Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGQSH1Z)

• DOT Name: Forkhead box protein I3 (FOXI3)
• Gene Name: FOXI3
• Related Disease:
  DiGeorge syndrome
  Aural atresia, congenital
• UniProt ID: FOXI3_HUMAN
• Pfam ID: PF00250
• Sequence:
  MALYCGDNFGVYSQPGLPPPAATAAAPGAPPAARAPYGLADYAAPPAAAANPYLWLNGPG
  VGGPPSAAAAAAAAYLGAPPPPPPPGAAAGPFLQPPPAAGTFGCSQRPFAQPAPAAPASP
  AAPAGPGELGWLSMASREDLMKMVRPPYSYSALIAMAIQSAPERKLTLSHIYQFVADSFP
  FYQRSKAGWQNSIRHNLSLNDCFKKVPRDEDDPGKGNYWTLDPNCEKMFDNGNFRRKRKR
  RSEASNGSTVAAGTSKSEEGLSSGLGSGVGGKPEEESPSTLLRPSHSPEPPEGTKSTASS
  PGGPMLTSTPCLNTFFSSLSSLSVSSSVSTQRALPGSRHLGIQGAQLPSSGVFSPTSISE
  ASADTLQLSNSTSNSTGQRSSYYSPFPASTSGGQSSPFSSPFHNFSMVNSLIYPREGSEV
• Function: Transcription factor required for pharyngeal arch development, which is involved in hair, ear, jaw and dental development. May act as a pioneer transcription factor during pharyngeal arch development. Required for epithelial cell differentiation within the epidermis. Acts at multiple stages of otic placode induction: necessary for preplacodal ectoderm to execute an inner ear program. Required for hair follicle stem cell specification. Acts downstream of TBX1 for the formation of the thymus and parathyroid glands from the third pharyngeal pouch.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
DiGeorge syndrome	DIST1RKO	Strong	Biomarker	[1]
Aural atresia, congenital	DISCP7UV	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Forkhead box protein I3 (FOXI3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Forkhead box protein I3 (FOXI3).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Forkhead box protein I3 (FOXI3).	[4]

References

• [1] Recurrent microdeletions at chromosome 2p11.2 are associated with thymic hypoplasia and features resembling DiGeorge syndrome.J Allergy Clin Immunol. 2020 Jan;145(1):358-367.e2. doi: 10.1016/j.jaci.2019.09.020. Epub 2019 Oct 7.
• [2] Congenital aural atresia associated with agenesis of internal carotid artery in a girl with a FOXI3 deletion.Am J Med Genet A. 2015 Mar;167A(3):537-44. doi: 10.1002/ajmg.a.36895. Epub 2015 Feb 5.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] 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.