Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

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

HGNC (Hugo) WRN
LocusID (NCBI) 7486
Atlas_Id 284
Location 8p12  [Link to chromosome band 8p12]
Location_base_pair Starts at 30890778 and ends at 31031277 bp from pter ( according to hg19-Feb_2009)  [Mapping WRN.png]
Fusion genes
(updated 2016)
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 Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  Chronic myelogenous leukaemia (CML)

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 0 ]
  Lung: Translocations in Squamous Cell Carcinoma

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

External links

Nomenclature
HGNC (Hugo)WRN   12791
Cards
AtlasWRNID284
Entrez_Gene (NCBI)WRN  7486  Werner syndrome RecQ like helicase
AliasesRECQ3; RECQL2; RECQL3
GeneCards (Weizmann)WRN
Ensembl hg19 (Hinxton)ENSG00000165392 [Gene_View]  chr8:30890778-31031277 [Contig_View]  WRN [Vega]
Ensembl hg38 (Hinxton)ENSG00000165392 [Gene_View]  chr8:30890778-31031277 [Contig_View]  WRN [Vega]
ICGC DataPortalENSG00000165392
TCGA cBioPortalWRN
AceView (NCBI)WRN
Genatlas (Paris)WRN
WikiGenes7486
SOURCE (Princeton)WRN
Genomic and cartography
GoldenPath hg19 (UCSC)WRN  -     chr8:30890778-31031277 +  8p12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)WRN  -     8p12   [Description]    (hg38-Dec_2013)
EnsemblWRN - 8p12 [CytoView hg19]  WRN - 8p12 [CytoView hg38]
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)NC_000008 NC_018919 NG_008870 NT_167187 NW_004929337
Consensus coding sequences : CCDS (NCBI)WRN
Cluster EST : UnigeneHs.632050 [ NCBI ]
CGAP (NCI)Hs.632050
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]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7486
GTEX Portal (Tissue expression)WRN
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ14191 (Uniprot)
NextProtQ14191  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ14191
Splice isoforms : SwissVarQ14191 (Swissvar)
Catalytic activity : Enzyme3.1.-.- [ Enzyme-Expasy ]   3.1.-.-3.1.-.- [ IntEnz-EBI ]   3.1.-.- [ BRENDA ]   3.1.-.- [ KEGG ]   
PhosPhoSitePlusQ14191
Domaine pattern : Prosite (Expaxy)HELICASE_ATP_BIND_1 (PS51192)    HELICASE_CTER (PS51194)    HRDC (PS50967)   
Domains : Interpro (EBI)3'-5'_exonuclease_dom    DEAD/DEAH_box_helicase_dom    DNA_helicase_ATP-dep_RecQ    Helicase_ATP-bd    Helicase_C    Helicase_HTH    HRDC-like    HRDC_dom    P-loop_NTPase    RecQ_Zn-bd    RNaseH-like_dom    RQC_domain    WHTH_DNA-bd_dom   
Domain families : Pfam (Sanger)DEAD (PF00270)    DNA_pol_A_exo1 (PF01612)    Helicase_C (PF00271)    HRDC (PF00570)    HTH_40 (PF14493)    RecQ_Zn_bind (PF16124)    RQC (PF09382)   
Domain families : Pfam (NCBI)pfam00270    pfam01612    pfam00271    pfam00570    pfam14493    pfam16124    pfam09382   
Domain families : Smart (EMBL)35EXOc (SM00474)  DEXDc (SM00487)  HELICc (SM00490)  HRDC (SM00341)  RQC (SM00956)  
DMDM Disease mutations7486
Blocks (Seattle)WRN
PDB (SRS)2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0    3AAF   
PDB (PDBSum)2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0    3AAF   
PDB (IMB)2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0    3AAF   
PDB (RSDB)2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0    3AAF   
Structural Biology KnowledgeBase2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0    3AAF   
SCOP (Structural Classification of Proteins)2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0    3AAF   
CATH (Classification of proteins structures)2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0    3AAF   
SuperfamilyQ14191
Human Protein AtlasENSG00000165392
Peptide AtlasQ14191
HPRD05212
IPIIPI00029107   
Protein Interaction databases
DIP (DOE-UCLA)Q14191
IntAct (EBI)Q14191
FunCoupENSG00000165392
BioGRIDWRN
STRING (EMBL)WRN
ZODIACWRN
Ontologies - Pathways
QuickGOQ14191
Ontology : AmiGOmagnesium ion binding  Y-form DNA binding  bubble DNA binding  telomere maintenance via recombination  telomere maintenance  DNA synthesis involved in DNA repair  DNA synthesis involved in DNA repair  strand displacement  nuclear chromosome, telomeric region  replicative cell aging  DNA binding  DNA helicase activity  DNA helicase activity  chromatin binding  ATP-dependent DNA helicase activity  helicase activity  exonuclease activity  protein binding  ATP binding  nucleoplasm  nucleoplasm  nucleolus  cytoplasm  centrosome  DNA metabolic process  DNA replication  DNA replication  base-excision repair  double-strand break repair  cellular response to DNA damage stimulus  response to oxidative stress  brain development  