POU3F4

Summary

Gene Symbol: POU3F4
Description: POU class 3 homeobox 4
Alias: BRAIN-4, BRN-4, BRN4, DFN3, DFNX2, OCT-9, OTF-9, OTF9, POU domain, class 3, transcription factor 4, brain-specific homeobox/POU domain protein 4, octamer-binding transcription factor 9
Species: human
Products:     POU3F4

Top Publications

  1. Bitner Glindzicz M, Turnpenny P, Hoglund P, Kaariainen H, Sankila E, van der Maarel S, et al. Further mutations in Brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3. Hum Mol Genet. 1995;4:1467-9 pubmed
  2. Naranjo S, Voesenek K, de la Calle Mustienes E, Robert Moreno A, Kokotas H, Grigoriadou M, et al. Multiple enhancers located in a 1-Mb region upstream of POU3F4 promote expression during inner ear development and may be required for hearing. Hum Genet. 2010;128:411-9 pubmed publisher
    b>POU3F4 encodes a POU-domain transcription factor required for inner ear development. Defects in POU3F4 function are associated with X-linked deafness type 3 (DFN3)...
  3. Lee H, Song M, Kang M, Lee J, Kong K, Choi S, et al. Clinical and molecular characterizations of novel POU3F4 mutations reveal that DFN3 is due to null function of POU3F4 protein. Physiol Genomics. 2009;39:195-201 pubmed publisher
    ..deafness type 3 (DFN3), the most prevalent X-linked form of hereditary deafness, is caused by mutations in the POU3F4 locus, which encodes a member of the POU family of transcription factors...
  4. Stankovic K, Hennessey A, Herrmann B, Mankarious L. Cochlear implantation in children with congenital X-linked deafness due to novel mutations in POU3F4 gene. Ann Otol Rhinol Laryngol. 2010;119:815-22 pubmed
    We report novel mutations in the POU3F4 gene resulting in congenital X-linked deafness DFN3, and describe the results of cochlear implantation in 4 boys (3 siblings) followed for an average of 3.5 years...
  5. Li J, Cheng J, Lu Y, Lu Y, Chen A, Sun Y, et al. Identification of a novel mutation in POU3F4 for prenatal diagnosis in a Chinese family with X-linked nonsyndromic hearing loss. J Genet Genomics. 2010;37:787-93 pubmed publisher
    ..A missense mutation (c.647G?A) in the POU3F4 gene caused a substitution from glycine to glutamic acid at position 216 (p...
  6. de Kok Y, Cremers C, Ropers H, Cremers F. The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation. Hum Mutat. 1997;10:207-11 pubmed
    We have investigated two unrelated males with X-linked deafness type 3 (DFN3) for mutations in the POU3F4 gene. In one patient, we observed a mutation that is predicted to result in an Arg330Ser amino acid substitution...
  7. Marlin S, Moizard M, David A, Chaissang N, Raynaud M, Jonard L, et al. Phenotype and genotype in females with POU3F4 mutations. Clin Genet. 2009;76:558-63 pubmed publisher
    ..To date, four loci for DFN have been identified and only one gene, POU3F4 responsible for DFN3, has been cloned...
  8. de Kok Y, van der Maarel S, Bitner Glindzicz M, Huber I, Monaco A, Malcolm S, et al. Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4. Science. 1995;267:685-8 pubmed
    ..Here, it is reported that a candidate gene for this disorder, Brain 4 (POU3F4), which encodes a transcription factor with a POU domain, maps to the same interval...
  9. Phippard D, Heydemann A, Lechner M, Lu L, Lee D, Kyin T, et al. Changes in the subcellular localization of the Brn4 gene product precede mesenchymal remodeling of the otic capsule. Hear Res. 1998;120:77-85 pubmed
    ..formation of the temporal bone, we have characterized the developmental expression pattern of the mouse gene, Brn4/Pou3f4, which plays a central role in bony labyrinth formation...

