Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXYV6GO)

DOT Name Forkhead box protein D3 (FOXD3)
Synonyms HNF3/FH transcription factor genesis
Gene Name FOXD3
Related Disease
Colon cancer ( )
Colon carcinoma ( )
Acute coronary syndrome ( )
Advanced cancer ( )
Autoimmune disease ( )
Bacteremia ( )
Breast cancer ( )
Breast carcinoma ( )
Colon polyp ( )
Colorectal carcinoma ( )
Disorder of orbital region ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Endometriosis ( )
Epilepsy ( )
Gastric cancer ( )
Gastric neoplasm ( )
Hashimoto thyroiditis ( )
Hepatocellular carcinoma ( )
Lung adenocarcinoma ( )
Major depressive disorder ( )
Mixed anxiety and depressive disorder ( )
Neuroblastoma ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Peters anomaly ( )
Stomach cancer ( )
Thyroid gland undifferentiated (anaplastic) carcinoma ( )
Type-1 diabetes ( )
Vitiligo ( )
Zika virus infection ( )
Chronic renal failure ( )
End-stage renal disease ( )
Goiter ( )
Graves disease ( )
Hereditary breast carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Nephropathy ( )
Plasma cell myeloma ( )
Small lymphocytic lymphoma ( )
Aniridia ( )
Glaucoma/ocular hypertension ( )
Melanoma ( )
Metastatic melanoma ( )
Type-1/2 diabetes ( )
UniProt ID
FOXD3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00250
Sequence
MTLSGGGSASDMSGQTVLTAEDVDIDVVGEGDDGLEEKDSDAGCDSPAGPPELRLDEADE
VPPAAPHHGQPQPPHQQPLTLPKEAAGAGAGPGGDVGAPEADGCKGGVGGEEGGASGGGP
GAGSGSAGGLAPSKPKNSLVKPPYSYIALITMAILQSPQKKLTLSGICEFISNRFPYYRE
KFPAWQNSIRHNLSLNDCFVKIPREPGNPGKGNYWTLDPQSEDMFDNGSFLRRRKRFKRH
QQEHLREQTALMMQSFGAYSLAAAAGAAGPYGRPYGLHPAAAAGAYSHPAAAAAAAAAAA
LQYPYALPPVAPVLPPAVPLLPSGELGRKAAAFGSQLGPGLQLQLNSLGAAAAAAGTAGA
AGTTASLIKSEPSARPSFSIENIIGGGPAAPGGSAVGAGVAGGTGGSGGGSTAQSFLRPP
GTVQSAALMATHQPLSLSRTTATIAPILSVPLSGQFLQPAASAAAAAAAAAQAKWPAQ
Function
Binds to the consensus sequence 5'-A[AT]T[AG]TTTGTTT-3' and acts as a transcriptional repressor. Also acts as a transcriptional activator. Negatively regulates transcription of transcriptional repressor RHIT/ZNF205. Promotes development of neural crest cells from neural tube progenitors. Restricts neural progenitor cells to the neural crest lineage while suppressing interneuron differentiation. Required for maintenance of pluripotent cells in the pre-implantation and peri-implantation stages of embryogenesis.
Tissue Specificity Expressed in chronic myeloid leukemia, Jurkat T-cell leukemia and teratocarcinoma cell lines, but not in any other cell lines or normal tissues examined.
Reactome Pathway
POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation (R-HSA-2892247 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colon cancer DISVC52G Definitive Biomarker [1]
Colon carcinoma DISJYKUO Definitive Biomarker [1]
Acute coronary syndrome DIS7DYEW Strong Biomarker [2]
Advanced cancer DISAT1Z9 Strong Altered Expression [1]
Autoimmune disease DISORMTM Strong Genetic Variation [3]
Bacteremia DIS6N9RZ Strong Biomarker [4]
Breast cancer DIS7DPX1 Strong Biomarker [5]
Breast carcinoma DIS2UE88 Strong Biomarker [5]
Colon polyp DIS7V594 Strong Genetic Variation [6]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [7]
Disorder of orbital region DISH0ECJ Strong Altered Expression [8]
Endometrial cancer DISW0LMR Strong Biomarker [9]
Endometrial carcinoma DISXR5CY Strong Biomarker [9]
Endometriosis DISX1AG8 Strong Altered Expression [9]
Epilepsy DISBB28L Strong Biomarker [10]
Gastric cancer DISXGOUK Strong Posttranslational Modification [11]
Gastric neoplasm DISOKN4Y Strong Posttranslational Modification [11]
Hashimoto thyroiditis DIS77CDF Strong Altered Expression [3]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [12]
Lung adenocarcinoma DISD51WR Strong Altered Expression [13]
Major depressive disorder DIS4CL3X Strong Biomarker [14]
Mixed anxiety and depressive disorder DISV809X Strong Genetic Variation [15]
Neuroblastoma DISVZBI4 Strong Biomarker [16]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [17]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [18]
Peters anomaly DISERK0M Strong Biomarker [8]
