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POU6F2 (POU domain, class 6, transcription factor 2)

Identity

Other namesRPF-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

Nomenclature
HGNC (Hugo)POU6F2   21694
Cards
AtlasPOU6F2ID42963ch7p14
Entrez_Gene (NCBI)POU6F2  11281  POU class 6 homeobox 2
GeneCards (Weizmann)POU6F2
Ensembl (Hinxton)ENSG00000106536 [Gene_View]  chr7:39017609-39504390 [Contig_View]  POU6F2 [Vega]
ICGC DataPortalENSG00000106536
cBioPortalPOU6F2
AceView (NCBI)POU6F2
Genatlas (Paris)POU6F2
WikiGenes11281
SOURCE (Princeton)NM_001166018 NM_007252
Genomic and cartography
GoldenPath (UCSC)POU6F2  -  7p14.1   chr7:39017609-39504390 +  7p14.1   [Description]    (hg19-Feb_2009)
EnsemblPOU6F2 - 7p14.1 [CytoView]
Mapping of homologs : NCBIPOU6F2 [Mapview]
OMIM601583   609062   
Gene and transcription
Genbank (Entrez)AK309700 BC152915 DN991890 U91935
RefSeq transcript (Entrez)NM_001166018 NM_007252
RefSeq genomic (Entrez)AC_000139 NC_000007 NC_018918 NG_016022 NT_007819 NW_001839003 NW_001839004 NW_004929329
Consensus coding sequences : CCDS (NCBI)POU6F2
Cluster EST : UnigeneHs.137106 [ NCBI ]
CGAP (NCI)Hs.137106
Alternative Splicing : Fast-db (Paris)GSHG0027299
Alternative Splicing GalleryENSG00000106536
Gene ExpressionPOU6F2 [ NCBI-GEO ]     POU6F2 [ SEEK ]   POU6F2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP78424 (Uniprot)
NextProtP78424  [Medical]
With graphics : InterProP78424
Splice isoforms : SwissVarP78424 (Swissvar)
Domaine pattern : Prosite (Expaxy)HOMEOBOX_2 (PS50071)    POU_1 (PS00035)    POU_2 (PS00465)    POU_3 (PS51179)   
Domains : Interpro (EBI)Homeobox_dom [organisation]   Homeodomain-like [organisation]   Lambda_DNA-bd_dom [organisation]   POU [organisation]   POU_specific [organisation]  
Related proteins : CluSTrP78424
Domain families : Pfam (Sanger)Homeobox (PF00046)    Pou (PF00157)   
Domain families : Pfam (NCBI)pfam00046    pfam00157   
Domain families : Smart (EMBL)HOX (SM00389)  POU (SM00352)  
DMDM Disease mutations11281
Blocks (Seattle)P78424
Human Protein AtlasENSG00000106536 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP78424
HPRD10162
IPIIPI00926929   IPI00220088   IPI00978343   IPI00925686   
Protein Interaction databases
DIP (DOE-UCLA)P78424
IntAct (EBI)P78424
FunCoupENSG00000106536
BioGRIDPOU6F2
InParanoidP78424
Interologous Interaction database P78424
IntegromeDBPOU6F2
STRING (EMBL)POU6F2
Ontologies - Pathways
Ontology : AmiGOsequence-specific DNA binding transcription factor activity  nucleus  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  ganglion mother cell fate determination  central nervous system development  visual perception  sequence-specific DNA binding  
Ontology : EGO-EBIsequence-specific DNA binding transcription factor activity  nucleus  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  ganglion mother cell fate determination  central nervous system development  visual perception  sequence-specific DNA binding  
Protein Interaction DatabasePOU6F2
Wikipedia pathwaysPOU6F2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)POU6F2
snp3D : Map Gene to Disease11281
SNP (GeneSNP Utah)POU6F2
SNP : HGBasePOU6F2
Genetic variants : HAPMAPPOU6F2
Exome VariantPOU6F2
1000_GenomesPOU6F2 
ICGC programENSG00000106536 
Somatic Mutations in Cancer : COSMICPOU6F2 
CONAN: Copy Number AnalysisPOU6F2 
Mutations and Diseases : HGMDPOU6F2
Mutations and Diseases : intOGenPOU6F2
Genomic VariantsPOU6F2  POU6F2 [DGVbeta]
dbVarPOU6F2
ClinVarPOU6F2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM601583    609062   
MedgenPOU6F2
GENETestsPOU6F2
Disease Genetic AssociationPOU6F2
Huge Navigator POU6F2 [HugePedia]  POU6F2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGenePOU6F2
Homology/Alignments : Family Browser (UCSC)POU6F2
Phylogenetic Trees/Animal Genes : TreeFamPOU6F2
Chemical/Protein Interactions : CTD11281
Chemical/Pharm GKB GenePA134969420
Clinical trialPOU6F2
Cancer Resource (Charite)ENSG00000106536
Other databases
Probes
Litterature
PubMed12 Pubmed reference(s) in Entrez
CoreMinePOU6F2
iHOPPOU6F2
OncoSearchPOU6F2

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 articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written06-2005Daniela 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. 2005;9(4):280-281.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/POU6F2ID42963ch7p14.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Oct 4 12:52:03 CEST 2014

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