PI-3K cascade (R-HSA-5654695)
  SHC-mediated cascade (R-HSA-5654699)
  FRS-mediated FGFR2 signaling (R-HSA-5654700)
  SHC-mediated cascade (R-HSA-5654704)
  FRS-mediated FGFR3 signaling (R-HSA-5654706)
  PI-3K cascade (R-HSA-5654710)
  FRS-mediated FGFR4 signaling (R-HSA-5654712)
  SHC-mediated cascade (R-HSA-5654719)
  PI-3K cascade (R-HSA-5654720)
  Negative regulation of FGFR1 signaling (R-HSA-5654726)
  Negative regulation of FGFR2 signaling (R-HSA-5654727)
  Negative regulation of FGFR3 signaling (R-HSA-5654732)
  Negative regulation of FGFR4 signaling (R-HSA-5654733)
  Signaling by FGFR2 in disease (R-HSA-5655253)
  Signaling by FGFR1 in disease (R-HSA-5655302)
  Signaling by FGFR3 in disease (R-HSA-5655332)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  PI3K Cascade (R-HSA-109704)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Altered Expression	[3]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[3]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[4]
Depression	DIS3XJ69	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Hypophosphatemic rickets	DIS7XTW5	Strong	Altered Expression	[6]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[7]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[8]
Vitamin D-dependent rickets, type 2	DISZHFC3	Strong	Altered Expression	[6]
Alopecia	DIS37HU4	moderate	Biomarker	[9]
Autosomal dominant prognathism	DIS2G3FF	moderate	Genetic Variation	[10]
Bilateral renal agenesis	DISOR5IA	Supportive	Autosomal recessive	[11]
Parkinsonian disorder	DISHGY45	Disputed	Altered Expression	[12]
Renal hypodysplasia/aplasia 2	DISI0F2Y	Limited	Autosomal recessive	[11]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dinoprostone	DMTYOPD	Approved	Fibroblast growth factor 20 (FGF20) increases the abundance of Dinoprostone.	[7]

1 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 Fibroblast growth factor 20 (FGF20).	[13]

References

• [1] FGF-20 and DKK1 are transcriptional targets of beta-catenin and FGF-20 is implicated in cancer and development.EMBO J. 2005 Jan 12;24(1):73-84. doi: 10.1038/sj.emboj.7600460. Epub 2004 Dec 9.
• [2] Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer.Mol Psychiatry. 2009 Jun;14(6):563-89. doi: 10.1038/mp.2009.2. Epub 2009 Feb 10.
• [3] Molecular cloning and characterization of human FGF-20 on chromosome 8p21.3-p22.Biochem Biophys Res Commun. 2000 Aug 2;274(2):337-43. doi: 10.1006/bbrc.2000.3142.
• [4] DICKKOPF-4 and -2 genes are upregulated in human colorectal cancer.Cancer Sci. 2009 Oct;100(10):1923-30. doi: 10.1111/j.1349-7006.2009.01272.x. Epub 2009 Jul 2.
• [5] Expression and purification of an FGF9 fusion protein in E. coli, and the effects of the FGF9 subfamily on human hepatocellular carcinoma cell proliferation and migration.Appl Microbiol Biotechnol. 2017 Nov;101(21):7823-7835. doi: 10.1007/s00253-017-8468-1. Epub 2017 Sep 18.
• [6] Molecular pathology of the fibroblast growth factor family.Hum Mutat. 2009 Sep;30(9):1245-55. doi: 10.1002/humu.21067.
• [7] A novel human fibroblast growth factor treats experimental intestinal inflammation. Gastroenterology. 2002 Oct;123(4):1151-62. doi: 10.1053/gast.2002.36041.
• [8] Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.PLoS One. 2015 May 20;10(5):e0124544. doi: 10.1371/journal.pone.0124544. eCollection 2015.
• [9] Sox2 and FGF20 interact to regulate organ of Corti hair cell and supporting cell development in a spatially-graded manner.PLoS Genet. 2019 Jul 5;15(7):e1008254. doi: 10.1371/journal.pgen.1008254. eCollection 2019 Jul.
• [10] Targeted sequencing in FGF/FGFR genes and association analysis of variants for mandibular prognathism.Medicine (Baltimore). 2017 Jun;96(25):e7240. doi: 10.1097/MD.0000000000007240.
• [11] FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Dev Cell. 2012 Jun 12;22(6):1191-207. doi: 10.1016/j.devcel.2012.04.018.
• [12] Manganese exposure: Linking down-regulation of miRNA-7 and miRNA-433 with -synuclein overexpression and risk of idiopathic Parkinson's disease.Toxicol In Vitro. 2018 Feb;46:94-101. doi: 10.1016/j.tiv.2017.10.003. Epub 2017 Oct 3.
• [13] 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.
• [14] A novel human fibroblast growth factor treats experimental intestinal inflammation. Gastroenterology. 2002 Oct;123(4):1151-62. doi: 10.1053/gast.2002.36041.