Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT18C29S)

• DOT Name: Follistatin-related protein 5 (FSTL5)
• Synonyms: Follistatin-like protein 5
• Gene Name: FSTL5
• Related Disease:
  Narcolepsy
  Bipolar depression
  Bipolar disorder
  Hepatocellular carcinoma
  Medulloblastoma
  Neoplasm
  Advanced cancer
  Alcohol dependence
  Alcohol-induced disorders
  Alcohol-related disorders
  Acute myelogenous leukaemia
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
• UniProt ID: FSTL5_HUMAN
• Pfam ID: PF13927 ; PF07648
• Sequence:
  MFKCWSVVLVLGFIFLESEGRPTKEGGYGLKSYQPLMRLRHKQEKNQESSRVKGFMIQDG
  PFGSCENKYCGLGRHCVTSRETGQAECACMDLCKRHYKPVCGSDGEFYENHCEVHRAACL
  KKQKITIVHNEDCFFKGDKCKTTEYSKMKNMLLDLQNQKYIMQENENPNGDDISRKKLLV
  DQMFKYFDADSNGLVDINELTQVIKQEELGKDLFDCTLYVLLKYDDFNADKHLALEEFYR
  AFQVIQLSLPEDQKLSITAATVGQSAVLSCAIQGTLRPPIIWKRNNIILNNLDLEDINDF
  GDDGSLYITKVTTTHVGNYTCYADGYEQVYQTHIFQVNVPPVIRVYPESQAREPGVTASL
  RCHAEGIPKPQLGWLKNGIDITPKLSKQLTLQANGSEVHISNVRYEDTGAYTCIAKNEAG
  VDEDISSLFVEDSARKTLANILWREEGLGIGNMFYVFYEDGIKVIQPIECEFQRHIKPSE
  KLLGFQDEVCPKAEGDEVQRCVWASAVNVKDKFIYVAQPTLDRVLIVDVQSQKVVQAVST
  DPVPVKLHYDKSHDQVWVLSWGTLEKTSPTLQVITLASGNVPHHTIHTQPVGKQFDRVDD
  FFIPTTTLIITHMRFGFILHKDEAALQKIDLETMSYIKTINLKDYKCVPQSLAYTHLGGY
  YFIGCKPDSTGAVSPQVMVDGVTDSVIGFNSDVTGTPYVSPDGHYLVSINDVKGLVRVQY
  ITIRGEIQEAFDIYTNLHISDLAFQPSFTEAHQYNIYGSSSTQTDVLFVELSSGKVKMIK
  SLKEPLKAEEWPWNRKNRQIQDSGLFGQYLMTPSKDSLFILDGRLNKLNCEITEVEKGNT
  VIWVGDA

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Narcolepsy	DISLCNLI	Definitive	Genetic Variation	[1]
Bipolar depression	DISA75FU	Strong	Biomarker	[2]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[5]
Alcohol dependence	DIS4ZSCO	moderate	Genetic Variation	[6]
Alcohol-induced disorders	DIS3SFYT	moderate	Genetic Variation	[6]
Alcohol-related disorders	DIS3K4KK	moderate	Genetic Variation	[6]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[7]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[3]
Liver cancer	DISDE4BI	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Follistatin-related protein 5 (FSTL5).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Follistatin-related protein 5 (FSTL5).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Follistatin-related protein 5 (FSTL5).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Follistatin-related protein 5 (FSTL5).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Follistatin-related protein 5 (FSTL5).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Follistatin-related protein 5 (FSTL5).	[13]
Fenfluramine	DM0762O	Phase 3	Fenfluramine increases the expression of Follistatin-related protein 5 (FSTL5).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Follistatin-related protein 5 (FSTL5).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Follistatin-related protein 5 (FSTL5).	[16]

References

• [1] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [2] Genome-wide association study identifies 30 loci associated with bipolar disorder.Nat Genet. 2019 May;51(5):793-803. doi: 10.1038/s41588-019-0397-8. Epub 2019 May 1.
• [3] Follistatin-like protein 5 inhibits hepatocellular carcinoma progression by inducing caspase-dependent apoptosis and regulating Bcl-2 family proteins.J Cell Mol Med. 2018 Dec;22(12):6190-6201. doi: 10.1111/jcmm.13906. Epub 2018 Sep 25.
• [4] FSTL5 is a marker of poor prognosis in non-WNT/non-SHH medulloblastoma.J Clin Oncol. 2011 Oct 10;29(29):3852-61. doi: 10.1200/JCO.2011.36.2798. Epub 2011 Sep 12.
• [5] Down-regulated FSTL5 promotes cell proliferation and survival by affecting Wnt/-catenin signaling in hepatocellular carcinoma.Int J Clin Exp Pathol. 2015 Mar 1;8(3):3386-94. eCollection 2015.
• [6] Ancestry-specific and sex-specific risk alleles identified in a genome-wide gene-by-alcohol dependence interaction study of risky sexual behaviors.Am J Med Genet B Neuropsychiatr Genet. 2017 Dec;174(8):846-853. doi: 10.1002/ajmg.b.32604. Epub 2017 Oct 9.
• [7] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [10] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [11] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [12] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [13] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [14] 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.
• [15] Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle and endothelial cells. Pulm Circ. 2011 Jul-Sep;1(3):405-18. doi: 10.4103/2045-8932.87310.
• [16] 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.