The CTNNB1 gene provides instructions for making a protein called beta-catenin. This protein is present in many types of cells and tissues, where it is primarily found at junctions that connect neighboring cells (adherens junctions). Beta-catenin plays an important role in sticking cells together (cell adhesion) and in communication between cells.
The beta-catenin protein is also involved in cell signaling as an essential part of the Wnt signaling pathway. Certain proteins in this pathway attach (bind) to beta-catenin, which triggers a multistep process that allows the protein to move into the cell nucleus. Once in the nucleus, beta-catenin interacts with other proteins to control the activity (expression) of particular genes. The Wnt signaling pathway promotes the growth and division (proliferation) of cells and helps determine the specialized functions a cell will have (differentiation). Wnt signaling is known to be involved in many aspects of development before birth. In adult tissues, this pathway plays a role in the maintenance and renewal of stem cells, which are cells that help repair tissue damage and can give rise to other types of cells.
Among its many activities, beta-catenin appears to play an important role in the normal function of hair follicles, which are specialized structures in the skin where hair growth occurs. This protein is active in cells that make up a part of the hair follicle known as the matrix. These cells divide and mature to form the different components of the hair follicle and the hair shaft. As matrix cells divide, the hair shaft is pushed upward and extends beyond the skin.
Health Conditions Related to Genetic Changes
Mutations in the CTNNB1 gene can cause a type of aggressive but noncancerous (benign) growth called a desmoid tumor. CTNNB1 gene mutations are found in about 85 percent of all noninherited (sporadic) desmoid tumors. These rare tumors arise from connective tissue, which provides strength and flexibility to structures such as bones, ligaments, and muscles. The tumors are often found in the abdomen, shoulders, upper arms, or upper legs. The CTNNB1 gene mutations that cause desmoid tumors are somatic, which means they are acquired during a person's lifetime and are present only in tumor cells. Somatic mutations are not inherited.
The CTNNB1 gene mutations that cause desmoid tumors usually occur in a region of the gene called exon 3. They change single protein building blocks (amino acids) in the beta-catenin protein. These mutations lead to an abnormally stable beta-catenin protein that is not broken down when it is no longer needed. As a result, the protein accumulates within cells. Excess beta-catenin promotes the uncontrolled proliferation of cells, allowing the formation of desmoid tumors.More About This Health Condition
Somatic mutations in the CTNNB1 gene are found in almost all pilomatricomas, a type of benign skin tumor associated with hair follicles.
The CTNNB1 gene mutations found in pilomatricomas are described as gain-of-function mutations. They cause the beta-catenin protein to be turned on all the time (constitutively active), which leads to the abnormal activation of certain genes. These genes increase the proliferation and differentiation of cells associated with the hair follicle matrix. The cells divide too quickly and in an uncontrolled way, leading to the formation of a pilomatricoma.
Almost all pilomatricomas are benign, but a very small percentage are cancerous (malignant). The malignant version of this tumor is known as a pilomatrix carcinoma. Like pilomatricomas, pilomatrix carcinomas have somatic mutations in the CTNNB1 gene. It is unclear why some of these tumors are cancerous but most others are not.More About This Health Condition
Mutations in the CTNNB1 gene have been found in Wilms tumor, a rare form of kidney cancer that occurs almost exclusively in children. These mutations are somatic and occur only in kidney cells that give rise to the tumor. CTNNB1 gene mutations in Wilms tumor result in an overly active protein. This active beta-catenin protein promotes Wnt signaling longer than normal, which leads to the unchecked proliferation of kidney cells and tumor development.More About This Health Condition
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Somatic mutations in the CTNNB1 gene have been identified in several other types of cancer. These include colorectal, liver, thyroid, ovarian, endometrial, and skin cancers, as well as a type of brain tumor called a medulloblastoma, among others. Studies suggest that gain-of-function mutations in the CTNNB1 gene prevent the breakdown of beta-catenin when it is no longer needed, which allows the protein to accumulate within cells. The excess beta-catenin moves into the cell nucleus and promotes the unchecked proliferation of cells, allowing cancerous tumors to develop.
Because mutations in the CTNNB1 gene can cause normal cells to become cancerous, CTNNB1 belongs to a class of genes known as oncogenes. Sometimes, mutations in other oncogenes occur together with CTNNB1 gene mutations to cause cancer. It is not well understood why mutations in the CTNNB1 gene are associated with several different types of cancerous and noncancerous tumors.
