Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAW57J4)

DOT Name Forkhead box protein G1 (FOXG1)
Synonyms
Brain factor 1; BF-1; BF1; Brain factor 2; BF-2; BF2; hBF-2; Forkhead box protein G1A; Forkhead box protein G1B; Forkhead box protein G1C; Forkhead-related protein FKHL1; HFK1; Forkhead-related protein FKHL2; HFK2; Forkhead-related protein FKHL3; HFK3
Gene Name FOXG1
Related Disease
FOXG1 disorder ( )
Isolated congenital microcephaly ( )
Rett syndrome, congenital variant ( )
Adult glioblastoma ( )
Advanced cancer ( )
Autism spectrum disorder ( )
Bladder cancer ( )
Cervical cancer ( )
Cervical carcinoma ( )
Choreatic disease ( )
Dilated cardiomyopathy 1A ( )
Epilepsy ( )
Glioma ( )
Intellectual disability ( )
Medulloblastoma ( )
Metastatic malignant neoplasm ( )
Microcephaly ( )
Movement disorder ( )
Neoplasm ( )
Neurodevelopmental disorder ( )
Non-small-cell lung cancer ( )
Rett syndrome ( )
Schizophrenia ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Acrocallosal syndrome ( )
Atypical Rett syndrome ( )
Breast cancer ( )
Breast carcinoma ( )
Epithelial ovarian cancer ( )
Glioblastoma multiforme ( )
Hepatocellular carcinoma ( )
Microlissencephaly ( )
Neurofibromatosis ( )
Neurofibromatosis type 1 ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
West syndrome ( )
Anxiety ( )
Anxiety disorder ( )
Corpus callosum, agenesis of ( )
Cutaneous squamous cell carcinoma ( )
Dystonia ( )
Megalencephaly ( )
Nervous system disease ( )
UniProt ID
FOXG1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
7CBY
Pfam ID
PF00250
Sequence
MLDMGDRKEVKMIPKSSFSINSLVPEAVQNDNHHASHGHHNSHHPQHHHHHHHHHHHPPP
PAPQPPPPPQQQQPPPPPPPAPQPPQTRGAPAADDDKGPQQLLLPPPPPPPPAAALDGAK
ADGLGGKGEPGGGPGELAPVGPDEKEKGAGAGGEEKKGAGEGGKDGEGGKEGEKKNGKYE
KPPFSYNALIMMAIRQSPEKRLTLNGIYEFIMKNFPYYRENKQGWQNSIRHNLSLNKCFV
KVPRHYDDPGKGNYWMLDPSSDDVFIGGTTGKLRRRSTTSRAKLAFKRGARLTSTGLTFM
DRAGSLYWPMSPFLSLHHPRASSTLSYNGTTSAYPSHPMPYSSVLTQNSLGNNHSFSTAN
GLSVDRLVNGEIPYATHHLTAAALAASVPCGLSVPCSGTYSLNPCSVNLLAGQTSYFFPH
VPHPSMTSQSSTSMSARAASSSTSPQAPSTLPCESLRPSLPSFTTGLSGGLSDYFTHQNQ
GSSSNPLIH
Function Transcription repression factor which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon.
Tissue Specificity Expression is restricted to the neurons of the developing telencephalon.
