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WRN (Werner syndrome, RecQ helicase-like)

Written2001-03Mounira Amor-Guéret
Institut Curie - Section de Recherche, UMR 2027 CNRS, Bâtiment 110, Centre Universitaire, F-91405 Orsay Cedex, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namesWerner syndrome
Werner syndrome RecQ like helicase
Alias_symbol (synonym)RECQL2
RECQ3
Other alias
HGNC (Hugo) WRN
LocusID (NCBI) 7486
Atlas_Id 284
Location 8p12  [Link to chromosome band 8p12]
Location_base_pair Starts at 31033262 and ends at 31175871 bp from pter ( according to hg19-Feb_2009)  [Mapping WRN.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)
CTDSPL (3p22.2) / WRN (8p12)PCMTD1 (8q11.23) / WRN (8p12)RREB1 (6p24.3) / WRN (8p12)
WRN (8p12) / ADAM9 (8p11.22)

DNA/RNA

Transcription 4.4 kb mRNA

Protein

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

Note
  
Entity Werner syndrome
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.
  

Bibliography

Physical and functional interaction between p53 and the Werner's syndrome protein.
Blander G, Kipnis J, Leal JF, Yu CE, Schellenberg GD, Oren M
The Journal of biological chemistry. 1999 ; 274 (41) : 29463-29469.
PMID 10506209
 
The Werner syndrome protein contributes to induction of p53 by DNA damage.
Blander G, Zalle N, Leal JF, Bar-Or RL, Yu CE, Oren M
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2000 ; 14 (14) : 2138-2140.
PMID 11023999
 
Ku complex interacts with and stimulates the Werner protein.
Cooper MP, Machwe A, Orren DK, Brosh RM, Ramsden D, Bohr VA
Genes & development. 2000 ; 14 (8) : 907-912.
PMID 10783163
 
The gene responsible for Werner syndrome may be a cell division counting gene.
Faragher RG, Kill IR, Hunter JA, Pope FM, Tannock C, Shall S
Proceedings of the National Academy of Sciences of the United States of America. 1993 ; 90 (24) : 12030-12034.
PMID 8265666
 
Mutator phenotype of Werner syndrome is characterized by extensive deletions.
Fukuchi K, Martin GM, Monnat RJ Jr
Proceedings of the National Academy of Sciences of the United States of America. 1989 ; 86 (15) : 5893-5897.
PMID 2762303
 
Increased frequency of 6-thioguanine-resistant peripheral blood lymphocytes in Werner syndrome patients.
Fukuchi K, Tanaka K, Kumahara Y, Marumo K, Pride MB, Martin GM, Monnat RJ Jr
Human genetics. 1990 ; 84 (3) : 249-252.
PMID 2303247
 
Variegated translocation mosaicism in human skin fibroblast cultures.
Hoehn H, Bryant EM, Au K, Norwood TH, Boman H, Martin GM
Cytogenetics and cell genetics. 1975 ; 15 (5) : 282-298.
PMID 1222585
 
Functional interaction between the Werner Syndrome protein and DNA polymerase delta.
Kamath-Loeb AS, Johansson E, Burgers PM, Loeb LA
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (9) : 4603-4608.
PMID 10781066
 
Functional interaction between Ku and the werner syndrome protein in DNA end processing.
Li B, Comai L
The Journal of biological chemistry. 2000 ; 275 (37) : 28349-28352.
PMID 10880505
 
Nucleolar localization of the Werner syndrome protein in human cells.
Marciniak RA, Lombard DB, Johnson FB, Guarente L
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (12) : 6887-6892.
PMID 9618508
 
WRN mutations in Werner syndrome.
Moser MJ, Oshima J, Monnat RJ Jr
Human mutation. 1999 ; 13 (4) : 271-279.
PMID 10220139
 
An apoptosis-inducing genotoxin differentiates heterozygotic carriers for Werner helicase mutations from wild-type and homozygous mutants.
Ogburn CE, Oshima J, Poot M, Chen R, Hunt KE, Gollahon KA, Rabinovitch PS, Martin GM
Human genetics. 1997 ; 101 (2) : 121-125.
PMID 9402954
 
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, Tokutake Y, Suzuki N, Ide T, Sugimoto M, Furuichi Y
Nucleic acids research. 2000 ; 28 (18) : 3642-3648.
PMID 10982887
 
Homozygous and compound heterozygous mutations at the Werner syndrome locus.
Oshima J, Yu CE, Piussan C, Klein G, Jabkowski J, Balci S, Miki T, Nakura J, Ogihara T, Ells J, Smith M, Melaragno MI, Fraccaro M, Scappaticci S, Matthews J, Ouais S, Jarzebowicz A, Schellenberg GD, Martin GM
Human molecular genetics. 1996 ; 5 (12) : 1909-1913.
PMID 8968742
 
