Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAQSFZ2)

• DOT Name: Fibroblast growth factor 17 (FGF17)
• Synonyms: FGF-17
• Gene Name: FGF17
• Related Disease:
  Benign prostatic hyperplasia
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Dandy-Walker syndrome
  Depression
  Endometrial carcinoma
  Hepatocellular carcinoma
  Hypogonadotropic hypogonadism 20 with or without anosmia
  Hypogonadotropic hypogonadism 7 with or without anosmia
  Klinefelter syndrome
  Metastatic malignant neoplasm
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Hypogonadotropic hypogonadism
  Kallmann syndrome
• UniProt ID: FGF17_HUMAN
• Pfam ID: PF00167
• Sequence:
  MGAARLLPNLTLCLQLLILCCQTQGENHPSPNFNQYVRDQGAMTDQLSRRQIREYQLYSR
  TSGKHVQVTGRRISATAEDGNKFAKLIVETDTFGSRVRIKGAESEKYICMNKRGKLIGKP
  SGKSKDCVFTEIVLENNYTAFQNARHEGWFMAFTRQGRPRQASRSRQNQREAHFIKRLYQ
  GQLPFPNHAEKQKQFEFVGSAPTRRTKRTRRPQPLT
• Function: Plays an important role in the regulation of embryonic development and as signaling molecule in the induction and patterning of the embryonic brain. Required for normal brain development.
• Tissue Specificity: Preferentially expressed in the embryonic brain.
• 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)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Dandy-Walker syndrome	DIS4HC6W	Strong	Genetic Variation	[4]
Depression	DIS3XJ69	Strong	Biomarker	[2]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Hypogonadotropic hypogonadism 20 with or without anosmia	DISFF2IN	Strong	Autosomal dominant	[7]
Hypogonadotropic hypogonadism 7 with or without anosmia	DISPBWEU	Strong	Genetic Variation	[8]
Klinefelter syndrome	DISOUI7W	Strong	Genetic Variation	[8]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Hypogonadotropic hypogonadism	DIS8JSKR	Supportive	Autosomal dominant	[7]
Kallmann syndrome	DISO3HDG	Supportive	Autosomal dominant	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Fibroblast growth factor 17 (FGF17).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Fibroblast growth factor 17 (FGF17).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Fibroblast growth factor 17 (FGF17).	[12]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Fibroblast growth factor 17 (FGF17).	[13]

References

• [1] FGF17 is an autocrine prostatic epithelial growth factor and is upregulated in benign prostatic hyperplasia.Prostate. 2004 Jun 15;60(1):18-24. doi: 10.1002/pros.20026.
• [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] Fibroblast growth factor receptor 4 predicts failure on tamoxifen therapy in patients with recurrent breast cancer.Endocr Relat Cancer. 2008 Mar;15(1):101-11. doi: 10.1677/ERC-07-0080.
• [4] FGF17, a gene involved in cerebellar development, is downregulated in a patient with Dandy-Walker malformation carrying a de novo 8p deletion.Neurogenetics. 2011 Aug;12(3):241-5. doi: 10.1007/s10048-011-0283-8. Epub 2011 Apr 12.
• [5] The fibroblast growth factor 8 family in the female reproductive tract.Reproduction. 2018 Jan;155(1):R53-R62. doi: 10.1530/REP-17-0542.
• [6] Up-regulation of the fibroblast growth factor 8 subfamily in human hepatocellular carcinoma for cell survival and neoangiogenesis.Hepatology. 2011 Mar;53(3):854-64. doi: 10.1002/hep.24099. Epub 2011 Feb 11.
• [7] Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008.
• [8] Genotypic and phenotypic spectra of FGFR1, FGF8, and FGF17 mutations in a Chinese cohort with idiopathic hypogonadotropic hypogonadism.Fertil Steril. 2020 Jan;113(1):158-166. doi: 10.1016/j.fertnstert.2019.08.069. Epub 2019 Nov 17.
• [9] Fibroblast growth factor 17 is over-expressed in human prostate cancer.J Pathol. 2004 Dec;204(5):578-86. doi: 10.1002/path.1668.
• [10] Increased production of human fibroblast growth factor 17 in Escherichia coli and proliferative activity in NIH3T3 cells.Mol Med Rep. 2017 Jul;16(1):447-452. doi: 10.3892/mmr.2017.6575. Epub 2017 May 11.
• [11] 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.
• [12] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [13] 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.
• [14] 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.