WRN (Werner syndrome, RecQ helicase-like)
2001-03-01 Mounira Amor-Guéret AffiliationInstitut Curie - Section de Recherche, UMR 2027 CNRS, Bâtiment 110, Centre Universitaire, F-91405 Orsay Cedex, France
Identity
HGNC
LOCATION
8p12
LOCUSID
ALIAS
RECQ3,RECQL2,RECQL3
FUSION GENES
DNA/RNA
Transcription
4.4 kb mRNA
Proteins
Description
1432 amino acids; contains one ATP binding site, one DExH helicase box, one exonuclease domain unique among known RecQ helicases in the N-terminal region, a nuclear localization signal in the C-terminus and a direct repeat of 27 amino acids between the exonuclease and helicase domains.
Localisation
nuclear, predominant nucleolar localization.
Function
3-5 DNA helicase; 3-5 exonuclease; functionally interacts with DNA polymerase delta (POLD1) and RPA which are required for DNA replication and DNA repair, with Ku which is involved in double strand DNA break repair by non-homologous DNA end joining, and with p53.
Homology
Homologous to RecQ helicases, a subfamily of DExH box-containing DNA and RNA helicases. In particular, similarities with the four known human members in the RecQ subfamily, human RecQL, human BLM, the product of the Bloom syndrome gene, and the recently identified human RecQL4, involved in the Rothmund-Thomson syndrome, and RecQL5 proteins
Mutations
Germinal
WRN mutations are located over the entire gene and include stop codons, insertions/deletions and exon deletions: not a single missense mutation has been identified so far.
Implicated in
Entity name
Disease
Uncommon autosomal recessive disorder characterized by early onset of geriatric diseases, including atherosclerosis, osteoporosis, diabetes mellitus, juvenile cataract, graying of the hair and neoplasia, in particular soft-tissue sarcomas, in approximately 10% of WS patients.
Prognosis
WS patients die at mean age 46 +/- 11,6 years due to malignant tumors or cardiovascular infarctions.
Cytogenetics
Reciprocal chromosomal translocations and extensive genomic deletions.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 10506209 | 1999 | Physical and functional interaction between p53 and the Werner's syndrome protein. | Blander G et al |
| 11023999 | 2000 | The Werner syndrome protein contributes to induction of p53 by DNA damage. | Blander G et al |
| 10783163 | 2000 | Ku complex interacts with and stimulates the Werner protein. | Cooper MP et al |
| 8265666 | 1993 | The gene responsible for Werner syndrome may be a cell division "counting" gene. | Faragher RG et al |
| 2762303 | 1989 | Mutator phenotype of Werner syndrome is characterized by extensive deletions. | Fukuchi K et al |
| 2303247 | 1990 | Increased frequency of 6-thioguanine-resistant peripheral blood lymphocytes in Werner syndrome patients. | Fukuchi K et al |
| 1222585 | 1975 | Variegated translocation mosaicism in human skin fibroblast cultures. | Hoehn H et al |
| 10781066 | 2000 | Functional interaction between the Werner Syndrome protein and DNA polymerase delta. | Kamath-Loeb AS et al |
| 10880505 | 2000 | Functional interaction between Ku and the werner syndrome protein in DNA end processing. | Li B et al |
| 9618508 | 1998 | Nucleolar localization of the Werner syndrome protein in human cells. | Marciniak RA et al |
| 10220139 | 1999 | WRN mutations in Werner syndrome. | Moser MJ et al |
| 9402954 | 1997 | An apoptosis-inducing genotoxin differentiates heterozygotic carriers for Werner helicase mutations from wild-type and homozygous mutants. | Ogburn CE et al |
| 10982887 | 2000 | Telomere repeat DNA forms a large non-covalent complex with unique cohesive properties which is dissociated by Werner syndrome DNA helicase in the presence of replication protein A. | Ohsugi I et al |
| 8968742 | 1996 | Homozygous and compound heterozygous mutations at the Werner syndrome locus. | Oshima J et al |
| 11027336 | 2000 | Werner protein recruits DNA polymerase delta to the nucleolus. | Szekely AM et al |
| 8357345 | 1993 | Werner syndrome and biological ageing: a molecular genetic hypothesis. | Thweatt R et al |
| 10615119 | 2000 | Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts. | Wyllie FS et al |
| 9697700 | 1998 | Replication focus-forming activity 1 and the Werner syndrome gene product. | Yan H et al |
| 8602509 | 1996 | Positional cloning of the Werner's syndrome gene. | Yu CE et al |
Other Information
Locus ID:
NCBI: 7486
MIM: 604611
HGNC: 12791
Ensembl: ENSG00000165392
Variants:
dbSNP: 7486
ClinVar: 7486
TCGA: ENSG00000165392
COSMIC: WRN
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000165392 | ENST00000298139 | Q14191 |
| ENSG00000165392 | ENST00000650667 | A0A494C0M3 |
| ENSG00000165392 | ENST00000651642 | A0A494C0Y6 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38503516 | 2024 | WRN exonuclease imparts high fidelity on translesion synthesis by Y family DNA polymerases. | 0 |
| 38874681 | 2024 | RecQ helicase expression in patients with telomeropathies. | 0 |
| 38503516 | 2024 | WRN exonuclease imparts high fidelity on translesion synthesis by Y family DNA polymerases. | 0 |
| 38874681 | 2024 | RecQ helicase expression in patients with telomeropathies. | 0 |
| 36214313 | 2023 | A homozygous missense variant in the WRN gene segregating in a family with progressive pulmonary failure with recurrent spontaneous pneumothorax and interstitial lung disease. | 1 |
| 36583333 | 2023 | Werner syndrome protein works as a dimer for unwinding and replication fork regression. | 2 |
| 37932011 | 2023 | Comprehensive mapping of cell fates in microsatellite unstable cancer cells supports dual targeting of WRN and ATR. | 3 |
| 36214313 | 2023 | A homozygous missense variant in the WRN gene segregating in a family with progressive pulmonary failure with recurrent spontaneous pneumothorax and interstitial lung disease. | 1 |
| 36583333 | 2023 | Werner syndrome protein works as a dimer for unwinding and replication fork regression. | 2 |
| 37932011 | 2023 | Comprehensive mapping of cell fates in microsatellite unstable cancer cells supports dual targeting of WRN and ATR. | 3 |
| 35163467 | 2022 | R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1. | 7 |
| 35751457 | 2022 | WRN rescues replication forks compromised by a BRCA2 deficiency: Predictions for how inhibition of a helicase that suppresses premature aging tilts the balance to fork demise and chromosomal instability in cancer. | 3 |
| 35163467 | 2022 | R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1. | 7 |
| 35751457 | 2022 | WRN rescues replication forks compromised by a BRCA2 deficiency: Predictions for how inhibition of a helicase that suppresses premature aging tilts the balance to fork demise and chromosomal instability in cancer. | 3 |
| 33155383 | 2021 | Management guideline for Werner syndrome 2020. 4. Osteoporosis associated with Werner syndrome. | 3 |
Citation
Mounira Amor-Guéret
WRN (Werner syndrome, RecQ helicase-like)
Atlas Genet Cytogenet Oncol Haematol. 2001-03-01
Online version: http://atlasgeneticsoncology.org/gene/284/wrn
