Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0FKQ51)

• DOT Name: Putative POU domain, class 5, transcription factor 1B (POU5F1B)
• Synonyms: Oct4-pg1; Octamer-binding protein 3-like; Octamer-binding transcription factor 3-like
• Gene Name: POU5F1B
• Related Disease:
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal adenoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Gastric cancer
  Nasopharyngeal carcinoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Hepatocellular carcinoma
  Advanced cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland papillary carcinoma
  Thyroid tumor
• UniProt ID: P5F1B_HUMAN
• Pfam ID: PF00046 ; PF00157
• Sequence:
  MAGHLASDFAFSPPPGGGGDGPWGAEPGWVDPLTWLSFQGPPGGPGIGPGVGPGSEVWGI
  PPCPPPYELCGGMAYCGPQVGVGLVPQGGLETSQPESEAGVGVESNSNGASPEPCTVPPG
  AVKLEKEKLEQNPEKSQDIKALQKELEQFAKLLKQKRITLGYTQADVGLILGVLFGKVFS
  QKTICRFEALQLSFKNMCKLRPLLQKWVEEADNNENLQEICKAETLMQARKRKRTSIENR
  VRGNLENLFLQCPKPTLQISHIAQQLGLEKDVVRVWFCNRRQKGKRSSSDYAQREDFEAA
  GSPFSGGPVSFPPAPGPHFGTPGYGSPHFTALYSSVPFPEGEVFPPVSVITLGSPMHSN
• Function: Shows weak transcriptional activator activity.
• Tissue Specificity: Detected at the mRNA level in several cancer tissues (breast, uterine cervix, lung, thyroid gland, esophagus, colon, urinary bladder, and glioma), but absent in normal tissues.
• KEGG Pathway: Sig.ling pathways regulating pluripotency of stem cells (hsa04550)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[4]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[4]
Colon cancer	DISVC52G	Strong	Genetic Variation	[5]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[5]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[6]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[5]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[7]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[9]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[10]
Stomach cancer	DISKIJSX	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Disputed	Biomarker	[11]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]
Thyroid cancer	DIS3VLDH	Limited	Genetic Variation	[12]
Thyroid gland carcinoma	DISMNGZ0	Limited	Genetic Variation	[12]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Genetic Variation	[12]
Thyroid tumor	DISLVKMD	Limited	Genetic Variation	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Putative POU domain, class 5, transcription factor 1B (POU5F1B).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Putative POU domain, class 5, transcription factor 1B (POU5F1B).	[17]

5 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 Putative POU domain, class 5, transcription factor 1B (POU5F1B).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Putative POU domain, class 5, transcription factor 1B (POU5F1B).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Putative POU domain, class 5, transcription factor 1B (POU5F1B).	[16]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Putative POU domain, class 5, transcription factor 1B (POU5F1B).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Putative POU domain, class 5, transcription factor 1B (POU5F1B).	[15]

References

• [1] Low Expression of Pseudogene POU5F1B Affects Diagnosis and Prognosis in Acute Myeloid Leukemia (AML).Med Sci Monit. 2019 Jul 4;25:4952-4959. doi: 10.12659/MSM.914352.
• [2] Large-scale genotyping identifies 41 new loci associated with breast cancer risk.Nat Genet. 2013 Apr;45(4):353-61, 361e1-2. doi: 10.1038/ng.2563.
• [3] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [4] The Octamer-Binding Transcription Factor 4 (OCT4) Pseudogene, POU Domain Class 5 Transcription Factor 1B (POU5F1B), is Upregulated in Cervical Cancer and Down-Regulation Inhibits Cell Proliferation and Migration and Induces Apoptosis in Cervical Cancer Cell Lines.Med Sci Monit. 2019 Feb 14;25:1204-1213. doi: 10.12659/MSM.912109.
• [5] Novel Common Genetic Susceptibility Loci for Colorectal Cancer.J Natl Cancer Inst. 2019 Feb 1;111(2):146-157. doi: 10.1093/jnci/djy099.
• [6] Discovery of common and rare genetic risk variants for colorectal cancer.Nat Genet. 2019 Jan;51(1):76-87. doi: 10.1038/s41588-018-0286-6. Epub 2018 Dec 3.
• [7] The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer.Oncogene. 2015 Jan 8;34(2):199-208. doi: 10.1038/onc.2013.547. Epub 2013 Dec 23.
• [8] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.Nat Genet. 2010 Jul;42(7):599-603. doi: 10.1038/ng.601. Epub 2010 May 30.
• [9] Prospective study of DNA methylation at chromosome 8q24 in peripheral blood and prostate cancer risk.Br J Cancer. 2017 May 23;116(11):1470-1479. doi: 10.1038/bjc.2017.104. Epub 2017 May 2.
• [10] 12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population.Nat Commun. 2019 Sep 27;10(1):4422. doi: 10.1038/s41467-019-12267-6.
• [11] POU5F1B promotes hepatocellular carcinoma proliferation by activating AKT.Biomed Pharmacother. 2018 Apr;100:374-380. doi: 10.1016/j.biopha.2018.02.023. Epub 2018 Feb 16.
• [12] The common genetic variant rs944289 on chromosome 14q13.3 associates with risk of both malignant and benign thyroid tumors in the Japanese population.Thyroid. 2015 Mar;25(3):333-40. doi: 10.1089/thy.2014.0431. Epub 2015 Feb 5.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [17] 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.