Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7LLBZ7)

• DOT Name: Forkhead box protein J1 (FOXJ1)
• Synonyms: Forkhead-related protein FKHL13; Hepatocyte nuclear factor 3 forkhead homolog 4; HFH-4
• Gene Name: FOXJ1
• Related Disease:
  Al-Raqad syndrome
  Allergic rhinitis
  Ependymoma
  Advanced cancer
  Asthma
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Bronchiectasis
  Bronchitis
  Ciliary dyskinesia, primary, 43
  Ciliopathy
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Cystic fibrosis
  Hepatocellular carcinoma
  Hydrocephalus
  Nasal polyp
  Neoplasm
  Primary ciliary dyskinesia 1
  Prostate cancer
  Prostate carcinoma
  Rheumatoid arthritis
  Rhinitis
  Systemic lupus erythematosus
  Urinary bladder cancer
  Urinary bladder neoplasm
  Bladder cancer
  Carcinoma
  Gastric cancer
  Laryngeal squamous cell carcinoma
  Stomach cancer
  Primary ciliary dyskinesia
  Stroke
• UniProt ID: FOXJ1_HUMAN
• Pfam ID: PF00250
• Sequence:
  MAESWLRLSGAGPAEEAGPEGGLEEPDALDDSLTSLQWLQEFSILNAKAPALPPGGTDPH
  GYHQVPGSAAPGSPLAADPACLGQPHTPGKPTSSCTSRSAPPGLQAPPPDDVDYATNPHV
  KPPYSYATLICMAMQASKATKITLSAIYKWITDNFCYFRHADPTWQNSIRHNLSLNKCFI
  KVPREKDEPGKGGFWRIDPQYAERLLSGAFKKRRLPPVHIHPAFARQAAQEPSAVPRAGP
  LTVNTEAQQLLREFEEATGEAGWGAGEGRLGHKRKQPLPKRVAKVPRPPSTLLPTPEEQG
  ELEPLKGNFDWEAIFDAGTLGGELGALEALELSPPLSPASHVDVDLTIHGRHIDCPATWG
  PSVEQAADSLDFDETFLATSFLQHPWDESGSGCLPPEPLFEAGDATLASDLQDWASVGAF
  L
• Function: Transcription factor specifically required for the formation of motile cilia. Acts by activating transcription of genes that mediate assembly of motile cilia, such as CFAP157. Binds the DNA consensus sequences 5'-HWDTGTTTGTTTA-3' or 5'-KTTTGTTGTTKTW-3' (where H is not G, W is A or T, D is not C, and K is G or T). Activates the transcription of a variety of ciliary proteins in the developing brain and lung.
• Tissue Specificity: Testis, oviduct, lung and brain cortex.

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Al-Raqad syndrome	DISR2J8Q	Definitive	Genetic Variation	[1]
Allergic rhinitis	DIS3U9HN	Definitive	Altered Expression	[2]
Ependymoma	DISUMRNZ	Definitive	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Asthma	DISW9QNS	Strong	Altered Expression	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Bronchiectasis	DIS5MYEE	Strong	Biomarker	[9]
Bronchitis	DISBM6EQ	Strong	Altered Expression	[10]
Ciliary dyskinesia, primary, 43	DIS0LP95	Strong	Autosomal dominant	[11]
Ciliopathy	DIS10G4I	Strong	Genetic Variation	[12]
Colon cancer	DISVC52G	Strong	Altered Expression	[13]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Hydrocephalus	DISIZUF7	Strong	Genetic Variation	[15]
Nasal polyp	DISLP3XE	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[16]
Primary ciliary dyskinesia 1	DISPGX6H	Strong	GermlineCausalMutation	[15]
Prostate cancer	DISF190Y	Strong	Altered Expression	[17]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[17]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[6]
Rhinitis	DISKLMN7	Strong	Genetic Variation	[18]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[6]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	moderate	Altered Expression	[16]
Carcinoma	DISH9F1N	moderate	Altered Expression	[16]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[19]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[20]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[19]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[15]
Stroke	DISX6UHX	Limited	Biomarker	[21]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Forkhead box protein J1 (FOXJ1) affects the response to substance of Doxorubicin.	[33]

2 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 J1 (FOXJ1).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Forkhead box protein J1 (FOXJ1).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Forkhead box protein J1 (FOXJ1).	[23]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Forkhead box protein J1 (FOXJ1).	[24]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Forkhead box protein J1 (FOXJ1).	[25]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Forkhead box protein J1 (FOXJ1).	[26]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Forkhead box protein J1 (FOXJ1).	[27]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Forkhead box protein J1 (FOXJ1).	[28]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Forkhead box protein J1 (FOXJ1).	[29]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Forkhead box protein J1 (FOXJ1).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Forkhead box protein J1 (FOXJ1).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Forkhead box protein J1 (FOXJ1).	[27]