KEGG Pathway
FoxO sig.ling pathway (hsa04068 )
Reactome Pathway
FOXO-mediated transcription of cell cycle genes (R-HSA-9617828 )
Regulation of MECP2 expression and activity (R-HSA-9022692 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
FOXG1 disorder DISL3OYQ Definitive Autosomal dominant [1]
Isolated congenital microcephaly DISUXHZ6 Definitive Biomarker [2]
Rett syndrome, congenital variant DISQTBQI Definitive Autosomal dominant [3]
Adult glioblastoma DISVP4LU Strong Biomarker [4]
Advanced cancer DISAT1Z9 Strong Biomarker [5]
Autism spectrum disorder DISXK8NV Strong Biomarker [6]
Bladder cancer DISUHNM0 Strong Biomarker [7]
Cervical cancer DISFSHPF Strong Biomarker [8]
Cervical carcinoma DIST4S00 Strong Biomarker [8]
Choreatic disease DISH8K3M Strong Genetic Variation [9]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Genetic Variation [10]
Epilepsy DISBB28L Strong Biomarker [11]
Glioma DIS5RPEH Strong Altered Expression [12]
Intellectual disability DISMBNXP Strong Genetic Variation [13]
Medulloblastoma DISZD2ZL Strong Biomarker [14]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [5]
Microcephaly DIS2GRD8 Strong Genetic Variation [15]
Movement disorder DISOJJ2D Strong Biomarker [16]
Neoplasm DISZKGEW Strong Biomarker [17]
Neurodevelopmental disorder DIS372XH Strong Biomarker [18]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [19]
Rett syndrome DISGG5UV Strong Biomarker [20]
Schizophrenia DISSRV2N Strong Altered Expression [21]
Urinary bladder cancer DISDV4T7 Strong Biomarker [7]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [7]
Acrocallosal syndrome DISKMCG2 moderate Biomarker [22]
Atypical Rett syndrome DISWF699 moderate Genetic Variation [23]
Breast cancer DIS7DPX1 moderate Altered Expression [24]
Breast carcinoma DIS2UE88 moderate Altered Expression [24]
Epithelial ovarian cancer DIS56MH2 moderate Altered Expression [25]
Glioblastoma multiforme DISK8246 moderate Biomarker [26]
Hepatocellular carcinoma DIS0J828 moderate Altered Expression [5]
Microlissencephaly DISUCKNT moderate Biomarker [22]
Neurofibromatosis DIS5N2R6 moderate Biomarker [27]
Neurofibromatosis type 1 DIS53JH9 moderate Biomarker [27]
Ovarian cancer DISZJHAP moderate Altered Expression [25]
Ovarian neoplasm DISEAFTY moderate Altered Expression [25]
West syndrome DISLIAU9 moderate Genetic Variation [9]
Anxiety DISIJDBA Limited Biomarker [28]
Anxiety disorder DISBI2BT Limited Biomarker [28]
Corpus callosum, agenesis of DISO9P40 Limited Genetic Variation [29]
Cutaneous squamous cell carcinoma DIS3LXUG Limited Biomarker [30]
Dystonia DISJLFGW Limited Biomarker [31]
Megalencephaly DISYW5SV Limited Biomarker [32]
Nervous system disease DISJ7GGT Limited Biomarker [33]
------------------------------------------------------------------------------------
⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Forkhead box protein G1 (FOXG1). [34]
Triclosan DMZUR4N Approved Triclosan increases the methylation of Forkhead box protein G1 (FOXG1). [36]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Forkhead box protein G1 (FOXG1). [41]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Forkhead box protein G1 (FOXG1). [42]
------------------------------------------------------------------------------------
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Forkhead box protein G1 (FOXG1). [35]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Forkhead box protein G1 (FOXG1). [37]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Forkhead box protein G1 (FOXG1). [38]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Forkhead box protein G1 (FOXG1). [39]
PD-0325901 DM27D4J Phase 2 PD-0325901 decreases the expression of Forkhead box protein G1 (FOXG1). [40]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Forkhead box protein G1 (FOXG1). [39]
Chlorpyrifos DMKPUI6 Investigative Chlorpyrifos decreases the expression of Forkhead box protein G1 (FOXG1). [43]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 Drug(s)

References

1 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.
2 TLE1, a key player in neurogenesis, a new candidate gene for autosomal recessive postnatal microcephaly.Eur J Med Genet. 2018 Dec;61(12):729-732. doi: 10.1016/j.ejmg.2018.05.002. Epub 2018 May 25.
