The TNXB gene provides instructions for making a protein called tenascin-X. This protein plays an important role in organizing and maintaining the structure of tissues that support the body's muscles, joints, organs, and skin (connective tissues). In particular, studies suggest that it helps to regulate the production and assembly of certain types of collagen. Collagens are a family of proteins that strengthen and support connective tissues throughout the body. Tenascin-X is also involved in regulating the structure and stability of elastic fibers, which provide flexibility and stretchiness (elasticity) to connective tissues.
Health Conditions Related to Genetic Changes
Mutations in the TNXB gene cause a very small percentage of all cases of a form of Ehlers-Danlos syndrome called the hypermobile type. Ehlers-Danlos syndrome is a group of disorders that affect the connective tissues that support the skin, bones, blood vessels, and many other organs and tissues. The hypermobile type is characterized by an unusually large range of joint movement (hypermobility). The mutations that cause this form of the disorder occur in one copy of the TNXB gene in each cell. These mutations reduce the amount of functional tenascin-X that cells produce, which decreases the ability of tenascin-X to interact with collagens and elastic fibers. These changes weaken connective tissues in many parts of the body, which results in the signs and symptoms of the hypermobile type of Ehlers-Danlos syndrome.
Some people with a condition called benign joint hypermobility syndrome (BJHS) also make a reduced amount of tenascin-X protein, although no TNXB gene mutations have been identified in these individuals. This condition causes hypermobility and chronic joint pain. The signs and symptoms of benign joint hypermobility syndrome overlap significantly with those of the hypermobile type of Ehlers-Danlos syndrome. Studies suggest that they may be forms of the same condition.
Some people with Ehlers-Danlos syndrome have mutations in two copies of the TNXB gene in each cell. These individuals have a form of the disorder that is often called the classical-like type. Its signs and symptoms are similar to the classical type of Ehlers-Danlos syndrome, including hypermobility and skin that is soft, highly stretchy (elastic), and fragile. However, affected individuals do not have the unusual scarring that is characteristic of that type. Mutations that occur in both copies of the TNXB gene prevent production of any tenascin-X protein. A loss of this protein severely disrupts the organization of collagen fibrils and elastic fibers, which significantly weakens connective tissues.More About This Health Condition
Other Names for This Gene
- tenascin XB1
- tenascin XB2
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Demirdas S, Dulfer E, Robert L, Kempers M, van Beek D, Micha D, van Engelen BG, Hamel B, Schalkwijk J, Loeys B, Maugeri A, Voermans NC. Recognizing the tenascin-X deficient type of Ehlers-Danlos syndrome: a cross-sectional study in 17 patients. Clin Genet. 2017 Mar;91(3):411-425. doi: 10.1111/cge.12853. Epub 2016 Nov 4. Citation on PubMed
- Hendriks AGM, Voermans NC, Schalkwijk J, Hamel BC, van Rossum MM. Well-defined clinical presentation of Ehlers-Danlos syndrome in patients with tenascin-X deficiency: a report of four cases. Clin Dysmorphol. 2012 Jan;21(1):15-18. doi: 10.1097/MCD.0b013e32834c4bb7. Citation on PubMed
- Lindor NM, Bristow J. Tenascin-X deficiency in autosomal recessive Ehlers-Danlos syndrome. Am J Med Genet A. 2005 May 15;135(1):75-80. doi: 10.1002/ajmg.a.30671. Citation on PubMed
- Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, Bloom L, Bowen JM, Brady AF, Burrows NP, Castori M, Cohen H, Colombi M, Demirdas S, De Backer J, De Paepe A, Fournel-Gigleux S, Frank M, Ghali N, Giunta C, Grahame R, Hakim A, Jeunemaitre X, Johnson D, Juul-Kristensen B, Kapferer-Seebacher I, Kazkaz H, Kosho T, Lavallee ME, Levy H, Mendoza-Londono R, Pepin M, Pope FM, Reinstein E, Robert L, Rohrbach M, Sanders L, Sobey GJ, Van Damme T, Vandersteen A, van Mourik C, Voermans N, Wheeldon N, Zschocke J, Tinkle B. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):8-26. doi: 10.1002/ajmg.c.31552. Citation on PubMed
- Schalkwijk J, Zweers MC, Steijlen PM, Dean WB, Taylor G, van Vlijmen IM, van Haren B, Miller WL, Bristow J. A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency. N Engl J Med. 2001 Oct 18;345(16):1167-75. doi: 10.1056/NEJMoa002939. Citation on PubMed
- Tinkle B, Castori M, Berglund B, Cohen H, Grahame R, Kazkaz H, Levy H. Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and natural history. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):48-69. doi: 10.1002/ajmg.c.31538. Epub 2017 Feb 1. Citation on PubMed
- Valcourt U, Alcaraz LB, Exposito JY, Lethias C, Bartholin L. Tenascin-X: beyond the architectural function. Cell Adh Migr. 2015;9(1-2):154-65. doi: 10.4161/19336918.2014.994893. Citation on PubMed or Free article on PubMed Central
- van Dijk FS, Ghali N, Demirdas S, Baker D. TNXB-Related Classical-Like Ehlers-Danlos Syndrome. 2022 Sep 15. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK584019/ Citation on PubMed
- Voermans NC, Jenniskens GJ, Hamel BC, Schalkwijk J, Guicheney P, van Engelen BG. Ehlers-Danlos syndrome due to tenascin-X deficiency: muscle weakness and contractures support overlap with collagen VI myopathies. Am J Med Genet A. 2007 Sep 15;143A(18):2215-9. doi: 10.1002/ajmg.a.31899. No abstract available. Citation on PubMed
- Zweers MC, Bristow J, Steijlen PM, Dean WB, Hamel BC, Otero M, Kucharekova M, Boezeman JB, Schalkwijk J. Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome. Am J Hum Genet. 2003 Jul;73(1):214-7. doi: 10.1086/376564. No abstract available. Citation on PubMed or Free article on PubMed Central
- Zweers MC, Dean WB, van Kuppevelt TH, Bristow J, Schalkwijk J. Elastic fiber abnormalities in hypermobility type Ehlers-Danlos syndrome patients with tenascin-X mutations. Clin Genet. 2005 Apr;67(4):330-4. doi: 10.1111/j.1399-0004.2005.00401.x. Citation on PubMed
- Zweers MC, Hakim AJ, Grahame R, Schalkwijk J. Joint hypermobility syndromes: the pathophysiologic role of tenascin-X gene defects. Arthritis Rheum. 2004 Sep;50(9):2742-9. doi: 10.1002/art.20488. No abstract available. Citation on PubMed