WRAP53 (WD repeat containing, antisense to TP53)
2010-11-01 Marianne Farnebo AffiliationKarolinska Institutet, Cancer Center Karolinska (CCK) R8 :04, 17176 Stockholm, Sweden
Identity
HGNC
LOCATION
17p13.1
LOCUSID
ALIAS
DKCB3,TCAB1,WDR79
FUSION GENES
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
Expression: widely expressed at low levels.
Localisation: cytoplasm and nucleus.
Function: regulates p53 mRNA levels by interacting with the 5UTR of p53 mRNA.
Homology: conserved in mouse.
Diseases implication currently not analysed.
Pseudogene
Not known.
Proteins
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
Entity name
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 name
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17683073 | 2007 | Common genetic variation in TP53 and its flanking genes, WDR79 and ATP1B2, and susceptibility to breast cancer. | Garcia-Closas M et al |
| 19276375 | 2009 | Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer. | Schildkraut JM et al |
| 19285445 | 2009 | A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles. | Tycowski KT et al |
| 19179534 | 2009 | A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. | Venteicher AS et al |
Other Information
Locus ID:
NCBI: 55135
MIM: 612661
HGNC: 25522
Ensembl: ENSG00000141499
Variants:
dbSNP: 55135
ClinVar: 55135
TCGA: ENSG00000141499
COSMIC: WRAP53
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36706151 | 2023 | Differential effects of WRAP53 transcript variants on non-small cell lung cancer cell behaviors. | 2 |
| 37267110 | 2023 | TCAB1 prevents nucleolar accumulation of the telomerase RNA to facilitate telomerase assembly. | 8 |
| 36706151 | 2023 | Differential effects of WRAP53 transcript variants on non-small cell lung cancer cell behaviors. | 2 |
| 37267110 | 2023 | TCAB1 prevents nucleolar accumulation of the telomerase RNA to facilitate telomerase assembly. | 8 |
| 35642155 | 2022 | [Effect of WRAP53 β Targeted Co-Inhibitory Pathways Based on Comprehensive Bioinformatics Analysis in Treating Squamous Cell Carcinoma of the Head and Neck]. | 0 |
| 36116037 | 2022 | Next-generation sequencing errors due to genetic variation in WRAP53 encoding TCAB1 on chromosome 17. | 0 |
| 35642155 | 2022 | [Effect of WRAP53 β Targeted Co-Inhibitory Pathways Based on Comprehensive Bioinformatics Analysis in Treating Squamous Cell Carcinoma of the Head and Neck]. | 0 |
| 36116037 | 2022 | Next-generation sequencing errors due to genetic variation in WRAP53 encoding TCAB1 on chromosome 17. | 0 |
| 32303682 | 2020 | Biallelic mutations in WRAP53 result in dysfunctional telomeres, Cajal bodies and DNA repair, thereby causing Hoyeraal-Hreidarsson syndrome. | 14 |
| 33028529 | 2020 | Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke. | 9 |
| 32303682 | 2020 | Biallelic mutations in WRAP53 result in dysfunctional telomeres, Cajal bodies and DNA repair, thereby causing Hoyeraal-Hreidarsson syndrome. | 14 |
| 33028529 | 2020 | Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke. | 9 |
| 30759234 | 2019 | TDP-43 regulates site-specific 2'-O-methylation of U1 and U2 snRNAs via controlling the Cajal body localization of a subset of C/D scaRNAs. | 18 |
| 31387111 | 2019 | Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer. | 9 |
| 30759234 | 2019 | TDP-43 regulates site-specific 2'-O-methylation of U1 and U2 snRNAs via controlling the Cajal body localization of a subset of C/D scaRNAs. | 18 |
Citation
Marianne Farnebo
WRAP53 (WD repeat containing, antisense to TP53)
Atlas Genet Cytogenet Oncol Haematol. 2010-11-01
Online version: http://atlasgeneticsoncology.org/gene/50705