More Information

Publications59

  1. Velychko S, Kang K, Kim S, Kwak T, Kim K, Park C, et al. Fusion of Reprogramming Factors Alters the Trajectory of Somatic Lineage Conversion. Cell Rep. 2019;27:30-39.e4 pubmed publisher
    ..Replacing Oct4 with the neuro-specific factor Brn4 leads to transdifferentiation of fibroblasts into induced neural stem cells (iNSCs)...
  2. Aristidou C, Theodosiou A, Bak M, Mehrjouy M, Constantinou E, Alexandrou A, et al. Position effect, cryptic complexity, and direct gene disruption as disease mechanisms in de novo apparently balanced translocation cases. PLoS ONE. 2018;13:e0205298 pubmed publisher
    ..pattern was observed and the der(X) breakpoint mapped ~87kb upstream an X-linked deafness gene namely POU3F4, thus suggesting an underlying long-range position effect mechanism...
  3. Han J, Nguyen P, Oh D, Han J, Kim A, Kim M, et al. Elucidation of the unique mutation spectrum of severe hearing loss in a Vietnamese pediatric population. Sci Rep. 2019;9:1604 pubmed publisher
    ..2%), followed by GJB2 (6.9%), MYO7A (5.5%), SLC26A4 (4.6%), TMC1 (1.8%), ESPN (1.8%), POU3F4 (1.8%), MYH14 (1.8%), EYA1 (1.8%), and MR-RNR1 (1.1%)...
  4. Gong W, Gong R, Zhao B. HRCT and MRI findings in X-linked non-syndromic deafness patients with a POU3F4 mutation. Int J Pediatr Otorhinolaryngol. 2014;78:1756-62 pubmed publisher
    The aim of this study was to analyze HRCT and MRI findings in patients with X-linked non-syndromic deafness and a POU3f4 mutation...
  5. Li F, Su Y, Cheng Y, Jiang X, Peng Y, Li Y, et al. Conditional deletion of Men1 in the pancreatic β-cell leads to glucagon-expressing tumor development. Endocrinology. 2015;156:48-57 pubmed publisher
    ..and expressed the mature α-cell-specific transcription factors Brain-specific homeobox POU domain protein 4 (Brn4) and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (MafB)...
  6. Coate T, Raft S, Zhao X, Ryan A, Crenshaw E, Kelley M. Otic mesenchyme cells regulate spiral ganglion axon fasciculation through a Pou3f4/EphA4 signaling pathway. Neuron. 2012;73:49-63 pubmed publisher
    ..Here, we show that radial bundle fasciculation and synapse formation are disrupted when Pou3f4 (DFNX2) is deleted from otic mesenchyme...
  7. Su Y, Gao X, Huang S, Mao J, Huang B, Zhao J, et al. Clinical and molecular characterization of POU3F4 mutations in multiple DFNX2 Chinese families. BMC Med Genet. 2018;19:157 pubmed publisher
    ..hearing loss (HL) cases are caused by various mutations in the POU domain class 3 transcription factor 4 (POU3F4) gene...
  8. Cabanillas R, Diñeiro M, Cifuentes G, Castillo D, Pruneda P, Alvarez R, et al. Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients. BMC Med Genomics. 2018;11:58 pubmed publisher
    ..3% (3/21) X-linked (COL4A5 [de novo], POU3F4, PRPS1). 46.9% of causative variants (15/32) were not in the databases. 28...
  9. Raft S, Coate T, Kelley M, Crenshaw E, Wu D. Pou3f4-mediated regulation of ephrin-b2 controls temporal bone development in the mouse. PLoS ONE. 2014;9:e109043 pubmed publisher
    The temporal bone encases conductive and sensorineural elements of the ear. Mutations of POU3F4 are associated with unique temporal bone abnormalities and X-linked mixed deafness (DFNX2/DFN3)...
  10. Kidokoro Y, Karasawa K, Minowa O, Sugitani Y, Noda T, Ikeda K, et al. Deficiency of transcription factor Brn4 disrupts cochlear gap junction plaques in a model of DFN3 non-syndromic deafness. PLoS ONE. 2014;9:e108216 pubmed publisher
    b>Brn4, which encodes a POU transcription factor, is the gene responsible for DFN3, an X chromosome-linked, non-syndromic type of hearing loss...
