Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNSW95F)

• DOT Name: POU domain, class 6, transcription factor 2 (POU6F2)
• Synonyms: Retina-derived POU domain factor 1; RPF-1
• Gene Name: POU6F2
• Related Disease:
  Advanced cancer
  Autism
  Childhood kidney Wilms tumor
  Motion sickness
  Neoplasm
  Wilms tumor
  Glaucoma/ocular hypertension
  Wilms tumor 5
• UniProt ID: PO6F2_HUMAN
• Pfam ID: PF00046 ; PF00157
• Sequence:
  MSALLQDPMIAGQVSKPLLSVRSEMNAELRGEDKAATSDSELNEPLLAPVESNDSEDTPS
  KLFGARGNPALSDPGTPDQHQASQTHPPFPVGPQPLLTAQQLASAVAGVMPGGPPALNQP
  ILIPFNMAGQLGGQQGLVLTLPTANLTNIQGLVAAAAAGGIMTLPLQNLQATSSLNSQLQ
  QLQLQLQQQQQQQQQQPPPSTNQHPQPAPQAPSQSQQQPLQPTPPQQPPPASQQPPAPTS
  QLQQAPQPQQHQPHSHSQNQNQPSPTQQSSSPPQKPSQSPGHGLPSPLTPPNPLQLVNNP
  LASQAAAAAAAMSSIASSQAFGNALSSLQGVTGQLVTNAQGQIIGTIPLMPNPGPSSQAA
  SGTQGLQVQPITPQLLTNAQGQIIATVIGNQILPVINTQGITLSPIKPGQQLHQPSQTSV
  GQAASQGNLLHLAHSQASMSQSPVRQASSSSSSSSSSSALSVGQLVSNPQTAAGEVDGVN
  LEEIREFAKAFKIRRLSLGLTQTQVGQALSATEGPAYSQSAICRHTILRSHFFLPQEAQE
  NTIASSLTAKLNPGLLYPARFEKLDITPKSAQKIKPVLERWMAEAEARHRAGMQNLTEFI
  GSEPSKKRKRRTSFTPQALEILNAHFEKNTHPSGQEMTEIAEKLNYDREVVRVWFCNKRQ
  ALKNTIKRLKQHEPATAVPLEPLTDSLEENS
• Function: Probable transcription factor likely to be involved in early steps in the differentiation of amacrine and ganglion cells. Recognizes and binds to the DNA sequence 5'-ATGCAAAT-3'. Isoform 1 does not bind DNA.
• Tissue Specificity: Expressed only within the CNS, where its expression is restricted to the medical habenulla, to a dispersed population of neurons in the dorsal hypothalamus, and to subsets of ganglion and amacrine cells in the retina.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Autism	DISV4V1Z	Strong	Biomarker	[2]
Childhood kidney Wilms tumor	DIS0NMK3	Strong	Biomarker	[3]
Motion sickness	DISZ2WZW	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Wilms tumor	DISB6T16	moderate	Biomarker	[3]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Genetic Variation	[5]
Wilms tumor 5	DISYW97P	Limited	Unknown	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of POU domain, class 6, transcription factor 2 (POU6F2).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of POU domain, class 6, transcription factor 2 (POU6F2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of POU domain, class 6, transcription factor 2 (POU6F2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of POU domain, class 6, transcription factor 2 (POU6F2).	[10]

References

• [1] Whole-Exome Sequencing of Salivary Gland Mucoepidermoid Carcinoma.Clin Cancer Res. 2017 Jan 1;23(1):283-288. doi: 10.1158/1078-0432.CCR-16-0720. Epub 2016 Jun 23.
• [2] A genome-wide scan for common alleles affecting risk for autism.Hum Mol Genet. 2010 Oct 15;19(20):4072-82. doi: 10.1093/hmg/ddq307. Epub 2010 Jul 27.
• [3] The murine Pou6f2 gene is temporally and spatially regulated during kidney embryogenesis and its human homolog is overexpressed in a subset of Wilms tumors.J Pediatr Hematol Oncol. 2006 Dec;28(12):791-7. doi: 10.1097/MPH.0b013e31802d3e65.
• [4] Genetic variants associated with motion sickness point to roles for inner ear development, neurological processes and glucose homeostasis.Hum Mol Genet. 2015 May 1;24(9):2700-8. doi: 10.1093/hmg/ddv028. Epub 2015 Jan 26.
• [5] Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma.PLoS Genet. 2018 Jan 25;14(1):e1007145. doi: 10.1371/journal.pgen.1007145. eCollection 2018 Jan.
• [6] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] 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.
• [9] 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.
• [10] 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.