Details of Drug Off-Target (DOT)

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

• DOT Name: Juxtaposed with another zinc finger protein 1 (JAZF1)
• Synonyms: TAK1-interacting protein 27; Zinc finger protein 802
• Gene Name: JAZF1
• Related Disease:
  Dedifferentiated liposarcoma
  Thyroid gland papillary carcinoma
  Advanced cancer
  Autoimmune disease
  Colon cancer
  Colon carcinoma
  Endometrial carcinoma
  Fatty liver disease
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Malignant soft tissue neoplasm
  Multiple sclerosis
  Neoplasm
  Non-alcoholic fatty liver disease
  Ovarian neoplasm
  Psoriasis
  Rheumatoid arthritis
  Sarcoma
  Systemic sclerosis
  Allergic rhinitis
  Coronary atherosclerosis
  Moyamoya disease
  Myocardial ischemia
  Ankylosing spondylitis
  Asthma
  Chromosomal disorder
  Crohn disease
  Endometrial cancer
  Endometrium neoplasm
  Eosinophilic esophagitis
  Gastric cancer
  Gout
  Neoplasm of esophagus
  Prostate neoplasm
  Sclerosing cholangitis
  Stomach cancer
  Ulcerative colitis
• UniProt ID: JAZF1_HUMAN
• Sequence:
  MTGIAAASFFSNTCRFGGCGLHFPTLADLIEHIEDNHIDTDPRVLEKQELQQPTYVALSY
  INRFMTDAARREQESLKKKIQPKLSLTLSSSVSRGNVSTPPRHSSGSLTPPVTPPITPSS
  SFRSSTPTGSEYDEEEVDYEESDSDESWTTESAISSEAILSSMCMNGGEEKPFACPVPGC
  KKRYKNVNGIKYHAKNGHRTQIRVRKPFKCRCGKSYKTAQGLRHHTINFHPPVSAEIIRK
  MQQ
• Function: Acts as a transcriptional corepressor of orphan nuclear receptor NR2C2. Inhibits expression of the gluconeogenesis enzyme PCK2 through inhibition of NR2C2 activity. Also involved in transcriptional activation of NAMPT by promoting expression of PPARA and PPARD. Plays a role in lipid metabolism by suppressing lipogenesis, increasing lipolysis and decreasing lipid accumulation in adipose tissue. Plays a role in glucose homeostasis by improving glucose metabolism and insulin sensitivity.
• Tissue Specificity: Highest expression in testis with moderate levels in colon, placenta, prostate and ovary and low levels in brain, spleen, liver and small intestine.

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dedifferentiated liposarcoma	DISYJUCJ	Definitive	Altered Expression	[1]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[4]
Colon cancer	DISVC52G	Strong	Genetic Variation	[5]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[5]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[6]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[8]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[9]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Genetic Variation	[10]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[11]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[12]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[7]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[13]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[14]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[15]
Sarcoma	DISZDG3U	Strong	Genetic Variation	[10]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[4]
Allergic rhinitis	DIS3U9HN	moderate	Genetic Variation	[16]
Coronary atherosclerosis	DISKNDYU	moderate	Altered Expression	[17]
Moyamoya disease	DISO62CA	moderate	Genetic Variation	[18]
Myocardial ischemia	DISFTVXF	moderate	Altered Expression	[17]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[19]
Asthma	DISW9QNS	Limited	Genetic Variation	[20]
Chromosomal disorder	DISM5BB5	Limited	Genetic Variation	[21]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[19]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[6]
Endometrium neoplasm	DIS6OS2L	Limited	Biomarker	[6]
Eosinophilic esophagitis	DISR8WSB	Limited	Genetic Variation	[22]
Gastric cancer	DISXGOUK	Limited	Biomarker	[23]
Gout	DISHC0U7	Limited	Genetic Variation	[24]
Neoplasm of esophagus	DISOLKAQ	Limited	Genetic Variation	[25]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[6]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[19]
Stomach cancer	DISKIJSX	Limited	Biomarker	[23]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Juxtaposed with another zinc finger protein 1 (JAZF1) increases the Metabolic disorder ADR of Chlorothiazide.	[36]

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 Juxtaposed with another zinc finger protein 1 (JAZF1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Juxtaposed with another zinc finger protein 1 (JAZF1).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Juxtaposed with another zinc finger protein 1 (JAZF1).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Juxtaposed with another zinc finger protein 1 (JAZF1).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Juxtaposed with another zinc finger protein 1 (JAZF1).	[29]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Juxtaposed with another zinc finger protein 1 (JAZF1).	[30]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Juxtaposed with another zinc finger protein 1 (JAZF1).	[31]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Juxtaposed with another zinc finger protein 1 (JAZF1).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Juxtaposed with another zinc finger protein 1 (JAZF1).	[32]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Juxtaposed with another zinc finger protein 1 (JAZF1).	[34]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Juxtaposed with another zinc finger protein 1 (JAZF1).	[35]

