| Written | 2010-11 | Marianne Farnebo |
| Karolinska Institutet, Cancer Center Karolinska (CCK) R8 :04, 17176 Stockholm, Sweden |
| Identity |
| Alias_names | WDR79 |
| WD repeat domain 79 | |
| WD repeat containing, antisense to TP53 | |
| Alias_symbol (synonym) | FLJ10385 |
| TCAB1 | |
| Other alias | |
| HGNC (Hugo) | WRAP53 |
| LocusID (NCBI) | 55135 |
| Atlas_Id | 50705 |
| Location | 17p13.1 [Link to chromosome band 17p13] |
| Location_base_pair | Starts at 7688349 and ends at 7703502 bp from pter ( according to hg19-Feb_2009) [Mapping WRAP53.png] |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| NXN (17p13.3) / WRAP53 (17p13.1) | POLR2A (17p13.1) / WRAP53 (17p13.1) | TMEM107 (17p13.1) / WRAP53 (17p13.1) | |
| WRAP53 (17p13.1) / AHCY (20q11.22) |
| DNA/RNA |
| Description | The WRAP53 gene encompasses 16 kb of DNA; 13 exons (three non-coding alternative start exons: exon 1alpha, 1beta and 1gamma. Exon 1alpha directly overlaps the first exon of TP53 in an antisense fashion by up to 227 base pairs (bp), depending on transcription start site (TSS) usage. Exon 1gamma of WRAP53 is located in the first intron of TP53 overlapping the previously identified transcript Hp53int1 in an antisense fashion. |
| Transcription | At least 17 splice variants. 1.9 kb mRNA; 1647 bp open reading frame. Regulatory antisense RNA |
| Pseudogene | Not known. |
| Protein |
| Description | 548 amino acids; 75 kDa protein; contains from N-term to C-term, a proline-rich region (aa 8-57), a WD40 domain, 5 repeats (160-441), and a glycin-rich region (533-545). |
| Expression | Widely expressed, overexpressed in cancer. |
| Localisation | Cytoplasm and nucleus (enriched in Cajal bodies). |
| Function | Essential for Cajal body formation and maintenance. Targets the SMN complex, scaRNAs and telomerase enzyme (via TERC) to Cajal bodies. Inhibition of WRAP53 triggers mitochondrial-dependent apoptosis specifically in cancer cells. |
| Homology | Highly-conserved in mammals, the WD40 domain is conserved from human to fly. |
| Mutations |
| Note | Single nucleotide polymorphisms (SNPs) in women with breast cancer (see below). |
| Germinal | Not reported. |
| Somatic | Not reported. |
| Implicated in |
| Note | |
| Entity | Breast and ovarian cancer |
| Note | Single nucleotide polymorphisms (SNPs) in WRAP53 were found to be overrepresented in women with breast cancer, in particular estrogen receptor negative breast cancer. The same SNPs were also associated with aggressive ovarian cancer. The SNPs are located in the coding region of WRAP53 and results in the amino acid change R68G. |
| Entity | Spinal muscular atrophy (SMA) |
| Note | WRAP53 targets the SMN complex to Cajal Bodies. WRAP53 and SMN association is disrupted in SMA patients suggesting a role of WRAP53 in SMA pathogenesis. |
| Disease | Spinal muscular atrophy (SMA) is a common neurodegenerative disorder caused by reduced levels of SMN due to mutations or deletions of the SMN1 gene. SMA is the leading genetic cause of infant mortality worldwide, affecting approximately 1 in 6000 infants. |
| Bibliography |
| Common genetic variation in TP53 and its flanking genes, WDR79 and ATP1B2, and susceptibility to breast cancer. |
| Garcia-Closas M, Kristensen V, Langerod A, Qi Y, Yeager M, Burdett L, Welch R, Lissowska J, Peplonska B, Brinton L, Gerhard DS, Gram IT, Perou CM, Borresen-Dale AL, Chanock S. |
| Int J Cancer. 2007 Dec 1;121(11):2532-8. |
| PMID 17683073 |
| WRAP53 promotes cancer cell survival and is a potential target for cancer therapy. |
| Mahmoudi S, Henriksson S, Farnebo L, Roberg K, Farnebo M. |
| Cell Death Dis. 2011;2:e114;doi:10.1038/cddis.2010.90. |
| Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer. |
| Schildkraut JM, Goode EL, Clyde MA, Iversen ES, Moorman PG, Berchuck A, Marks JR, Lissowska J, Brinton L, Peplonska B, Cunningham JM, Vierkant RA, Rider DN, Chenevix-Trench G, Webb PM, Beesley J, Chen X, Phelan C, Sutphen R, Sellers TA, Pearce L, Wu AH, Van Den Berg D, Conti D, Elund CK, Anderson R, Goodman MT, Lurie G, Carney ME, Thompson PJ, Gayther SA, Ramus SJ, Jacobs I, Kruger Kjaer S, Hogdall E, Blaakaer J, Hogdall C, Easton DF, Song H, Pharoah PD, Whittemore AS, McGuire V, Quaye L, Anton-Culver H, Ziogas A, Terry KL, Cramer DW, Hankinson SE, Tworoger SS, Calingaert B, Chanock S, Sherman M, Garcia-Closas M; Australian Ovarian Cancer Study Group. |
| Cancer Res. 2009 Mar 15;69(6):2349-57. Epub 2009 Mar 10. |
| PMID 19276375 |
| A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles. |
| Tycowski KT, Shu MD, Kukoyi A, Steitz JA. |
| Mol Cell. 2009 Apr 10;34(1):47-57. Epub 2009 Mar 12. |
| PMID 19285445 |
| A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. |
| Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, Terns MP, Artandi SE. |
| Science. 2009 Jan 30;323(5914):644-8. |
| PMID 19179534 |
| Citation |
| This paper should be referenced as such : |
| Farnebo, M |
| WRAP53 (WD repeat containing, antisense to TP53) |
| Atlas Genet Cytogenet Oncol Haematol. 2011;15(7):596-597. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/WRAP53ID50705ch17p13.html |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ] |
|
NXN/WRAP53 (17p13)
POLR2A/WRAP53 (17p13) TMEM107/WRAP53 (17p13) t(17;20)(p13;q11) WRAP53/AHCY |
| Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Dyskeratosis congenita (DKC) |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Nov 13 22:10:40 CET 2019 |
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