  11. Ishii J, Sato H, Yazawa T, Shishido Hara Y, Hiramatsu C, Nakatani Y, et al. Class III/IV POU transcription factors expressed in small cell lung cancer cells are involved in proneural/neuroendocrine differentiation. Pathol Int. 2014;64:415-22 pubmed publisher
    ..Because class III POU genes (POU3F1, POU3F2, POU3F3, and POU3F4) and class IV POU genes (POU4F1, POU4F2, and POU4F3) share similar properties in neural development, we analyzed ..
  12. Kim L, Wisely C, Lucius S, Weingarten J, Dodson E. Positive Outcomes and Surgical Strategies for Bilateral Cochlear Implantation in a Child With X-Linked Deafness. Ann Otol Rhinol Laryngol. 2016;125:173-6 pubmed publisher
    ..with bilateral profound sensorineural hearing loss and was confirmed to have X-linked deafness secondary to POU3F4 gene mutation...
  13. Chang Y, Srivastava Y, Hu C, Joyce A, Yang X, Zuo Z, et al. Quantitative profiling of selective Sox/POU pairing on hundreds of sequences in parallel by Coop-seq. Nucleic Acids Res. 2017;45:832-845 pubmed publisher
    ..By contrast, Oct4 and the three neural class III POU factors Brn2, Brn4 and Oct6 assemble with Sox2 in a surprisingly indistinguishable manner...
  14. Malik V, Zimmer D, Jauch R. Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming. Cell Mol Life Sci. 2018;75:1587-1612 pubmed publisher
    ..Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only essential regulators of development but have also been successfully employed to reprogram somatic ..
  15. Giordano M, Gertosio C, Pagani S, Meazza C, Fusco I, Bozzola E, et al. 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;16:74 pubmed publisher
    ..intellectual disability), TBX22 (a gene whose alterations have been related to the presence of cleft palate), POU3F4 (mutated in X-linked deafness) and ITM2A (a gene involved in cartilage development)...
  16. Moteki H, Shearer A, Izumi S, Kubota Y, Azaiez H, Booth K, et al. De novo mutation in X-linked hearing loss-associated POU3F4 in a sporadic case of congenital hearing loss. Ann Otol Rhinol Laryngol. 2015;124 Suppl 1:169S-76S pubmed publisher
    ..a male patient with no family history of hearing loss, in whom we identified a novel de novo mutation in the POU3F4 gene...
  17. Yu Q, Chen J, Deng W, Cao X, Wang Y, Zhou J, et al. Direct reprogramming of mouse fibroblasts into neural cells via Porphyra yezoensis polysaccharide based high efficient gene co-delivery. J Nanobiotechnology. 2017;15:82 pubmed publisher
    ..yezoensis polysaccharide (Ed-PYP) served as a gene carrier and a group of plasmids that encode Ascl1, Brn4, and Tcf3 (pABT) self-assembled into nanoparticles...
  18. Barashkov N, Klarov L, Teryutin F, Solovyev A, Pshennikova V, Konnikova E, et al. 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;104:94-97 pubmed publisher
    Here, we report a novel hemizygous transition c.975G>A (p.Trp325*) in POU3F4 gene (Xq21) found in two deaf half-brothers from one Yakut family (Eastern Siberia, Russia) with identical inner ear abnormalities ("corkscrew" cochlea with ..
  19. Wu C, Lin Y, Liu T, Lin K, Yang W, Hsu C, et al. Identifying Children With Poor Cochlear Implantation Outcomes Using Massively Parallel Sequencing. Medicine (Baltimore). 2015;94:e1073 pubmed publisher
    ..G292R variant. Mutations in the WFS1, GJB3, ESRRB, LRTOMT, MYO3A, and POU3F4 genes were detected in 7 (23%) of the 30 matched controls...
  20. Kim S, Kim J, Kwak T, Park S, Kim K, Park H, et al. Generation of Integration-free Induced Neural Stem Cells from Mouse Fibroblasts. J Biol Chem. 2016;291:14199-212 pubmed publisher
    The viral vector-mediated overexpression of the defined transcription factors, Brn4/Pou3f4, Sox2, Klf4, and c-Myc (BSKM), could induce the direct conversion of somatic fibroblasts into induced neural stem cells (iNSCs)...
