WRN (Werner syndrome, RecQ helicase-like)

2001-03-01 Mounira Amor-Guéret Affiliation

Institut Curie - Section de Recherche, UMR 2027 CNRS, Bâtiment 110, Centre Universitaire, F-91405 Orsay Cedex, France

Identity

HGNC

WRN

LOCATION

8p12

LOCUSID

7486

ALIAS

RECQ3,RECQL2,RECQL3

FUSION GENES

Show Gene Fusions

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

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

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)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Metabolism of proteins	REACTOME	R-HSA-392499
Post-translational protein modification	REACTOME	R-HSA-597592
SUMOylation	REACTOME	R-HSA-2990846
SUMO E3 ligases SUMOylate target proteins	REACTOME	R-HSA-3108232
SUMOylation of DNA damage response and repair proteins	REACTOME	R-HSA-3108214
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Transcriptional Regulation by TP53	REACTOME	R-HSA-3700989
Cell Cycle	REACTOME	R-HSA-1640170
Cell Cycle Checkpoints	REACTOME	R-HSA-69620
G2/M Checkpoints	REACTOME	R-HSA-69481
G2/M DNA damage checkpoint	REACTOME	R-HSA-69473
DNA Repair	REACTOME	R-HSA-73894
DNA Double-Strand Break Repair	REACTOME	R-HSA-5693532
Homology Directed Repair	REACTOME	R-HSA-5693538
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)	REACTOME	R-HSA-5693567
Processing of DNA double-strand break ends	REACTOME	R-HSA-5693607
HDR through Homologous Recombination (HRR)	REACTOME	R-HSA-5685942
Homologous DNA Pairing and Strand Exchange	REACTOME	R-HSA-5693579
Presynaptic phase of homologous DNA pairing and strand exchange	REACTOME	R-HSA-5693616
Resolution of D-Loop Structures	REACTOME	R-HSA-5693537
Resolution of D-loop Structures through Holliday Junction Intermediates	REACTOME	R-HSA-5693568
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	REACTOME	R-HSA-5693554
HDR through Single Strand Annealing (SSA)	REACTOME	R-HSA-5685938
Regulation of TP53 Activity	REACTOME	R-HSA-5633007
Regulation of TP53 Activity through Phosphorylation	REACTOME	R-HSA-6804756

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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-%28werner-syndrome-recq-helicase-like%29