Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKF5AF7)

• DOT Name: POU domain, class 3, transcription factor 4 (POU3F4)
• Synonyms: Brain-specific homeobox/POU domain protein 4; Brain-4; Brn-4; Octamer-binding protein 9; Oct-9; Octamer-binding transcription factor 9; OTF-9
• Gene Name: POU3F4
• Related Disease:
  Nonsyndromic genetic hearing loss
  X-linked intellectual disability
  Alzheimer disease
  Choroideremia
  Cleft palate
  Congenital hypothalamic hamartoma syndrome
  Deafness
  Ear malformation
  Intellectual disability, X-linked 1
  Isolated cleft palate
  Metastatic malignant neoplasm
  X-linked mixed hearing loss with perilymphatic gusher
  Hearing loss, X-linked 1
  Lung cancer
  Sensorineural hearing loss disorder
  Small-cell lung cancer
  Choroideremia-deafness-obesity syndrome
  Mitochondrial non-syndromic sensorineural hearing loss
  Rabies
  Intellectual disability
• UniProt ID: PO3F4_HUMAN
• Pfam ID: PF00046 ; PF00157
• Sequence:
  MATAASNPYSILSSTSLVHADSAGMQQGSPFRNPQKLLQSDYLQGVPSNGHPLGHHWVTS
  LSDGGPWSSTLATSPLDQQDVKPGREDLQLGAIIHHRSPHVAHHSPHTNHPNAWGASPAP
  NPSITSSGQPLNVYSQPGFTVSGMLEHGGLTPPPAAASAQSLHPVLREPPDHGELGSHHC
  QDHSDEETPTSDELEQFAKQFKQRRIKLGFTQADVGLALGTLYGNVFSQTTICRFEGLQL
  SFKNMCKLKPLLNKWLEEADSSTGSPTSIDKIAAQGRKRKKRTSIEVSVKGVLETHFLKC
  PKPAAQEISSLADSLQLEKEVVRVWFCNRRQKEKRMTPPGDQQPHEVYSHTVKTDTSCHD
  L
• Function: Probable transcription factor which exert its primary action widely during early neural development and in a very limited set of neurons in the mature brain.
• Tissue Specificity: Brain specific.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nonsyndromic genetic hearing loss	DISZX61P	Definitive	X-linked	[1]
X-linked intellectual disability	DISYJBY3	Definitive	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Choroideremia	DISH4N9B	Strong	Genetic Variation	[4]
Cleft palate	DIS6G5TF	Strong	Biomarker	[5]
Congenital hypothalamic hamartoma syndrome	DISO1UQ2	Strong	Biomarker	[6]
Deafness	DISKCLH4	Strong	Biomarker	[7]
Ear malformation	DISVJGPS	Strong	Genetic Variation	[8]
Intellectual disability, X-linked 1	DISET38E	Strong	Genetic Variation	[9]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[5]
Metastatic malignant neoplasm	DIS86UK6	Strong	Genetic Variation	[10]
X-linked mixed hearing loss with perilymphatic gusher	DISA86GW	Strong	X-linked	[11]
Hearing loss, X-linked 1	DISHL7OQ	moderate	Biomarker	[12]
Lung cancer	DISCM4YA	moderate	Biomarker	[13]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Genetic Variation	[14]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[13]
Choroideremia-deafness-obesity syndrome	DIS3HDJY	Supportive	X-linked	[15]
Mitochondrial non-syndromic sensorineural hearing loss	DISP6WS1	Supportive	Mitochondrial	[16]
Rabies	DISSC4V5	Disputed	Biomarker	[17]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Pantothenic acid	DM091H2	Approved	Pantothenic acid increases the expression of POU domain, class 3, transcription factor 4 (POU3F4).	[18]

1 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 increases the methylation of POU domain, class 3, transcription factor 4 (POU3F4).	[19]

References

• [1] 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.
• [2] Physical fine mapping of genes underlying X-linked deafness and non fra (X)-X-linked mental retardation at Xq21.Hum Genet. 1992 Aug;89(6):620-4. doi: 10.1007/BF00221950.
• [3] Therapeutic Effects of Transplantation of As-MiR-937-Expressing Mesenchymal Stem Cells in Murine Model of Alzheimer's Disease.Cell Physiol Biochem. 2015;37(1):321-30. doi: 10.1159/000430356. Epub 2015 Aug 24.
• [4] Choroideremia, sensorineural deafness, and primary ovarian failure in a woman with a balanced X-4 translocation.Ophthalmic Genet. 2000 Sep;21(3):185-9.
• [5] A 5.8 Mb interstitial deletion on chromosome Xq21.1 in a boy with intellectual disability, cleft palate, hearing impairment and combined growth hormone deficiency.BMC Med Genet. 2015 Sep 1;16:74. doi: 10.1186/s12881-015-0220-z.
• [6] Hypothalamic hamartomas and inner ear diverticula with X-linked stapes gusher syndrome - new associations?.Pediatr Radiol. 2020 Jan;50(1):142-145. doi: 10.1007/s00247-019-04497-z. Epub 2019 Aug 22.
• [7] Phenotype and genotype analysis of a Chinese family with prelingual X-linked hereditary hearing impairment.Chin Med J (Engl). 2009 Apr 5;122(7):830-3.
• [8] A novel pathogenic variant c.975G>A (p.Trp325*) in the POU3F4 gene in Yakut family (Eastern Siberia, Russia) with the X-linked deafness-2 (DFNX2).Int J Pediatr Otorhinolaryngol. 2018 Jan;104:94-97. doi: 10.1016/j.ijporl.2017.11.001. Epub 2017 Nov 6.
• [9] A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation.Genomics. 1999 Dec 15;62(3):332-43. doi: 10.1006/geno.1999.6004.
• [10] Expression of a restrictive receptor for interleukin 13 is associated with glial transformation.J Neurooncol. 2000 Jun;48(2):103-11. doi: 10.1023/a:1006446426611.
• [11] Genetic identification and molecular modeling characterization of a novel POU3F4 variant in two Italian deaf brothers. Int J Pediatr Otorhinolaryngol. 2020 Feb;129:109790. doi: 10.1016/j.ijporl.2019.109790. Epub 2019 Nov 22.
• [12] Nonsyndromic X-linked hearing loss.Front Biosci (Elite Ed). 2012 Jan 1;4(3):924-33. doi: 10.2741/E430.
• [13] Class III/IV POU transcription factors expressed in small cell lung cancer cells are involved in proneural/neuroendocrine differentiation.Pathol Int. 2014 Sep;64(9):415-22. doi: 10.1111/pin.12198.
• [14] Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients.BMC Med Genomics. 2018 Jul 9;11(1):58. doi: 10.1186/s12920-018-0375-5.
• [15] Molecular characterization of a novel X-linked syndrome involving developmental delay and deafness. Am J Med Genet A. 2007 Nov 1;143A(21):2564-75. doi: 10.1002/ajmg.a.31995.
• [16] Phenotype and genotype in females with POU3F4 mutations. Clin Genet. 2009 Dec;76(6):558-63. doi: 10.1111/j.1399-0004.2009.01215.x.
• [17] Comparative detection of rabies RNA by NASBA, real-time PCR and conventional PCR.J Virol Methods. 2011 Aug;175(2):278-82. doi: 10.1016/j.jviromet.2011.05.007. Epub 2011 May 11.
• [18] Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts. Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.
• [19] 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.