  21. Wester J, Merna C, Peng K, Lewis R, Sepahdari A, Ishiyama G, et al. Facial nerve stimulation following cochlear implantation for X-linked stapes gusher syndrome leading to identification of a novel POU3F4 mutation. Int J Pediatr Otorhinolaryngol. 2016;91:121-123 pubmed publisher
    ..769C > T nucleotide change in the POU domain, class 3, transcription factor 4 gene (POU3F4). Inactivation of electrodes 1 and 19-21 successfully abated facial nerve stimulation.
  22. Lu P, Chen X, Feng Y, Zeng Q, Jiang C, Zhu X, et al. Integrated transcriptome analysis of human iPS cells derived from a fragile X syndrome patient during neuronal differentiation. Sci China Life Sci. 2016;59:1093-1105 pubmed
    ..from other platforms, we found up-regulation of many genes encoding TFs for neuronal differentiation (WNT1, BMP4, POU3F4, TFAP2C, and PAX3), down-regulation of potassium channels (KCNA1, KCNC3, KCNG2, KCNIP4, KCNJ3, KCNK9, and KCNT1) ..
  23. Xia A, Kikuchi T, Minowa O, Katori Y, Oshima T, Noda T, et al. Late-onset hearing loss in a mouse model of DFN3 non-syndromic deafness: morphologic and immunohistochemical analyses. Hear Res. 2002;166:150-8 pubmed
    Recently, we reported that homozygous males and females of a mouse model of DFN3 non-syndromic deafness generated by the deletion of Brn-4 transcription factor showed profound deafness due to severe alterations in the cochlear spiral ..
  24. Stanton S, Griffin A, Stockley T, Brown C, Young T, Benteau T, et al. X-linked hearing loss: two gene mutation examples provide generalizable implications for clinical care. Am J Audiol. 2014;23:190-200 pubmed publisher
    ..members interviewed to compare hearing thresholds and case histories between cases with mutations in SMPX versus POU3F4. The family pedigrees reveal characteristic X-linked inheritance patterns...
  25. Robert Moreno l, Naranjo S, de la Calle Mustienes E, G mez Skarmeta J, Alsina B. Characterization of new otic enhancers of the pou3f4 gene reveal distinct signaling pathway regulation and spatio-temporal patterns. PLoS ONE. 2010;5:e15907 pubmed publisher
    b>POU3F4 is a member of the POU-homedomain transcription factor family with a prominent role in inner ear development...
  26. Mizoshiri N, Kishida T, Yamamoto K, Shirai T, Terauchi R, Tsuchida S, et al. Transduction of Oct6 or Oct9 gene concomitant with Myc family gene induced osteoblast-like phenotypic conversion in normal human fibroblasts. Biochem Biophys Res Commun. 2015;467:1110-6 pubmed publisher
    ..The results may also lead to establishment of novel regenerative therapy for various bone resorption diseases. ..
  27. Kanno A, Mutai H, Namba K, Morita N, Nakano A, Ogahara N, et al. Frequency and specific characteristics of the incomplete partition type III anomaly in children. Laryngoscope. 2017;127:1663-1669 pubmed publisher
    ..the frequency of the incomplete partition type III anomaly and the genetic and clinical features associated with POU3F4 mutations in children with hearing loss...
  28. Pollak A, Lechowicz U, Kedra A, Stawinski P, Rydzanicz M, Furmanek M, et al. Novel and De Novo Mutations Extend Association of POU3F4 with Distinct Clinical and Radiological Phenotype of Hearing Loss. PLoS ONE. 2016;11:e0166618 pubmed publisher
    b>POU3F4 mutations (DFNX2) are the most prevalent among non-syndromic X-linked hearing loss (HL) identified to date...
