Atlas of Genetics and Cytogenetics in Oncology and Haematology
POU6F2 (POU domain, class 6, transcription factor 2)
| Identity |
| Other names | RPF-1 (Retina-derived POU-domain factor-1) |
| HGNC (Hugo) | POU6F2 |
| LocusID (NCBI) | 11281 |
| Location | 7p14.1 |
| Location_base_pair | Starts at 39017609 and ends at 39504390 bp from pter ( according to hg19-Feb_2009) [Mapping] |
| Local_order | Cen-CDC2L5-RALA-POU6F2-VPS41-AMPH-Tel |
| DNA/RNA |
| Note | POU6F2, previously named RPF-1 was isolated from a retina cDNA library |
 | |
| modified from http://genome.ucsc.edu/. Exons 1D to 10 of the gene are indicated by the vertical bars. | |
| Description | Thirteen exons, including 4 alternative exons 1, encompassing 458 Kb of genomic DNA (exons 1D to 10). |
| Transcription | Representative mRNA: U91935 2159 bases. Alternative splicings: four alternative exons 1; variable skipping of exon 6; variable skipping of both exons 8 and 9; +/- 36 aminoacids at the 5' end of exon 10. |
| Protein |
 | |
| modified from: http://www.ebi.ac.uk/ | |
| Description | POU6F2 is a member of a gene family whose products are characterized by the presence of a bipartite DNA-binding domain, consisting of a POU-specific domain and a POU heterodomain, separated by a variable polylinker. Both subdomains contain helix-turn-helix motifs that directly associate with the two components of bipartite DNA-binding sites. In addition, the POU6F2 protein contains a poly-glutamine (poly-Q) domain. Glutamine repeats are evolutionary conserved domains that may act as polar zippers by joining proteins bound to separate DNA segments and thus regulating their activity. POU domain family members are transcriptional regulators, many of which show highly restricted patterns of expression and are known to control cell type-specific differentiation pathways. POU6F2 encodes a deduced 648-amino acid protein. Alternative splicing potentially generates 24 distinct mRNA isoforms coding for proteins with different DNA-binding activity. The most abundant POU6F2 isoforms in human retina have an insertion of an evolutionarily conserved 36-amino acid peptide into the DNA recognition helix of the POU-specific domain. In vitro, the POU domain of POU6F2 lacking the insert binds to a consensus binding site for the product of another gene of the POU family, OCT1, whereas the alternatively spliced POU domain does not. |
| Expression | Immunohistochemical and ribonuclease protection assays showed that in adult mouse Pou6f2 is expressed within the central nervous system, where its expression is restricted to the medial habenula, to a dispersed population of neurons in the dorsal hypothalamus, and to subsets of ganglion and amacrine cells in the retina. In mouse embryo, Pou6f2 expression was detected during the earliest stages of retinal differentiation where it appears to be involved in the initial steps of amacrine and ganglion cell commitment. RT-PCR analysis of the mouse Pou6f2 gene revealed expression in kidney, adrenal gland, heart, stomach, muscle, and eye, but not in lung or skin, of mouse fetuses at embryonic day (E) 18, and in kidney, heart, muscle, spleen, and ovary, but not in lung, of adult mice. |
| Localisation | nuclear (presumptive). |
| Function | POU-domain family transcription factor (presumptive). |
| Homology | Other POU-domain family genes |
| Mutations |
| Note | The POU6F2 gene is located within an interval on chromosome 7p14 where loss of heterozygosity (LOH) was detected in a fraction of Wilms tumors (WTs), a kidney malignancy of childhood characterized by highly heterogeneous genetic alterations. By sequencing the POU6F2 gene in 12 WTs showing LOH on chromosome 7p14, 2 germline mutations of possible pathogenic significance were identified. The finding of the expression of the POU6F2 mouse homolog in both fetal and adult kidney, together with the demonstration of mutations in WT patients, suggest that the gene is a tumor suppressor and is involved in hereditary predisposition to WT. |
| Germinal | In a patient with WT and LOH at chromosome 7p14, a germline 552G-T transversion in exon 5 of the POU6F2 gene, resulting in a gln184-to-his (Q184H) substitution in a glutamine repeat domain, was identified. The patient showed loss of the constitutionally wildtype allele in tumor DNA. Neither the mother nor the father carried this mutation. Marker studies indicated that the deletion in tumor DNA was of maternal origin, suggesting that the identified base change most likely occurred as a de novo germline point mutation on the paternal chromosome. In a patient with WT showing LOH at chromosome 7p14, a germline C-to-G transversion in the untranslated portion of the alternatively spliced exon 1C of the POU6F2 gene was identified. The mutation was inherited from the unaffected mother. |
| Implicated in |
| Entity | Wilms tumor, or nephroblastoma |
| Prognosis | good with treatment according to National Wilms Tumor Study Group (NWTSG) or International Society of Paediatric Oncology (SIOP) or Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) |
| External links |
| Bibliography |
| Retina-derived POU-domain factor-1: a complex POU-domain gene implicated in the development of retinal ganglion and amacrine cells. |
| Zhou H, Yoshioka T, Nathans J |
| The Journal of neuroscience : the official journal of the Society for Neuroscience. 1996 ; 16 (7) : 2261-2274. |
| PMID 8601806 |
| The virtuoso of versatility: POU proteins that flex to fit. |
| Phillips K, Luisi B |
| Journal of molecular biology. 2000 ; 302 (5) : 1023-1039. |
| PMID 11183772 |
| Refinement within single yeast artificial chromosome clones of a minimal region commonly deleted on the short arm of chromosome 7 in Wilms tumours. |
| Perotti D, Testi MA, Mondini P, Pilotti S, Green ED, Pession A, Sozzi G, Pierotti MA, Fossati-Bellani F, Radice P |
| Genes, chromosomes & cancer. 2001 ; 31 (1) : 42-47. |
| PMID 11284034 |
| Germline mutations of the POU6F2 gene in Wilms tumors with loss of heterozygosity on chromosome 7p14. |
| Perotti D, De Vecchi G, Testi MA, Lualdi E, Modena P, Mondini P, Ravagnani F, Collini P, Di Renzo F, Spreafico F, Terenziani M, Sozzi G, Fossati-Bellani F, Radice P |
| Human mutation. 2004 ; 24 (5) : 400-407. |
| PMID 15459955 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 06-2005 | Daniela Perotti, Luisa Doneda, Paolo Radice |
| U.O.4 Genetic susceptibility to cancer, Istituto Nazionale Tumori, Via Venezian, 1, 20133 Milan, Italy |
| Citation |
| This paper should be referenced as such : |
| Perotti D, Doneda L, Radice P . POU6F2 (POU domain, class 6, transcription factor 2). Atlas Genet Cytogenet Oncol Haematol. June 2005 . URL : http://AtlasGeneticsOncology.org/Genes/POU6F2ID42963ch7p14.html |
This paper is referenced by INIST as such : |
| http://documents.irevues.inist.fr/bitstream/2042/38236/1/06-2005-POU6F2ID42963ch7p14.pdf [ Bibliographic record ] |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed May 1 13:01:13 CEST 2013 |
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