Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGSP4XJ)

• DOT Name: POU domain, class 6, transcription factor 1 (POU6F1)
• Synonyms: Brain-specific homeobox/POU domain protein 5; Brain-5; Brn-5; mPOU homeobox protein
• Gene Name: POU6F1
• Related Disease:
  Advanced cancer
  Bipolar depression
  Clear cell adenocarcinoma
  Disease of orbital part of eye adnexa
  Histiocytosis
• UniProt ID: PO6F1_HUMAN
• PDB ID: 3D1N
• Pfam ID: PF00046 ; PF00157
• Sequence:
  MPGISSQILTNAQGQVIGTLPWVVNSASVAAPAPAQSLQVQAVTPQLLLNAQGQVIATLA
  SSPLPPPVAVRKPSTPESPAKSEVQPIQPTPTVPQPAVVIASPAPAAKPSASAPIPITCS
  ETPTVSQLVSKPHTPSLDEDGINLEEIREFAKNFKIRRLSLGLTQTQVGQALTATEGPAY
  SQSAICRFEKLDITPKSAQKLKPVLEKWLNEAELRNQEGQQNLMEFVGGEPSKKRKRRTS
  FTPQAIEALNAYFEKNPLPTGQEITEIAKELNYDREVVRVWFCNRRQTLKNTSKLNVFQI
  P
• Function: Transcription factor that binds preferentially to a variant of the octamer motif (5'-ATGATAAT-3').
• Tissue Specificity: In the embryo, expressed exclusively in the developing brain, whereas in the adult its expression is restricted to brain, heart, skeletal muscle and lung. In the brain, the highest expression levels are found in specific cell layers of the cortex, the olfactory bulb, the hippocampus and the cerebellum.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Bipolar depression	DISA75FU	Strong	Biomarker	[2]
Clear cell adenocarcinoma	DISYUGHZ	Strong	Altered Expression	[1]
Disease of orbital part of eye adnexa	DISGWPWX	Strong	Biomarker	[3]
Histiocytosis	DISIYLND	Strong	Biomarker	[3]

5 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 POU domain, class 6, transcription factor 1 (POU6F1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of POU domain, class 6, transcription factor 1 (POU6F1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of POU domain, class 6, transcription factor 1 (POU6F1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of POU domain, class 6, transcription factor 1 (POU6F1).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of POU domain, class 6, transcription factor 1 (POU6F1).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of POU domain, class 6, transcription factor 1 (POU6F1).	[9]

References

• [1] POU6F1 is the transcription factor that might be involved in cell proliferation of clear cell adenocarcinoma of the ovary.Hum Cell. 2009 Nov;22(4):94-100. doi: 10.1111/j.1749-0774.2009.00074.x.
• [2] Positron emission tomography quantification of serotonin-1A receptor binding in medication-free bipolar depression.Biol Psychiatry. 2009 Aug 1;66(3):223-30. doi: 10.1016/j.biopsych.2009.01.028. Epub 2009 Mar 17.
• [3] The histopathology of Erdheim-Chester disease: a comprehensive review of a molecularly characterized cohort.Mod Pathol. 2018 Apr;31(4):581-597. doi: 10.1038/modpathol.2017.160. Epub 2017 Dec 1.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [9] 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.