aging  cell aging  3'-5' exonuclease activity  cellular response to starvation  four-way junction helicase activity  response to UV-C  multicellular organism aging  ATPase activity  protein sumoylation  manganese ion binding  replication fork processing  replication fork processing  nucleolus to nucleoplasm transport  MutLalpha complex  protein complex binding  DNA duplex unwinding  DNA duplex unwinding  DNA duplex unwinding  DNA duplex unwinding  regulation of growth rate  protein homodimerization activity  regulation of apoptotic process  neuron projection  3'-5' DNA helicase activity  ATP-dependent 3'-5' DNA helicase activity  positive regulation of hydrolase activity  G-quadruplex DNA binding  cellular response to gamma radiation  nucleic acid phosphodiester bond hydrolysis  nucleic acid phosphodiester bond hydrolysis  regulation of signal transduction by p53 class mediator  
Ontology : EGO-EBImagnesium ion binding  Y-form DNA binding  bubble DNA binding  telomere maintenance via recombination  telomere maintenance  DNA synthesis involved in DNA repair  DNA synthesis involved in DNA repair  strand displacement  nuclear chromosome, telomeric region  replicative cell aging  DNA binding  DNA helicase activity  DNA helicase activity  chromatin binding  ATP-dependent DNA helicase activity  helicase activity  exonuclease activity  protein binding  ATP binding  nucleoplasm  nucleoplasm  nucleolus  cytoplasm  centrosome  DNA metabolic process  DNA replication  DNA replication  base-excision repair  double-strand break repair  cellular response to DNA damage stimulus  response to oxidative stress  brain development  aging  cell aging  3'-5' exonuclease activity  cellular response to starvation  four-way junction helicase activity  response to UV-C  multicellular organism aging  ATPase activity  protein sumoylation  manganese ion binding  replication fork processing  replication fork processing  nucleolus to nucleoplasm transport  MutLalpha complex  protein complex binding  DNA duplex unwinding  DNA duplex unwinding  DNA duplex unwinding  DNA duplex unwinding  regulation of growth rate  protein homodimerization activity  regulation of apoptotic process  neuron projection  3'-5' DNA helicase activity  ATP-dependent 3'-5' DNA helicase activity  positive regulation of hydrolase activity  G-quadruplex DNA binding  cellular response to gamma radiation  nucleic acid phosphodiester bond hydrolysis  nucleic acid phosphodiester bond hydrolysis  regulation of signal transduction by p53 class mediator  
REACTOMEQ14191 [protein]
REACTOME PathwaysR-HSA-3108214 SUMOylation of DNA damage response and repair proteins [pathway]
NDEx NetworkWRN
Atlas of Cancer Signalling NetworkWRN
Wikipedia pathwaysWRN
Orthology - Evolution
OrthoDB7486
GeneTree (enSembl)ENSG00000165392
Phylogenetic Trees/Animal Genes : TreeFamWRN
Homologs : HomoloGeneWRN
Homology/Alignments : Family Browser (UCSC)WRN
Gene fusions - Rearrangements
Fusion : MitelmanCTDSPL/WRN [3p22.2/8p12]  [t(3;8)(p22;p12)]  
Fusion : MitelmanPCMTD1/WRN [8q11.23/8p12]  [t(8;8)(p12;q11)]  
Fusion : MitelmanWRN/ADAM9 [8p12/8p11.22]  [t(8;8)(p11;p12)]  
Fusion: TCGACTDSPL 3p22.2 WRN 8p12 BLCA
Fusion: TCGAPCMTD1 8q11.23 WRN 8p12 BRCA
Fusion: TCGAWRN 8p12 ADAM9 8p11.22 BRCA
Polymorphisms : SNP, variants
NCBI Variation ViewerWRN [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)WRN
dbVarWRN
ClinVarWRN
1000_GenomesWRN 
Exome Variant ServerWRN
ExAC (Exome Aggregation Consortium)WRN (select the gene name)
Genetic variants : HAPMAP7486
Genomic Variants (DGV)WRN [DGVbeta]
Mutations
ICGC Data PortalWRN 
TCGA Data PortalWRN 
Broad Tumor PortalWRN
OASIS PortalWRN [ Somatic mutations - Copy number]
Cancer Gene: CensusWRN 
Somatic Mutations in Cancer : COSMICWRN 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch WRN
DgiDB (Drug Gene Interaction Database)WRN
DoCM (Curated mutations)WRN (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)WRN (select a term)
intoGenWRN
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)8:30890778-31031277  ENSG00000165392
CONAN: Copy Number AnalysisWRN 
OrphanetWerner syndrome
Mutations and Diseases : HGMDWRN
OMIM277700    604611   
MedgenWRN
Genetic Testing Registry WRN
NextProtQ14191 [Medical]
TSGene7486
GENETestsWRN
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)
Other databasehttp://www.ncbi.nlm.nih.gov/cgi-bin/SCIENCE96/gene?WRN
Probes
Litterature
PubMed271 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

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Sep 28 15:58:02 CEST 2016

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.