Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2IV5P4)

• DOT Name: Zinc finger protein 711
• Synonyms: Zinc finger protein 6
• Gene Name: ZNF711
• Related Disease:
  Intellectual disability, X-linked 97
  X-linked complex neurodevelopmental disorder
  Non-syndromic X-linked intellectual disability
• UniProt ID: ZN711_HUMAN
• Pfam ID: PF00096 ; PF04704
• Sequence:
  MDSGGGSLGLHTPDSRMAHTMIMQDFVAGMAGTAHIDGDHIVVSVPEAVLVSDVVTDDGI
  TLDHGLAAEVVHGPDIITETDVVTEGVIVPEAVLEADVAIEEDLEEDDGDHILTSELITE
  TVRVPEQVFVADLVTGPNGHLEHVVQDCVSGVDSPTMVSEEVLVTNSDTETVIQAAGGVP
  GSTVTIKTEDDDDDDVKSTSEDYLMISLDDVGEKLEHMGNTPLKIGSDGSQEDAKEDGFG
  SEVIKVYIFKAEAEDDVEIGGTEIVTESEYTSGHSVAGVLDQSRMQREKMVYMAVKDSSQ
  EEDDIRDERRVSRRYEDCQASGNTLDSALESRSSTAAQYLQICDGINTNKVLKQKAKKRR
  RGETRQWQTAVIIGPDGQPLTVYPCHICTKKFKSRGFLKRHMKNHPDHLMRKKYQCTDCD
  FTTNKKVSFHNHLESHKLINKVDKTHEFTEYTRRYREASPLSSNKLILRDKEPKMHKCKY
  CDYETAEQGLLNRHLLAVHSKNFPHVCVECGKGFRHPSELKKHMRTHTGEKPYQCQYCIF
  RCADQSNLKTHIKSKHGNNLPYKCEHCPQAFGDERELQRHLDLFQGHKTHQCPHCDHKST
  NSSDLKRHIISVHTKDFPHKCEVCDKGFHRPSELKKHSDIHKGRKIHQCRHCDFKTSDPF
  ILSGHILSVHTKDQPLKCKRCKRGFRQQNELKKHMKTHTGRKIYQCEYCEYSTTDASGFK
  RHVISIHTKDYPHRCEFCKKGFRRPSEKNQHIMRHHKEALM
• Function: Transcription regulator required for brain development. Probably acts as a transcription factor that binds to the promoter of target genes and recruits PHF8 histone demethylase, leading to activated expression of genes involved in neuron development, such as KDM5C. May compete with transcription factor ARX for activation of expression of KDM5C.
• Tissue Specificity: Expressed in neural tissues.
• Reactome Pathway: Generic Transcription Pathway (R-HSA-212436)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability, X-linked 97	DISQINN0	Definitive	X-linked recessive	[1]
X-linked complex neurodevelopmental disorder	DISI3QE9	Definitive	X-linked	[2]
Non-syndromic X-linked intellectual disability	DIS71AI3	Supportive	X-linked	[1]

9 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 Zinc finger protein 711.	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Zinc finger protein 711.	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Zinc finger protein 711.	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Zinc finger protein 711.	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Zinc finger protein 711.	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Zinc finger protein 711.	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Zinc finger protein 711.	[9]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Zinc finger protein 711.	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Zinc finger protein 711.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Zinc finger protein 711.	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Zinc finger protein 711.	[12]

References

• [1] A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet. 2009 May;41(5):535-43. doi: 10.1038/ng.367. Epub 2009 Apr 19.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [11] 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.
• [12] 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.
• [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.