References

• [1] Analysis of MDM2 Amplification in 43 Endometrial Stromal Tumors: A Potential Diagnostic Pitfall.Int J Gynecol Pathol. 2015 Nov;34(6):576-83. doi: 10.1097/PGP.0000000000000187.
• [2] JAZF1 Suppresses Papillary Thyroid Carcinoma Cell Proliferation and Facilitates Apoptosis via Regulating TAK1/NF-B Pathways.Onco Targets Ther. 2019 Dec 2;12:10501-10514. doi: 10.2147/OTT.S230597. eCollection 2019.
• [3] Refining the prostate cancer genetic association within the JAZF1 gene on chromosome 7p15.2.Cancer Epidemiol Biomarkers Prev. 2010 May;19(5):1349-55. doi: 10.1158/1055-9965.EPI-09-1181. Epub 2010 Apr 20.
• [4] A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.Hum Mol Genet. 2013 Oct 1;22(19):4021-9. doi: 10.1093/hmg/ddt248. Epub 2013 Jun 4.
• [5] Comprehensive genomic analyses of a metastatic colon cancer to the lung by whole exome sequencing and gene expression analysis.Int J Oncol. 2014 Jan;44(1):211-21. doi: 10.3892/ijo.2013.2150. Epub 2013 Oct 25.
• [6] Multiple loci identified in a genome-wide association study of prostate cancer.Nat Genet. 2008 Mar;40(3):310-5. doi: 10.1038/ng.91. Epub 2008 Feb 10.
• [7] JAZF1 ameliorates age and diet-associated hepatic steatosis through SREBP-1c -dependent mechanism.Cell Death Dis. 2018 Aug 28;9(9):859. doi: 10.1038/s41419-018-0923-0.
• [8] The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus.J Gastroenterol. 2016 Apr;51(4):370-9. doi: 10.1007/s00535-015-1116-6. Epub 2015 Sep 3.
• [9] Perianal Crohn's Disease is Associated with Distal Colonic Disease, Stricturing Disease Behavior, IBD-Associated Serologies and Genetic Variation in the JAK-STAT Pathway.Inflamm Bowel Dis. 2016 Apr;22(4):862-9. doi: 10.1097/MIB.0000000000000705.
• [10] YWHAE Rearrangement in a Purely Conventional Low-grade Endometrial Stromal Sarcoma that Transformed Over Time to High-grade Sarcoma: Importance of Molecular Testing.Int J Gynecol Pathol. 2018 Sep;37(5):441-447. doi: 10.1097/PGP.0000000000000451.
• [11] Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.Nat Genet. 2013 Nov;45(11):1353-60. doi: 10.1038/ng.2770. Epub 2013 Sep 29.
• [12] Next-generation Sequencing of an Ovarian Spindle Cell Tumor Identified an Ovarian Low-grade Endometrial Stromal Sarcoma: A Rare Entity.Int J Gynecol Pathol. 2019 Sep;38(5):474-478. doi: 10.1097/PGP.0000000000000540.
• [13] Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.Gynecol Oncol. 2019 May;153(2):343-355. doi: 10.1016/j.ygyno.2019.02.023. Epub 2019 Mar 19.
• [14] Identification of PTPN22, ST6GAL1 and JAZF1 as psoriasis risk genes demonstrates shared pathogenesis between psoriasis and diabetes.Exp Dermatol. 2017 Nov;26(11):1112-1117. doi: 10.1111/exd.13393. Epub 2017 Aug 25.
• [15] Genetics of rheumatoid arthritis contributes to biology and drug discovery.Nature. 2014 Feb 20;506(7488):376-81. doi: 10.1038/nature12873. Epub 2013 Dec 25.
• [16] Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.Nat Genet. 2018 Aug;50(8):1072-1080. doi: 10.1038/s41588-018-0157-1. Epub 2018 Jul 16.
• [17] Over-expression of JAZF1 promotes cardiac microvascular endothelial cell proliferation and angiogenesis via activation of the Akt signaling pathway in rats with myocardial ischemia-reperfusion.Cell Cycle. 2019 Jul;18(14):1619-1634. doi: 10.1080/15384101.2019.1629774. Epub 2019 Jun 18.
• [18] Novel Susceptibility Loci for Moyamoya Disease Revealed by a Genome-Wide Association Study.Stroke. 2018 Jan;49(1):11-18. doi: 10.1161/STROKEAHA.117.017430.
• [19] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [20] Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.Am J Hum Genet. 2019 Apr 4;104(4):665-684. doi: 10.1016/j.ajhg.2019.02.022. Epub 2019 Mar 28.
• [21] Identification of a novel, recurrent MBTD1-CXorf67 fusion in low-grade endometrial stromal sarcoma.Int J Cancer. 2014 Mar 1;134(5):1112-22. doi: 10.1002/ijc.28440. Epub 2013 Sep 4.
• [22] Genetic variants at the 16p13 locus confer risk for eosinophilic esophagitis.Genes Immun. 2019 Apr;20(4):281-292. doi: 10.1038/s41435-018-0034-z. Epub 2018 Jun 8.
• [23] MicroRNA-1275 inhibits cell migration and invasion in gastric cancer by regulating vimentin and E-cadherin via JAZF1.BMC Cancer. 2019 Jul 29;19(1):740. doi: 10.1186/s12885-019-5929-1.
• [24] Gout and type 2 diabetes have a mutual inter-dependent effect on genetic risk factors and higher incidences.Rheumatology (Oxford). 2012 Apr;51(4):715-20. doi: 10.1093/rheumatology/ker373. Epub 2011 Dec 16.
• [25] Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.Nat Genet. 2012 Oct;44(10):1090-7. doi: 10.1038/ng.2411. Epub 2012 Sep 9.
• [26] 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.
• [27] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [28] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [29] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [32] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [33] 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.
• [34] 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.
• [35] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
• [36] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.