3 FOXG1 is responsible for the congenital variant of Rett syndrome. Am J Hum Genet. 2008 Jul;83(1):89-93. doi: 10.1016/j.ajhg.2008.05.015. Epub 2008 Jun 19.
4 FoxG1 facilitates proliferation and inhibits differentiation by downregulating FoxO/Smad signaling in glioblastoma.Biochem Biophys Res Commun. 2018 Sep 26;504(1):46-53. doi: 10.1016/j.bbrc.2018.08.118. Epub 2018 Aug 29.
5 Forkhead box (FOX) G1 promotes hepatocellular carcinoma epithelial-Mesenchymal transition by activating Wnt signal through forming T-cell factor-4/Beta-catenin/FOXG1 complex.J Exp Clin Cancer Res. 2019 Nov 27;38(1):475. doi: 10.1186/s13046-019-1433-3.
6 FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders.Cell. 2015 Jul 16;162(2):375-390. doi: 10.1016/j.cell.2015.06.034.
7 Forkhead box O-class 1 and forkhead box G1 as prognostic markers for bladder cancer.J Korean Med Sci. 2009 Jun;24(3):468-73. doi: 10.3346/jkms.2009.24.3.468. Epub 2009 Jun 12.
8 MiR-200b promotes the cell proliferation and metastasis of cervical cancer by inhibiting FOXG1.Biomed Pharmacother. 2016 Apr;79:294-301. doi: 10.1016/j.biopha.2016.02.033. Epub 2016 Mar 14.
9 Epilepsy and outcome in FOXG1-related disorders.Epilepsia. 2014 Aug;55(8):1292-300. doi: 10.1111/epi.12648. Epub 2014 May 16.
10 Analyzing gene expression profiles in dilated cardiomyopathy via bioinformatics methods.Braz J Med Biol Res. 2016 Oct 10;49(10):e4897. doi: 10.1590/1414-431X20164897.
11 De novo variants in neurodevelopmental disorders with epilepsy.Nat Genet. 2018 Jul;50(7):1048-1053. doi: 10.1038/s41588-018-0143-7. Epub 2018 Jun 25.
12 FOXG1 Expression Is Elevated in Glioma and Inhibits Glioma Cell Apoptosis.J Cancer. 2018 Feb 11;9(5):778-783. doi: 10.7150/jca.22282. eCollection 2018.
13 Novel FOXG1 mutations in Chinese patients with Rett syndrome or Rett-like mental retardation.BMC Med Genet. 2017 Aug 29;18(1):96. doi: 10.1186/s12881-017-0455-y.
14 FoxG1 interacts with Bmi1 to regulate self-renewal and tumorigenicity of medulloblastoma stem cells.Stem Cells. 2013 Jul;31(7):1266-77. doi: 10.1002/stem.1401.
15 A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders.Genet Med. 2016 Nov;18(11):1090-1096. doi: 10.1038/gim.2016.1. Epub 2016 Mar 3.
16 Early-onset movement disorder as diagnostic marker in genetic syndromes: Three cases of FOXG1-related syndrome.Eur J Paediatr Neurol. 2018 Mar;22(2):336-339. doi: 10.1016/j.ejpn.2018.01.007. Epub 2018 Jan 31.
17 Low FoxG1 and high Olig-2 labelling indices define a prognostically favourable subset in isocitrate dehydrogenase (IDH)-mutant gliomas.Neuropathol Appl Neurobiol. 2018 Feb;44(2):207-223. doi: 10.1111/nan.12447. Epub 2017 Nov 23.
18 The role of FOXG1 in the postnatal development and survival of mouse cochlear hair cells.Neuropharmacology. 2019 Jan;144:43-57. doi: 10.1016/j.neuropharm.2018.10.021. Epub 2018 Oct 15.
19 MiR-378 promotes the cell proliferation of non-small cell lung cancer by inhibiting FOXG1.Eur Rev Med Pharmacol Sci. 2018 Feb;22(4):1011-1019. doi: 10.26355/eurrev_201802_14383.