References

• [1] Novel expression and transcriptional regulation of FoxJ1 during oro-facial morphogenesis.Hum Mol Genet. 2008 Dec 1;17(23):3643-54. doi: 10.1093/hmg/ddn258. Epub 2008 Aug 22.
• [2] Downregulation and Aberrant Localization of Forkhead Box J1 in Allergic Nasal Mucosa.Int Arch Allergy Immunol. 2018;176(2):115-123. doi: 10.1159/000488014. Epub 2018 Apr 10.
• [3] Decreased FOXJ1 expression and its ciliogenesis programme in aggressive ependymoma and choroid plexus tumours.J Pathol. 2016 Mar;238(4):584-97. doi: 10.1002/path.4682.
• [4] FOXJ1 promotes bladder cancer cell growth and regulates Warburg effect.Biochem Biophys Res Commun. 2018 Jan 1;495(1):988-994. doi: 10.1016/j.bbrc.2017.11.063. Epub 2017 Nov 10.
• [5] Aberrant localization of FOXJ1 correlates with the disease severity and comorbidities in patients with nasal polyps.Allergy Asthma Clin Immunol. 2018 Nov 14;14:71. doi: 10.1186/s13223-018-0296-z. eCollection 2018.
• [6] Association of FOXJ1 polymorphisms with systemic lupus erythematosus and rheumatoid arthritis in Korean population.Exp Mol Med. 2007 Dec 31;39(6):805-11. doi: 10.1038/emm.2007.87.
• [7] Expression of FOXJ1 in hepatocellular carcinoma: correlation with patients' prognosis and tumor cell proliferation.Mol Carcinog. 2013 Aug;52(8):647-59. doi: 10.1002/mc.21904. Epub 2012 Apr 4.
• [8] Comparative epigenomics of human and mouse mammary tumors.Genes Chromosomes Cancer. 2009 Jan;48(1):83-97. doi: 10.1002/gcc.20620.
• [9] No deleterious mutations in the FOXJ1 (alias HFH-4) gene in patients with primary ciliary dyskinesia (PCD).Cytogenet Cell Genet. 2000;90(1-2):119-22. doi: 10.1159/000015645.
• [10] Effects of paramyxoviral infection on airway epithelial cell Foxj1 expression, ciliogenesis, and mucociliary function.Am J Pathol. 2001 Dec;159(6):2055-69. doi: 10.1016/S0002-9440(10)63057-X.
• [11] 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.
• [12] Identification of Important Effector Proteins in the FOXJ1 Transcriptional Network Associated With Ciliogenesis and Ciliary Function.Front Genet. 2019 Mar 1;10:23. doi: 10.3389/fgene.2019.00023. eCollection 2019.
• [13] Forkhead Box Protein J1 (FOXJ1) is Overexpressed in Colorectal Cancer and Promotes Nuclear Translocation of -Catenin in SW620 Cells.Med Sci Monit. 2017 Feb 17;23:856-866. doi: 10.12659/msm.902906.
• [14] Expression of CFTR from a ciliated cell-specific promoter is ineffective at correcting nasal potential difference in CF mice.Gene Ther. 2007 Oct;14(20):1492-501. doi: 10.1038/sj.gt.3302994. Epub 2007 Jul 19.
• [15] De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy with Hydrocephalus and Randomization of Left/Right Body Asymmetry. Am J Hum Genet. 2019 Nov 7;105(5):1030-1039. doi: 10.1016/j.ajhg.2019.09.022. Epub 2019 Oct 17.
• [16] The link between FOXJ1 expression level in bladder carcinoma and tumor recurrence.Oncol Lett. 2018 Feb;15(2):1483-1486. doi: 10.3892/ol.2017.7504. Epub 2017 Nov 29.
• [17] Significance of the detection of TIM-3 and FOXJ1 in prostate cancer.J BUON. 2017 Jul-Aug;22(4):1017-1021.
• [18] Identification of single nucleotide polymorphisms in FOXJ1 and their association with allergic rhinitis.J Hum Genet. 2006;51(4):292-297. doi: 10.1007/s10038-006-0359-8. Epub 2006 Mar 4.
• [19] MicroRNA-6852 suppresses cell proliferation and invasion via targeting forkhead box J1 in gastric cancer.Exp Ther Med. 2018 Oct;16(4):3249-3255. doi: 10.3892/etm.2018.6569. Epub 2018 Aug 2.
• [20] Knockdown of FOXJ1 inhibits the proliferation, migration, invasion, and glycolysis in laryngeal squamous cell carcinoma cells.J Cell Biochem. 2019 Sep;120(9):15874-15882. doi: 10.1002/jcb.28858. Epub 2019 May 6.
• [21] Foxj1 expressing ependymal cells do not contribute new cells to sites of injury or stroke in the mouse forebrain.Sci Rep. 2018 Jan 29;8(1):1766. doi: 10.1038/s41598-018-19913-x.
• [22] 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.
• [23] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [24] 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.
• [25] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [26] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [27] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [28] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [29] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [30] 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.
• [31] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [32] 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.
• [33] Prediction of doxorubicin sensitivity in breast tumors based on gene expression profiles of drug-resistant cell lines correlates with patient survival. Oncogene. 2005 Nov 17;24(51):7542-51. doi: 10.1038/sj.onc.1208908.