Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6BHWZP)

• DOT Name: Fibroblast growth factor 16 (FGF16)
• Synonyms: FGF-16
• Gene Name: FGF16
• Related Disease:
  Cleft palate
  Diabetic retinopathy
  Hepatocellular carcinoma
  Isolated cleft palate
  Myocardial infarction
  Syndactyly type 8
  Lung cancer
  Lung carcinoma
  Neoplasm
• UniProt ID: FGF16_HUMAN
• Pfam ID: PF00167
• Sequence:
  MAEVGGVFASLDWDLHGFSSSLGNVPLADSPGFLNERLGQIEGKLQRGSPTDFAHLKGIL
  RRRQLYCRTGFHLEIFPNGTVHGTRHDHSRFGILEFISLAVGLISIRGVDSGLYLGMNER
  GELYGSKKLTRECVFREQFEENWYNTYASTLYKHSDSERQYYVALNKDGSPREGYRTKRH
  QKFTHFLPRPVDPSKLPSMSRDLFHYR
• Function: Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation, and is required for normal cardiomyocyte proliferation and heart development.
• 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 FGFR3 (R-HSA-1839130)
  FGFR4 ligand binding and activation (R-HSA-190322)
  FGFR3c ligand binding and activation (R-HSA-190372)
  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-5654221)
  Phospholipase C-mediated cascade (R-HSA-5654227)
  Phospholipase C-mediated cascade (R-HSA-5654228)
  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 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 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

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cleft palate	DIS6G5TF	Strong	Posttranslational Modification	[1]
Diabetic retinopathy	DISHGUJM	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Isolated cleft palate	DISV80CD	Strong	Posttranslational Modification	[1]
Myocardial infarction	DIS655KI	Strong	Biomarker	[4]
Syndactyly type 8	DISKIG0N	Strong	X-linked	[5]
Lung cancer	DISCM4YA	Limited	Biomarker	[6]
Lung carcinoma	DISTR26C	Limited	Biomarker	[6]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Fibroblast growth factor 16 (FGF16).	[7]

2 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 affects the methylation of Fibroblast growth factor 16 (FGF16).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Fibroblast growth factor 16 (FGF16).	[9]

References

• [1] DNA hypermethylation of Fgf16 and Tbx22 associated with cleft palate during palatal fusion.J Appl Oral Sci. 2019 Oct 7;27:e20180649. doi: 10.1590/1678-7757-2018-0649. eCollection 2019.
• [2] MiRNA-144-3p inhibits high glucose induced cell proliferation through suppressing FGF16.Biosci Rep. 2019 Jul 25;39(7):BSR20181788. doi: 10.1042/BSR20181788. Print 2019 Jul 31.
• [3] 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.
• [4] FGF-16 protects against adverse cardiac remodeling in the infarct diabetic heart.Am J Transl Res. 2017 Apr 15;9(4):1630-1640. eCollection 2017.
• [5] Whole exome sequencing identifies FGF16 nonsense mutations as the cause of X-linked recessive metacarpal 4/5 fusion. J Med Genet. 2013 Sep;50(9):579-84. doi: 10.1136/jmedgenet-2013-101659. Epub 2013 May 24.
• [6] High-yield of biologically active recombinant human fibroblast growth factor-16 in E. coli and its mechanism of proliferation in NCL-H460 cells.Prep Biochem Biotechnol. 2017 Aug 9;47(7):720-729. doi: 10.1080/10826068.2017.1315599. Epub 2017 Apr 14.
• [7] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [8] 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.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.