20 Epilepsy and genetic in Rett syndrome: A review.Brain Behav. 2019 May;9(5):e01250. doi: 10.1002/brb3.1250. Epub 2019 Mar 30.
21 Chromosome conformation elucidates regulatory relationships in developing human brain.Nature. 2016 Oct 27;538(7626):523-527. doi: 10.1038/nature19847. Epub 2016 Oct 19.
22 A 3 Mb deletion in 14q12 causes severe mental retardation, mild facial dysmorphisms and Rett-like features.Am J Med Genet A. 2008 Aug 1;146A(15):1994-8. doi: 10.1002/ajmg.a.32413.
23 FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus.Mol Neurobiol. 2019 Jul;56(7):5188-5201. doi: 10.1007/s12035-018-1444-7. Epub 2018 Dec 11.
24 Transcriptional repression of AIB1 by FoxG1 leads to apoptosis in breast cancer cells.Mol Endocrinol. 2013 Jul;27(7):1113-27. doi: 10.1210/me.2012-1353. Epub 2013 May 9.
25 Overexpression of FOXG1 contributes to TGF-beta resistance through inhibition of p21WAF1/CIP1 expression in ovarian cancer.Br J Cancer. 2009 Oct 20;101(8):1433-43. doi: 10.1038/sj.bjc.6605316. Epub 2009 Sep 15.
26 Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma-initiating cells.Mol Oncol. 2018 Jun;12(6):775-787. doi: 10.1002/1878-0261.12168. Epub 2018 Apr 27.
27 An infant with MLH3 variants, FOXG1-duplication and multiple, benign cranial and spinal tumors: A clinical exome sequencing study.Genes Chromosomes Cancer. 2016 Feb;55(2):131-42. doi: 10.1002/gcc.22319. Epub 2015 Nov 6.
28 Foxg1 deletion impairs the development of the epithalamus.Mol Brain. 2018 Feb 2;11(1):5. doi: 10.1186/s13041-018-0350-2.
29 FOXG1 Orchestrates Neocortical Organization and Cortico-Cortical Connections.Neuron. 2018 Dec 5;100(5):1083-1096.e5. doi: 10.1016/j.neuron.2018.10.016. Epub 2018 Nov 1.
30 miR-30a-5p modulates traits of cutaneous squamous cell carcinoma (cSCC) via forkhead box protein G1 (FOXG1).Neoplasma. 2019 Nov;66(6):908-917. doi: 10.4149/neo_2018_181205N923. Epub 2019 Jun 28.
31 Emerging Monogenic Complex Hyperkinetic Disorders.Curr Neurol Neurosci Rep. 2017 Oct 30;17(12):97. doi: 10.1007/s11910-017-0806-2.
32 Snf2h Drives Chromatin Remodeling to Prime Upper Layer Cortical Neuron Development.Front Mol Neurosci. 2019 Oct 17;12:243. doi: 10.3389/fnmol.2019.00243. eCollection 2019.
33 A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles.Arch Toxicol. 2013 Apr;87(4):721-33. doi: 10.1007/s00204-012-0984-2. Epub 2012 Dec 2.
34 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.
35 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.
36 Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort. Environ Pollut. 2021 Dec 1;290:118024. doi: 10.1016/j.envpol.2021.118024. Epub 2021 Aug 21.
37 5-Fluorouracil inhibits neural differentiation via Mfn1/2 reduction in human induced pluripotent stem cells. J Toxicol Sci. 2018;43(12):727-734. doi: 10.2131/jts.43.727.
38 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
39 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.
40 PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
41 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.
42 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.
43 Chlorpyrifos inhibits neural induction via Mfn1-mediated mitochondrial dysfunction in human induced pluripotent stem cells. Sci Rep. 2017 Jan 23;7:40925. doi: 10.1038/srep40925.