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Genetics Home Reference: your guide to understanding genetic conditions
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CYLD

Reviewed June 2012

What is the official name of the CYLD gene?

The official name of this gene is “cylindromatosis (turban tumor syndrome).”

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

What is the normal function of the CYLD gene?

The CYLD gene provides instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins that help protect cells from self-destruction (apoptosis) in response to certain signals. In regulating the action of nuclear factor-kappa-B, the CYLD protein allows cells to respond properly to signals to self-destruct when appropriate, such as when the cells become abnormal. By this mechanism, the CYLD protein acts as a tumor suppressor, which means that it helps prevent cells from growing and dividing too fast or in an uncontrolled way.

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

Brooke-Spiegler syndrome - caused by mutations in the CYLD gene

At least 20 CYLD gene mutations have been identified in individuals with Brooke-Spiegler syndrome. This condition is characterized by multiple noncancerous (benign) tumors that develop in structures associated with the skin (skin appendages), such as sweat glands and hair follicles. People with Brooke-Spiegler syndrome may develop several types of skin appendage tumors, including growths called spiradenomas, trichoepitheliomas, and cylindromas. Spiradenomas are tumors of the sweat glands. Trichoepitheliomas arise from the hair follicles. While previously thought to derive from sweat glands, cylindromas are now generally believed to begin in hair follicles.

People with Brooke-Spiegler syndrome are born with a mutation in one of the two copies of the CYLD gene in each cell. This mutation prevents the cell from making functional CYLD protein from the altered copy of the gene. However, enough protein is usually produced from the other, normal copy of the gene to regulate cell growth effectively. For tumors to develop, a second mutation or deletion of genetic material involving the other copy of the CYLD gene must occur in certain cells during a person's lifetime. These genetic changes are called somatic mutations and are not inherited.

When both copies of the CYLD gene are mutated in a particular cell, that cell cannot produce any functional CYLD protein. The loss of this protein impairs the regulation of nuclear factor-kappa-B, allowing the cell to grow and divide in an uncontrolled way to form a tumor. In people with Brooke-Spiegler syndrome, second CYLD mutations typically occur in different types of cells in the skin over an affected person's lifetime, leading to the growth of multiple types of skin appendage tumors.

familial cylindromatosis - caused by mutations in the CYLD gene

More than 30 CYLD gene mutations have been identified in individuals with familial cylindromatosis. People with this disorder typically develop large numbers of cylindromas.

As in Brooke-Spiegler syndrome, people with familial cylindromatosis are born with one mutated copy of the CYLD gene in each cell, and a second mutation or deletion of genetic material involving the other copy of the CYLD gene must occur in certain cells during a person's lifetime.

When both copies of the CYLD gene are mutated in particular hair follicle cells, those cells cannot produce any functional CYLD protein. The loss of this protein allows the cells to grow and divide in an uncontrolled way to form cylindromas.

multiple familial trichoepithelioma - caused by mutations in the CYLD gene

At least 22 mutations in the CYLD gene have been identified in individuals with multiple familial trichoepithelioma. People with this disorder typically develop large numbers of trichoepitheliomas.

As in Brooke-Spiegler syndrome and familial cylindromatosis, people with CYLD-related multiple familial trichoepithelioma are born with one mutated copy of the CYLD gene in each cell, and a second mutation or deletion of genetic material involving the other copy of the CYLD gene must occur in certain cells during a person's lifetime.

When both copies of the CYLD gene are mutated in particular hair follicle cells, those cells cannot produce any functional CYLD protein. The loss of this protein allows the cells to grow and divide in an uncontrolled way to form trichoepitheliomas.

Some researchers consider familial cylindromatosis, multiple familial trichoepithelioma, and Brooke-Spiegler syndrome to be different forms of the same disorder. It is unclear why mutations in the CYLD gene cause different types of skin appendage tumors in each of these conditions, or why the tumors are generally confined to the skin in these disorders.

cancers - associated with the CYLD gene

Somatic mutations and reduced activity (expression) of the CYLD gene have also been identified in certain cancerous tumors. These cancers include multiple myeloma, which starts in cells of the bone marrow, and cancers of the kidney, liver, uterus, and colon. These genetic changes likely impair the tumor suppressor function of the CYLD protein, allowing cells to grow and divide in an uncontrolled way and become cancerous.

Where is the CYLD gene located?

Cytogenetic Location: 16q12.1

Molecular Location on chromosome 16: base pairs 50,742,049 to 50,801,935

The CYLD gene is located on the long (q) arm of chromosome 16 at position 12.1.

The CYLD gene is located on the long (q) arm of chromosome 16 at position 12.1.

