WRN

Reviewed December 2012

What is the official name of the WRN gene?

The official name of this gene is “Werner syndrome, RecQ helicase-like.”

WRN is the gene's official symbol. The WRN gene is also known by other names, listed below.

What is the normal function of the WRN gene?

The WRN gene provides instructions for producing the Werner protein, which plays a critical role in repairing damaged DNA. The Werner protein functions as a type of enzyme called a helicase. Helicase enzymes generally unwind and separate double-stranded DNA. The Werner protein also functions as an enzyme called an exonuclease. Exonucleases trim the broken ends of damaged DNA by removing DNA building blocks (nucleotides). Research suggests that the Werner protein first unwinds the DNA and then removes abnormal DNA structures that have been accidentally generated.

Overall, the Werner protein helps maintain the structure and integrity of a person's DNA. This protein plays an important role in copying (replicating) DNA before cell division and transferring the information in genes to the cell machinery that makes proteins (transcription). Additionally, recent studies suggest that the Werner protein may be particularly important for maintaining DNA at the ends of chromosomes (telomeres).

How are changes in the WRN gene related to health conditions?

Werner syndrome - caused by mutations in the WRN gene: More than 60 mutations in the WRN gene are known to cause Werner syndrome. Most of these mutations result in an abnormally short, nonfunctional Werner protein. Research suggests that this shortened protein is not transported into the cell's nucleus, where it normally interacts with DNA. Furthermore, the shortened protein is broken down more quickly than the normal Werner protein, reducing the amount of this protein in the cell. Without normal Werner protein in the nucleus, DNA replication, repair, and transcription are disrupted. Researchers are still determining how mutations in the WRN gene lead to the signs and symptoms of Werner syndrome.
cancers - associated with the WRN gene: Some changes to a person's genes are acquired during that person's lifetime and are present only in certain cells. These differences, called somatic changes, are not inherited. Somatic changes in the WRN gene are found in nonhereditary tumors and involve a process called methylation. Methylation is a chemical modification that attaches small molecules called methyl groups to certain segments of DNA. When too many methyl groups are attached to the WRN gene (hypermethylation), the gene is turned off and the Werner protein is not produced. Without this protein, cells do not respond normally to DNA damage. The lack of Werner protein allows mutations to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. This kind of unregulated cell growth can lead to the formation of cancerous tumors. Hypermethylation of the WRN gene has been found in many different types of tumors, including colon, rectal, lung, stomach, prostate, breast, and thyroid tumors.

Where is the WRN gene located?

Cytogenetic Location: 8p12

Molecular Location on chromosome 8: base pairs 30,890,777 to 31,031,276

The WRN gene is located on the short (p) arm of chromosome 8 at position 12.

More precisely, the WRN gene is located from base pair 30,890,777 to base pair 31,031,276 on chromosome 8.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about WRN?

You and your healthcare professional may find the following resources about WRN helpful.

Educational resources - Information pages
Molecular Biology of the Cell (fourth edition, 2002): DNA Repair (http://www.ncbi.nlm.nih.gov/books/NBK26879/)
Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1514/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for WRN (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=7486%5Bgeneid%5D)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((WRN%5BTIAB%5D)%20OR%20(Werner%20syndrome%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20review%5Bpt%5D%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201080%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/604611)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_WRN.html)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/7486)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=7486)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=12791)
- Werner Syndrome Mutational Database (http://www.pathology.washington.edu/research/werner/database/)

What other names do people use for the WRN gene or gene products?

RECQ3
RECQL2
RECQL3
Werner syndrome
Werner Syndrome helicase
Werner syndrome protein
WRN_HUMAN

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding WRN?

cell ; cell division ; colon ; DNA ; DNA damage ; DNA replication ; enzyme ; gene ; helicase ; methyl ; methylation ; nucleus ; prostate ; protein ; stomach ; syndrome ; thyroid ; transcription

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Agrelo R, Cheng WH, Setien F, Ropero S, Espada J, Fraga MF, Herranz M, Paz MF, Sanchez-Cespedes M, Artiga MJ, Guerrero D, Castells A, von Kobbe C, Bohr VA, Esteller M. Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8822-7. Epub 2006 May 24. (http://www.ncbi.nlm.nih.gov/pubmed/16723399?dopt=Abstract)
Cheng WH, Muftuoglu M, Bohr VA. Werner syndrome protein: functions in the response to DNA damage and replication stress in S-phase. Exp Gerontol. 2007 Sep;42(9):871-8. Epub 2007 May 10. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17587522?dopt=Abstract)
Comai L, Li B. The Werner syndrome protein at the crossroads of DNA repair and apoptosis. Mech Ageing Dev. 2004 Aug;125(8):521-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15336909?dopt=Abstract)
Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/7486)
Futami K, Ishikawa Y, Goto M, Furuichi Y, Sugimoto M. Role of Werner syndrome gene product helicase in carcinogenesis and in resistance to genotoxins by cancer cells. Cancer Sci. 2008 May;99(5):843-8. doi: 10.1111/j.1349-7006.2008.00778.x. Epub 2008 Feb 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18312465?dopt=Abstract)
Gene Review: Werner Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1514/)
Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, Rubin CD, Chen DF, Yang CC, Juch H, Dorn T, Spiegel R, Oral EA, Abid M, Battisti C, Lucci-Cordisco E, Neri G, Steed EH, Kidd A, Isley W, Showalter D, Vittone JL, Konstantinow A, Ring J, Meyer P, Wenger SL, von Herbay A, Wollina U, Schuelke M, Huizenga CR, Leistritz DF, Martin GM, Mian IS, Oshima J. The spectrum of WRN mutations in Werner syndrome patients. Hum Mutat. 2006 Jun;27(6):558-67. (http://www.ncbi.nlm.nih.gov/pubmed/16673358?dopt=Abstract)
Kudlow BA, Kennedy BK, Monnat RJ Jr. Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nat Rev Mol Cell Biol. 2007 May;8(5):394-404. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17450177?dopt=Abstract)
Lee JW, Harrigan J, Opresko PL, Bohr VA. Pathways and functions of the Werner syndrome protein. Mech Ageing Dev. 2005 Jan;126(1):79-86. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15610765?dopt=Abstract)
Monnat RJ Jr, Saintigny Y. Werner syndrome protein--unwinding function to explain disease. Sci Aging Knowledge Environ. 2004 Mar 31;2004(13):re3. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15056797?dopt=Abstract)
OMIM: RECQ PROTEIN-LIKE 2 (http://omim.org/entry/604611)
Opresko PL, Calvo JP, von Kobbe C. Role for the Werner syndrome protein in the promotion of tumor cell growth. Mech Ageing Dev. 2007 Jul-Aug;128(7-8):423-36. Epub 2007 May 31. (http://www.ncbi.nlm.nih.gov/pubmed/17624410?dopt=Abstract)
Ozgenc A, Loeb LA. Current advances in unraveling the function of the Werner syndrome protein. Mutat Res. 2005 Sep 4;577(1-2):237-51. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15946710?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

WRN