Werner protein recruits DNA polymerase delta to the nucleolus.
Szekely AM, Chen YH, Zhang C, Oshima J, Weissman SM
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (21) : 11365-11370.
PMID 11027336
 
Werner syndrome and biological ageing: a molecular genetic hypothesis.
Thweatt R, Goldstein S
BioEssays : news and reviews in molecular, cellular and developmental biology. 1993 ; 15 (6) : 421-426.
PMID 8357345
 
Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts.
Wyllie FS, Jones CJ, Skinner JW, Haughton MF, Wallis C, Wynford-Thomas D, Faragher RG, Kipling D
Nature genetics. 2000 ; 24 (1) : 16-17.
PMID 10615119
 
Replication focus-forming activity 1 and the Werner syndrome gene product.
Yan H, Chen CY, Kobayashi R, Newport J
Nature genetics. 1998 ; 19 (4) : 375-378.
PMID 9697700
 
Positional cloning of the Werner's syndrome gene.
Yu CE, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, Matthews S, Nakura J, Miki T, Ouais S, Martin GM, Mulligan J, Schellenberg GD
Science (New York, N.Y.). 1996 ; 272 (5259) : 258-262.
PMID 8602509
 

Citation

This paper should be referenced as such :
Amor-Guéret, M
WRN (Werner syndrome, RecQ helicase-like)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):116-117.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/WRNID284.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ]

Solid Tumors TT_t0308p22p12ID106192 TT_t0308q29p12ID6884 TT_t0808p11p12ID108024 TT_t0808p12q11ID108046


Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Werner syndrome


External links

Nomenclature
HGNC (Hugo)WRN   12791
LRG (Locus Reference Genomic)LRG_524
Cards
AtlasWRNID284
Entrez_Gene (NCBI)WRN  7486  WRN RecQ like helicase
AliasesRECQ3; RECQL2; RECQL3
GeneCards (Weizmann)WRN
Ensembl hg19 (Hinxton)ENSG00000165392 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000165392 [Gene_View]  ENSG00000165392 [Sequence]  chr8:31033262-31175871 [Contig_View]  WRN [Vega]
ICGC DataPortalENSG00000165392
TCGA cBioPortalWRN
AceView (NCBI)WRN
Genatlas (Paris)WRN
WikiGenes7486
SOURCE (Princeton)WRN
Genetics Home Reference (NIH)WRN
Genomic and cartography
GoldenPath hg38 (UCSC)WRN  -     chr8:31033262-31175871 +  8p12   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)WRN  -     8p12   [Description]    (hg19-Feb_2009)
GoldenPathWRN - 8p12 [CytoView hg19]  WRN - 8p12 [CytoView hg38]
ImmunoBaseENSG00000165392
Mapping of homologs : NCBIWRN [Mapview hg19]  WRN [Mapview hg38]
OMIM277700   604611   
Gene and transcription
Genbank (Entrez)AB209652 AF091214 AL833572 AY818673 BP279291
RefSeq transcript (Entrez)NM_000553
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)WRN
Alternative Splicing GalleryENSG00000165392
Gene ExpressionWRN [ NCBI-GEO ]   WRN [ EBI - ARRAY_EXPRESS ]   WRN [ SEEK ]   WRN [ MEM ]
Gene Expression Viewer (FireBrowse)WRN [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)7486
GTEX Portal (Tissue expression)WRN
Human Protein AtlasENSG00000165392-WRN [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)WRN
DMDM Disease mutations7486
Blocks (Seattle)WRN
Human Protein Atlas [tissue]ENSG00000165392-WRN [tissue]
HPRD05212
IPIIPI00029107   
Protein Interaction databases
FunCoupENSG00000165392
BioGRIDWRN
STRING (EMBL)WRN
ZODIACWRN
Ontologies - Pathways
Huge Navigator WRN [HugePedia]
snp3D : Map Gene to Disease7486
BioCentury BCIQWRN
ClinGenWRN (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7486
Chemical/Pharm GKB GenePA367
Clinical trialWRN
Miscellaneous
canSAR (ICR)WRN (select the gene name)
DataMed IndexWRN
Other databasehttp://www.ncbi.nlm.nih.gov/cgi-bin/SCIENCE96/gene?WRN
Probes
Litterature
PubMed326 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineWRN
EVEXWRN
GoPubMedWRN
iHOPWRN
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Feb 19 16:29:14 CET 2020

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