  29. Malik K, Jaffe H, Brady J, Young W. The class III POU factor Brn-4 interacts with other class III POU factors and the heterogeneous nuclear ribonucleoprotein U. Brain Res Mol Brain Res. 1997;45:99-107 pubmed
    ..This result suggests another mechanism by which a POU protein can influence gene expression: by facilitating the processing of pre-mRNA whose transcription it has stimulated. ..
  30. Hagiwara H, Tamagawa Y, Kitamura K, Kodera K. A new mutation in the POU3F4 gene in a Japanese family with X-linked mixed deafness (DFN3). Laryngoscope. 1998;108:1544-7 pubmed
    ..mixed deafness showing a perilymphatic gusher at stapedectomy (DFN3) has been attributed to mutations in the POU3F4 gene. This study aimed to clarify an allelic variant of this gene...
  31. Choi B, An Y, Song J, Koo J, Lee J, Oh S, et al. Clinical observations and molecular variables of patients with hearing loss and incomplete partition type III. Laryngoscope. 2016;126:E123-8 pubmed publisher
    ..Mutations affecting POU3F4 were classified as extension (n = 2), truncation (n = 3), large genomic deletion (n = 2), or missense substitution ..
  32. Han M, Lu Y, Bian X, Wang L, Huang S, Wang G, et al. [Prenatal genetic test and clinical guidance for 213 hereditary deaf families]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2012;47:127-31 pubmed
    ..212 families were confirmed by means of the genetic test of GJB2, SLC26A4 and mtDNA 12sRNA, but one family carried POU3F4 c.647G > A heterozygous mutation causing X-linked hereditary hearing impairment confirmed by pedigree study...
  33. Song M, Lee K, Choi J, Bok J, Kim U. Nonsyndromic X-linked hearing loss. Front Biosci (Elite Ed). 2012;4:924-33 pubmed
    ..In addition to the POU3F4 gene, which was the first gene identified as causing nonsyndromic X-linked hearing loss, a second gene, PRPS1, has ..
  34. Douville P, Atanasoski S, Tobler A, Fontana A, Schwab M. The brain-specific POU-box gene Brn4 is a sex-linked transcription factor located on the human and mouse X chromosomes. Mamm Genome. 1994;5:180-2 pubmed
  35. Schild C, Prera E, Lüblinghoff N, Arndt S, Aschendorff A, Birkenhäger R. Novel mutation in the homeobox domain of transcription factor POU3F4 associated with profound sensorineural hearing loss. Otol Neurotol. 2011;32:690-4 pubmed publisher
    ..So far, 6 different X-linked loci have been mapped, but the causative gene POU3F4 has been identified only for the Locus DFN3...
  36. Wang Q, Han D, Yang W. [Detection of POU3F4 gene mutations in the Chinese pedigree with Y-linked hereditary hearing impairment]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2005;40:323-6 pubmed
    To analyze the mutations of candidate POU3F4 gene in the Chinese pedigree with Y linked hereditary hearing impairment...
  37. Du W, Han M, Wang D, Han B, Zong L, Lan L, et al. A POU3F4 Mutation Causes Nonsyndromic Hearing Loss in a Chinese X-linked Recessive Family. Chin Med J (Engl). 2017;130:88-92 pubmed publisher
    The molecular genetic research showed the association between X-linked hearing loss and mutations in POU3F4. This research aimed to identify a POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family...
  38. Shimazaki T, Arsenijevic Y, Ryan A, Rosenfeld M, Weiss S. A role for the POU-III transcription factor Brn-4 in the regulation of striatal neuron precursor differentiation. EMBO J. 1999;18:444-56 pubmed
    ..These findings suggest that Brn-4 mediates, at least in part, the actions of epigenetic signals that induce striatal neuron-precursor differentiation. ..
  39. Parzefall T, Shivatzki S, Lenz D, Rathkolb B, Ushakov K, Karfunkel D, et al. Cytoplasmic mislocalization of POU3F4 due to novel mutations leads to deafness in humans and mice. Hum Mutat. 2013;34:1102-10 pubmed publisher
    b>POU3F4 is a POU domain transcription factor that is required for hearing. In the ear, POU3F4 is essential for mesenchymal remodeling of the bony labyrinth and is the causative gene for DFNX2 human nonsyndromic deafness...