Stomach cancer DISKIJSX Strong Posttranslational Modification [11]
Thyroid gland undifferentiated (anaplastic) carcinoma DISYBB1W Strong Altered Expression [19]
Type-1 diabetes DIS7HLUB Strong Biomarker [20]
Vitiligo DISR05SL Strong Genetic Variation [3]
Zika virus infection DISQUCTY Strong Biomarker [21]
Chronic renal failure DISGG7K6 moderate Biomarker [22]
End-stage renal disease DISXA7GG moderate Biomarker [22]
Goiter DISLCGI6 moderate Altered Expression [3]
Graves disease DISU4KOQ moderate Altered Expression [3]
Hereditary breast carcinoma DISAEZT5 moderate Genetic Variation [23]
Lung cancer DISCM4YA moderate Biomarker [24]
Lung carcinoma DISTR26C moderate Biomarker [24]
Nephropathy DISXWP4P moderate Biomarker [22]
Plasma cell myeloma DIS0DFZ0 moderate Biomarker [25]
Small lymphocytic lymphoma DIS30POX moderate Altered Expression [26]
Aniridia DIS1P333 Disputed Autosomal dominant [27]
Glaucoma/ocular hypertension DISLBXBY Limited Biomarker [28]
Melanoma DIS1RRCY Limited Biomarker [29]
Metastatic melanoma DISSL43L Limited Biomarker [30]
Type-1/2 diabetes DISIUHAP Limited Genetic Variation [31]
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⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 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 Forkhead box protein D3 (FOXD3). [32]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Forkhead box protein D3 (FOXD3). [33]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Forkhead box protein D3 (FOXD3). [35]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Forkhead box protein D3 (FOXD3). [35]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Forkhead box protein D3 (FOXD3). [35]
Belinostat DM6OC53 Phase 2 Belinostat increases the expression of Forkhead box protein D3 (FOXD3). [35]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Forkhead box protein D3 (FOXD3). [37]
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⏷ Show the Full List of 7 Drug(s)
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 D3 (FOXD3). [34]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Forkhead box protein D3 (FOXD3). [36]
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References

1 FOXD3 is a tumor suppressor of colon cancer by inhibiting EGFR-Ras-Raf-MEK-ERK signal pathway.Oncotarget. 2017 Jan 17;8(3):5048-5056. doi: 10.18632/oncotarget.13790.
2 Prolonged hypothalamic-pituitary-adrenal axis activation after acute coronary syndrome in the GENESIS-PRAXY cohort.Eur J Prev Cardiol. 2018 Jan;25(1):65-72. doi: 10.1177/2047487317734323. Epub 2017 Oct 3.
3 A novel FoxD3 Variant Is Associated With Vitiligo and Elevated Thyroid Auto-Antibodies.J Clin Endocrinol Metab. 2015 Oct;100(10):E1335-42. doi: 10.1210/jc.2015-2126. Epub 2015 Aug 12.
4 Next-generation sequencing diagnostics of bacteremia in sepsis (Next GeneSiS-Trial): Study protocol of a prospective, observational, noninterventional, multicenter, clinical trial.Medicine (Baltimore). 2018 Feb;97(6):e9868. doi: 10.1097/MD.0000000000009868.
5 Methylomics of breast cancer: Seeking epimarkers in peripheral blood of young subjects. Tumour Biol. 2017 Mar;39(3):1010428317695040.
6 Genetic Biopsy for Prediction of Surveillance Intervals after Endoscopic Resection of Colonic Polyps: Results of the GENESIS Study.United European Gastroenterol J. 2018 Mar;6(2):290-299. doi: 10.1177/2050640617723810. Epub 2017 Jul 28.
7 FOXD3, frequently methylated in colorectal cancer, acts as a tumor suppressor and induces tumor cell apoptosis under ER stress via p53.Carcinogenesis. 2020 Sep 24;41(9):1253-1262. doi: 10.1093/carcin/bgz198.
8 Analysis of FOXD3 sequence variation in human ocular disease.Mol Vis. 2012;18:1740-9. Epub 2012 Jun 27.
9 In silico, in vitro and in vivo analysis identifies a potential role for steroid hormone regulation of FOXD3 in endometriosis-associated genes.Hum Reprod. 2016 Feb;31(2):345-54. doi: 10.1093/humrep/dev307. Epub 2015 Dec 23.
10 FOXD3 inhibits SCN2A gene transcription in intractable epilepsy cell models.Exp Neurol. 2018 Apr;302:14-21. doi: 10.1016/j.expneurol.2017.12.012. Epub 2017 Dec 28.