More precisely, the CYLD gene is located from base pair 50,742,049 to base pair 50,801,935 on chromosome 16.

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 CYLD?

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

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

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

  • BRSS
  • CDMT
  • CYLD1
  • CYLD_HUMAN
  • CYLDI
  • EAC
  • HSPC057
  • KIAA0849
  • MFT
  • MFT1
  • SBS
  • TEM
  • USPL2

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 CYLD?

apoptosis ; benign ; bone marrow ; cell ; colon ; deletion ; familial ; gene ; hair follicle ; inherited ; kidney ; multiple myeloma ; mutation ; myeloma ; protein ; syndrome ; tumor

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

References

  • Alameda JP, Fernández-Aceñero MJ, Moreno-Maldonado R, Navarro M, Quintana R, Page A, Ramírez A, Bravo A, Casanova ML. CYLD regulates keratinocyte differentiation and skin cancer progression in humans. Cell Death Dis. 2011 Sep 8;2:e208. doi: 10.1038/cddis.2011.82. (http://www.ncbi.nlm.nih.gov/pubmed/21900959?dopt=Abstract)
  • Almeida S, Maillard C, Itin P, Hohl D, Huber M. Five new CYLD mutations in skin appendage tumors and evidence that aspartic acid 681 in CYLD is essential for deubiquitinase activity. J Invest Dermatol. 2008 Mar;128(3):587-93. Epub 2007 Sep 13. (http://www.ncbi.nlm.nih.gov/pubmed/17851586?dopt=Abstract)
  • Bignell GR, Warren W, Seal S, Takahashi M, Rapley E, Barfoot R, Green H, Brown C, Biggs PJ, Lakhani SR, Jones C, Hansen J, Blair E, Hofmann B, Siebert R, Turner G, Evans DG, Schrander-Stumpel C, Beemer FA, van Den Ouweland A, Halley D, Delpech B, Cleveland MG, Leigh I, Leisti J, Rasmussen S. Identification of the familial cylindromatosis tumour-suppressor gene. Nat Genet. 2000 Jun;25(2):160-5. (http://www.ncbi.nlm.nih.gov/pubmed/10835629?dopt=Abstract)
  • Blake PW, Toro JR. Update of cylindromatosis gene (CYLD) mutations in Brooke-Spiegler syndrome: novel insights into the role of deubiquitination in cell signaling. Hum Mutat. 2009 Jul;30(7):1025-36. doi: 10.1002/humu.21024. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19462465?dopt=Abstract)
  • OMIM: CYLD GENE (http://omim.org/entry/605018)
  • Lee DA, Grossman ME, Schneiderman P, Celebi JT. Genetics of skin appendage neoplasms and related syndromes. J Med Genet. 2005 Nov;42(11):811-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16272260?dopt=Abstract)
  • Massoumi R, Paus R. Cylindromatosis and the CYLD gene: new lessons on the molecular principles of epithelial growth control. Bioessays. 2007 Dec;29(12):1203-14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18008375?dopt=Abstract)
  • Massoumi R. CYLD: a deubiquitination enzyme with multiple roles in cancer. Future Oncol. 2011 Feb;7(2):285-97. doi: 10.2217/fon.10.187. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21345146?dopt=Abstract)
  • Massoumi R. Ubiquitin chain cleavage: CYLD at work. Trends Biochem Sci. 2010 Jul;35(7):392-9. doi: 10.1016/j.tibs.2010.02.007. Epub 2010 Mar 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20347313?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1540)
  • Saggar S, Chernoff KA, Lodha S, Horev L, Kohl S, Honjo RS, Brandt HR, Hartmann K, Celebi JT. CYLD mutations in familial skin appendage tumours. J Med Genet. 2008 May;45(5):298-302. doi: 10.1136/jmg.2007.056127. Epub 2008 Jan 30. (http://www.ncbi.nlm.nih.gov/pubmed/18234730?dopt=Abstract)
  • Sun SC. CYLD: a tumor suppressor deubiquitinase regulating NF-kappaB activation and diverse biological processes. Cell Death Differ. 2010 Jan;17(1):25-34. doi: 10.1038/cdd.2009.43. Epub . Review. (http://www.ncbi.nlm.nih.gov/pubmed/19373246?dopt=Abstract)
  • Young AL, Kellermayer R, Szigeti R, Tészás A, Azmi S, Celebi JT. CYLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes. Clin Genet. 2006 Sep;70(3):246-9. (http://www.ncbi.nlm.nih.gov/pubmed/16922728?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.

 
Reviewed: June 2012
Published: September 15, 2014