Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU4TXIW)

• DOT Name: Fez family zinc finger protein 2 (FEZF2)
• Synonyms: Forebrain embryonic zinc finger-like protein 2; Zinc finger protein 312; Zinc finger protein Fez-like
• Gene Name: FEZF2
• Related Disease:
  Adult glioblastoma
  Adult T-cell leukemia/lymphoma
  Autism spectrum disorder
  Bladder cancer
  Colorectal carcinoma
  Glioblastoma multiforme
  Neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
  Isolated congenital microcephaly
  Nasopharyngeal carcinoma
  Tetralogy of fallot
  Non-small-cell lung cancer
• UniProt ID: FEZF2_HUMAN
• Pfam ID: PF00096 ; PF13912
• Sequence:
  MASSASLETMVPPACPRAGASPATSKTLAFSIERIMAKTSEPRAPFEPRPGALEADGSQG
  KKLLNLCSPLPCMIPLQPLGYEVPSKTLLSYSELWKSSLRAGGGGGGGGGGGGGGGGAPV
  CGASGLCKTNCGVCCKAELGLAPSALPAGRVIKPQVINQAVGLPASGSLYYFNYLDSTAY
  PPSELLSGHLFPSGLLNAQAPAALAAHPKLFLLENAKLAGLAADKFPHPAPYPHKERLPA
  PLEQVLKENSALTAERGGVKGHSKLPGGSADGKPKNFTCEVCGKVFNAHYNLTRHMPVHT
  GARPFVCKVCGKGFRQASTLCRHKIIHTQEKPHKCNQCGKAFNRSSTLNTHIRIHAGYKP
  FVCEFCGKGFHQKGNYKNHKLTHSGEKQYKCTICNKAFHQVYNLTFHMHTHNDKKPFTCA
  TCGKGFCRNFDLKKHVRKLHDSVGPAAPSAKDLTRTVQS
• Function: Transcription repressor. Required for the specification of corticospinal motor neurons and other subcerebral projection neurons. May play a role in layer and neuronal subtype-specific patterning of subcortical projections and axonal fasciculation. Controls the development of dendritic arborization and spines of large layer V pyramidal neurons. May be involved in innate immunity.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[5]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Isolated congenital microcephaly	DISUXHZ6	moderate	Altered Expression	[6]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Posttranslational Modification	[7]
Tetralogy of fallot	DISMHFNW	moderate	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Fez family zinc finger protein 2 (FEZF2).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fez family zinc finger protein 2 (FEZF2).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Fez family zinc finger protein 2 (FEZF2).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Fez family zinc finger protein 2 (FEZF2).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Fez family zinc finger protein 2 (FEZF2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Fez family zinc finger protein 2 (FEZF2).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Fez family zinc finger protein 2 (FEZF2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fez family zinc finger protein 2 (FEZF2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Fez family zinc finger protein 2 (FEZF2).	[15]

References

• [1] Assessment of ApoC1, LuzP6, C12orf75 and OCC-1 in cystic glioblastoma using MALDI-TOF mass spectrometry, immunohistochemistry and qRT-PCR.Med Mol Morphol. 2019 Dec;52(4):217-225. doi: 10.1007/s00795-019-00223-8. Epub 2019 Apr 20.
• [2] Evidence for the chronic in vivo production of human T cell leukemia virus type I Rof and Tof proteins from cytotoxic T lymphocytes directed against viral peptides.J Exp Med. 2000 Feb 7;191(3):567-72. doi: 10.1084/jem.191.3.567.
• [3] Transcriptional dysregulation of neocortical circuit assembly in ASD.Int Rev Neurobiol. 2013;113:167-205. doi: 10.1016/B978-0-12-418700-9.00006-X.
• [4] Loss of Fezf2 promotes malignant progression of bladder cancer by regulating the NF-B signaling pathway.Lab Invest. 2018 Sep;98(9):1225-1236. doi: 10.1038/s41374-018-0077-9. Epub 2018 Jun 20.
• [5] Long noncoding RNA FEZF1-AS1 in human cancers.Clin Chim Acta. 2019 Oct;497:20-26. doi: 10.1016/j.cca.2019.07.004. Epub 2019 Jul 2.
• [6] Genomic selection identifies vertebrate transcription factor Fezf2 binding sites and target genes.J Biol Chem. 2011 May 27;286(21):18641-9. doi: 10.1074/jbc.M111.236471. Epub 2011 Apr 6.
• [7] FEZF2, a novel 3p14 tumor suppressor gene, represses oncogene EZH2 and MDM2 expression and is frequently methylated in nasopharyngeal carcinoma.Carcinogenesis. 2013 Sep;34(9):1984-93. doi: 10.1093/carcin/bgt165. Epub 2013 May 14.
• [8] Mutational and functional analysis of the BVES gene coding region in Chinese patients with non-syndromic tetralogy of Fallot.Int J Mol Med. 2013 Apr;31(4):899-903. doi: 10.3892/ijmm.2013.1275. Epub 2013 Feb 7.
• [9] Translating biomarkers into clinical practice: prognostic implications of cyclophilin A and macrophage migratory inhibitory factor identified from protein expression profiles in non-small cell lung cancer.Lung Cancer. 2004 Dec;46(3):313-23. doi: 10.1016/j.lungcan.2004.05.013.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [12] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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.
• [15] 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.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.