Other Names for This Gene
- catenin (cadherin-associated protein), beta 1
- catenin (cadherin-associated protein), beta 1, 88kDa
- catenin beta-1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
- Al-Hussain T, Ali A, Akhtar M. Wilms tumor: an update. Adv Anat Pathol. 2014 May;21(3):166-73. doi: 10.1097/PAP.0000000000000017. Review. Citation on PubMed
- Barker N. The canonical Wnt/beta-catenin signalling pathway. Methods Mol Biol. 2008;468:5-15. doi: 10.1007/978-1-59745-249-6_1. Review. Citation on PubMed
- Chan EF, Gat U, McNiff JM, Fuchs E. A common human skin tumour is caused by activating mutations in beta-catenin. Nat Genet. 1999 Apr;21(4):410-3. Citation on PubMed
- Deng C, Dai R, Li X, Liu F. Genetic variation frequencies in Wilms' tumor: A meta-analysis and systematic review. Cancer Sci. 2016 May;107(5):690-9. doi: 10.1111/cas.12910. Epub 2016 Mar 18. Review. Citation on PubMed or Free article on PubMed Central
- Ferenc T, Wroński JW, Kopczyński J, Kulig A, Sidor M, Stalińska L, Dziki A, Sygut J. Analysis of APC, alpha-, beta-catenins, and N-cadherin protein expression in aggressive fibromatosis (desmoid tumor). Pathol Res Pract. 2009;205(5):311-24. doi: 10.1016/j.prp.2008.11.002. Epub 2009 Jan 4. Citation on PubMed
- Fu Y, Zheng S, An N, Athanasopoulos T, Popplewell L, Liang A, Li K, Hu C, Zhu Y. β-catenin as a potential key target for tumor suppression. Int J Cancer. 2011 Oct 1;129(7):1541-51. doi: 10.1002/ijc.26102. Epub 2011 Jun 21. Review. Citation on PubMed
- Huss S, Nehles J, Binot E, Wardelmann E, Mittler J, Kleine MA, Künstlinger H, Hartmann W, Hohenberger P, Merkelbach-Bruse S, Buettner R, Schildhaus HU. β-catenin (CTNNB1) mutations and clinicopathological features of mesenteric desmoid-type fibromatosis. Histopathology. 2013 Jan;62(2):294-304. doi: 10.1111/j.1365-2559.2012.04355.x. Epub 2012 Sep 28. Citation on PubMed
- Kajino Y, Yamaguchi A, Hashimoto N, Matsuura A, Sato N, Kikuchi K. beta-Catenin gene mutation in human hair follicle-related tumors. Pathol Int. 2001 Jul;51(7):543-8. Citation on PubMed
- Kotiligam D, Lazar AJ, Pollock RE, Lev D. Desmoid tumor: a disease opportune for molecular insights. Histol Histopathol. 2008 Jan;23(1):117-26. doi: 10.14670/HH-23.117. Review. Citation on PubMed
- Lazar AJ, Calonje E, Grayson W, Dei Tos AP, Mihm MC Jr, Redston M, McKee PH. Pilomatrix carcinomas contain mutations in CTNNB1, the gene encoding beta-catenin. J Cutan Pathol. 2005 Feb;32(2):148-57. Citation on PubMed
- Lips DJ, Barker N, Clevers H, Hennipman A. The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors). Eur J Surg Oncol. 2009 Jan;35(1):3-10. doi: 10.1016/j.ejso.2008.07.003. Epub 2008 Aug 21. Review. Citation on PubMed
- MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009 Jul;17(1):9-26. doi: 10.1016/j.devcel.2009.06.016. Review. Citation on PubMed or Free article on PubMed Central
- Moreno-Bueno G, Gamallo C, Pérez-Gallego L, Contreras F, Palacios J. beta-catenin expression in pilomatrixomas. Relationship with beta-catenin gene mutations and comparison with beta-catenin expression in normal hair follicles. Br J Dermatol. 2001 Oct;145(4):576-81. Citation on PubMed
- Tejpar S, Nollet F, Li C, Wunder JS, Michils G, dal Cin P, Van Cutsem E, Bapat B, van Roy F, Cassiman JJ, Alman BA. Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor). Oncogene. 1999 Nov 11;18(47):6615-20. Citation on PubMed
- Xia J, Urabe K, Moroi Y, Koga T, Duan H, Li Y, Furue M. beta-Catenin mutation and its nuclear localization are confirmed to be frequent causes of Wnt signaling pathway activation in pilomatricomas. J Dermatol Sci. 2006 Jan;41(1):67-75. Epub 2005 Dec 27. Citation on PubMed