  40. Lin Y, Lin Y, Lu Y, Liu T, Chen C, Hsu C, et al. A novel missense variant in the nuclear localization signal of POU4F3 causes autosomal dominant non-syndromic hearing loss. Sci Rep. 2017;7:7551 pubmed publisher
    ..Lys328Glu compromised transportation of POU4F3 from the cytoplasm to the nucleus. POU3F4 p...
  41. Kandpal G, Jacob A, Kandpal R. Transcribed sequences encoded in the region involved in contiguous deletion syndrome that comprises X-linked stapes fixation and deafness. Somat Cell Mol Genet. 1996;22:511-7 pubmed
    ..In addition to identifying Brn4 (POU3f4), a POU domain containing transcription factor that is involved in DFN3 phenotype, we have isolated seven short ..
  42. Lee H, Lee S, Lee K, Lim E, Choi S, Park R, et al. Novel POU3F4 mutations and clinical features of DFN3 patients with cochlear implants. Clin Genet. 2009;75:572-5 pubmed publisher
  43. Choi J, Min B, Kim A, Koo J, Kim C, Park W, et al. De novo large genomic deletions involving POU3F4 in incomplete partition type III inner ear anomaly in East Asian populations and implications for genetic counseling. Otol Neurotol. 2015;36:184-90 pubmed publisher
    ..Two (20%) of the 10 DFNX2 carried a large genomic deletion affecting POU3F4, as proved by aCGH. PCR confirmed that the 2 deletions occurred de novo. Genetic alteration occurred de novo in 29...
  44. Yuan Y, Zhang X, Huang S, Zuo L, Zhang G, Song Y, et al. Common molecular etiologies are rare in nonsyndromic Tibetan Chinese patients with hearing impairment. PLoS ONE. 2012;7:e30720 pubmed publisher
    ..Five prominent deafness-related genes, GJB2, SLC26A4, GJB6, POU3F4, and mtDNA 12S rRNA, were analyzed. Inner ear development was evaluated by temporal CT...
  45. Bademci G, Lasisi A, Yariz K, Montenegro P, Menéndez I, Vinueza R, et al. Novel domain-specific POU3F4 mutations are associated with X-linked deafness: examples from different populations. BMC Med Genet. 2015;16:9 pubmed publisher
    Mutations in the POU3F4 gene cause X-linked deafness type 3 (DFN3), which is characterized by inner ear anomalies...
  46. Choi B, An Y, Park J, Jang J, Chung H, Kim A, et al. Audiological and surgical evidence for the presence of a third window effect for the conductive hearing loss in DFNX2 deafness irrespective of types of mutations. Eur Arch Otorhinolaryngol. 2013;270:3057-62 pubmed publisher
    ..study was to clarify the cause of the air-bone gap in incomplete partition (IP) type III cases according to the POU3F4 gene (DFNX2) mutation type...
  47. Choi B, Kim D, Chung T, Chang M, Kim E, Kim A, et al. Destabilization and mislocalization of POU3F4 by C-terminal frameshift truncation and extension mutation. Hum Mutat. 2013;34:309-16 pubmed publisher
    ..hearing loss is caused by various types of mutations of the POU domain class 3 transcription factor 4 gene (POU3F4). We found five unique missense and frameshift truncation and extension mutations in Korean patients...
  48. Engelkamp D, van Heyningen V. Transcription factors in disease. Curr Opin Genet Dev. 1996;6:334-42 pubmed
    ..Position effects with cytogenetic rearrangements well outside the coding region have been implicated for four of the genes discussed: POU3F4, SOX9, PAX6, and GL13.
  49. Song M, Lee H, Choi J, Kim S, Bok J, Kim U. Clinical evaluation of DFN3 patients with deletions in the POU3F4 locus and detection of carrier female using MLPA. Clin Genet. 2010;78:524-32 pubmed publisher
    ..deafness type 3 (DFN3), the most prevalent X-linked form of hereditary deafness, is caused by mutations of the POU3F4 locus in the Xq21 region...