11 Helicobacter pylori causes epigenetic dysregulation of FOXD3 to promote gastric carcinogenesis.Gastroenterology. 2013 Jan;144(1):122-133.e9. doi: 10.1053/j.gastro.2012.10.002. Epub 2012 Oct 8.
12 miR?25?p promotes cell proliferation, migration and invasion by directly targeting FOXD3 in hepatocellular carcinoma cells.Mol Med Rep. 2019 Aug;20(2):1883-1892. doi: 10.3892/mmr.2019.10427. Epub 2019 Jun 26.
13 Tumor suppression function of FoxD3 in lung cancer.Ir J Med Sci. 2016 Aug;185(3):547-553. doi: 10.1007/s11845-015-1297-2. Epub 2015 Apr 17.
14 Gene expression profiling in postmortem prefrontal cortex of major depressive disorder.J Neurosci. 2007 Nov 28;27(48):13329-40. doi: 10.1523/JNEUROSCI.4083-07.2007.
15 Life events and depression in a community sample of siblings.Psychol Med. 2001 Apr;31(3):401-10. doi: 10.1017/s0033291701003361.
16 Risk-Associated Long Noncoding RNA FOXD3-AS1 Inhibits Neuroblastoma Progression by Repressing PARP1-Mediated Activation of CTCF.Mol Ther. 2018 Mar 7;26(3):755-773. doi: 10.1016/j.ymthe.2017.12.017. Epub 2017 Dec 22.
17 Plasma Copeptin and Risk of Lower-Extremity Amputation in Type 1 and Type 2 Diabetes.Diabetes Care. 2019 Dec;42(12):2290-2297. doi: 10.2337/dc19-1062. Epub 2019 Oct 3.
18 Serum Fork-Head Box D3 (FOXD3) Expression Is Down-Regulated in and Associated with Diagnosis of Patients with Non-Small Cell Lung Cancer.Med Sci Monit. 2018 Dec 31;24:9504-9508. doi: 10.12659/MSM.896748.
19 FOXD3 regulates anaplastic thyroid cancer progression.Oncotarget. 2017 May 16;8(20):33644-33651. doi: 10.18632/oncotarget.16853.
20 Plasma concentrations of 8-hydroxy-2'-deoxyguanosine and risk of kidney disease and death in individuals with type 1 diabetes.Diabetologia. 2018 Apr;61(4):977-984. doi: 10.1007/s00125-017-4510-1. Epub 2017 Nov 28.
21 Zika virus induces abnormal cranial osteogenesis by negatively affecting cranial neural crest development.Infect Genet Evol. 2019 Apr;69:176-189. doi: 10.1016/j.meegid.2019.01.023. Epub 2019 Jan 19.
22 Allelic variations in the CYBA gene of NADPH oxidase and risk of kidney complications in patients with type 1 diabetes.Free Radic Biol Med. 2015 Sep;86:16-24. doi: 10.1016/j.freeradbiomed.2015.04.002. Epub 2015 Apr 8.
23 Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing.Int J Cancer. 2019 Apr 15;144(8):1962-1974. doi: 10.1002/ijc.31921. Epub 2018 Nov 13.
24 FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5.Stem Cells. 2019 May;37(5):582-592. doi: 10.1002/stem.2984. Epub 2019 Mar 12.
25 GENESIS: Phase III trial evaluating BL-8040+G-CSF to mobilize hematopoietic cells for autologous transplant in myeloma.Future Oncol. 2019 Nov;15(31):3555-3563. doi: 10.2217/fon-2019-0380. Epub 2019 Sep 9.
26 Epigenetic alterations in a murine model for chronic lymphocytic leukemia.Cell Cycle. 2009 Nov 15;8(22):3663-7. doi: 10.4161/cc.8.22.9957.
27 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.
28 Integrated microarray analysis provided novel insights to the pathogenesis of glaucoma.Mol Med Rep. 2017 Dec;16(6):8735-8746. doi: 10.3892/mmr.2017.7711. Epub 2017 Oct 4.
29 FOXD3 Promotes PAX3 Expression in Melanoma Cells.J Cell Biochem. 2016 Feb;117(2):533-41. doi: 10.1002/jcb.25306. Epub 2015 Sep 1.
30 FOXD3 modulates migration through direct transcriptional repression of TWIST1 in melanoma.Mol Cancer Res. 2014 Sep;12(9):1314-23. doi: 10.1158/1541-7786.MCR-14-0170. Epub 2014 Jul 24.
31 Plasma extracellular superoxide dismutase concentration, allelic variations in the SOD3 gene and risk of myocardial infarction and all-cause mortality in people with type 1 and type 2 diabetes.Cardiovasc Diabetol. 2015 Jan 15;14:845. doi: 10.1186/s12933-014-0163-2.
32 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
33 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
34 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.
35 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.
36 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.
37 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.