ITGB4 Gene: History
Please note this is an old version of this entry, which may differ significantly from the current revision.

Integrin subunit beta 4

  • genes

1. Introduction

The ITGB4 gene provides instructions for making one part (the β4 subunit) of a protein known as an integrin. Integrins are a group of proteins that regulate the attachment of cells to one another (cell-cell adhesion) and to the surrounding network of proteins and other molecules (cell-matrix adhesion). Integrins also transmit chemical signals that regulate cell growth and the activity of certain genes.

The integrin protein made with the β4 subunit is known as α6β4 integrin. This protein is found primarily in epithelial cells, which are cells that line the surfaces and cavities of the body. The α6β4 integrin protein plays a particularly important role in strengthening and stabilizing the skin. It is a component of hemidesmosomes, which are microscopic structures that anchor the outer layer of the skin (the epidermis) to underlying layers. As part of a complex network of proteins in hemidesmosomes, α6β4 integrin helps to hold the layers of skin together.

2. Health Conditions Related to Genetic Changes

2.1. Epidermolysis Bullosa with Pyloric Atresia

At least 60 mutations in the ITGB4 gene have been found to cause epidermolysis bullosa with pyloric atresia (EB-PA). In addition to skin blistering, people with EB-PA are born with a life-threatening obstruction of the digestive tract called pyloric atresia. Mutations in the ITGB4 gene account for about 80 percent of all cases of EB-PA.

ITGB4 gene mutations alter the normal structure and function of the β4 integrin subunit or prevent cells from producing enough of this subunit. As a result, α6β4 integrin is defective or missing. Mutations that lead to a complete or near-complete loss of α6β4 integrin tend to cause more severe signs and symptoms of EB-PA, while mutations that alter the structure or stability of this protein usually cause milder signs and symptoms. A shortage of functional α6β4 integrin causes cells in the epidermis to be fragile and easily damaged. Friction or other minor trauma can cause the skin layers to separate, leading to the widespread formation of blisters. It is less clear how mutations in the ITGB4 gene are related to pyloric atresia.

2.2. Cancers

Researchers believe that α6β4 integrin may play a critical role in the progression of cancerous tumors called carcinomas. These cancers arise in epithelial cells and can affect many tissues and organs, including the breast, lung, liver, colon, and skin.

Changes in the location and activity of α6β4 integrin within cancer cells are associated with the progression of carcinomas. The integrin protein activates key signaling molecules, which trigger cancer cells to migrate through the body and invade other tissues. These signals also make cancer cells more resistant to self-destruction (apoptosis).

Recent studies suggest that, in addition to its role in the progression of existing carcinomas, α6β4 integrin may be involved in the initial formation of these tumors.

3. Other Names for This Gene

  • CD104

  • CD104 antigen

  • GP150

  • integrin beta 4

  • Integrin beta(4)

  • integrin beta-4 subunit

  • Integrin beta4

  • integrin, beta 4

  • integrin, beta-4


  • Lymphocyte antigen CD104

This entry is adapted from the peer-reviewed paper


  1. Ashton GH, Sorelli P, Mellerio JE, Keane FM, Eady RA, McGrath JA. Alpha 6 beta4 integrin abnormalities in junctional epidermolysis bullosa with pyloricatresia. Br J Dermatol. 2001 Feb;144(2):408-14.
  2. Dang N, Klingberg S, Rubin AI, Edwards M, Borelli S, Relic J, Marr P, Tran K, Turner A, Smith N, Murrell DF. Differential expression of pyloric atresia injunctional epidermolysis bullosa with ITGB4 mutations suggests that pyloricatresia is due to factors other than the mutations and not predictive of a pooroutcome: three novel mutations and a review of the literature. Acta DermVenereol. 2008;88(5):438-48. doi: 10.2340/00015555-0484. Review.
  3. Guo W, Pylayeva Y, Pepe A, Yoshioka T, Muller WJ, Inghirami G, Giancotti FG.Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell.2006 Aug 11;126(3):489-502.
  4. Lipscomb EA, Mercurio AM. Mobilization and activation of a signaling competentalpha6beta4integrin underlies its contribution to carcinoma progression. CancerMetastasis Rev. 2005 Sep;24(3):413-23. Review.
  5. Nakano A, Pulkkinen L, Murrell D, Rico J, Lucky AW, Garzon M, Stevens CA,Robertson S, Pfendner E, Uitto J. Epidermolysis bullosa with congenital pyloricatresia: novel mutations in the beta 4 integrin gene (ITGB4) andgenotype/phenotype correlations. Pediatr Res. 2001 May;49(5):618-26.
  6. Pulkkinen L, Kim DU, Uitto J. Epidermolysis bullosa with pyloric atresia:novel mutations in the beta4 integrin gene (ITGB4). Am J Pathol. 1998Jan;152(1):157-66.
  7. Pulkkinen L, Rouan F, Bruckner-Tuderman L, Wallerstein R, Garzon M, Brown T,Smith L, Carter W, Uitto J. Novel ITGB4 mutations in lethal and nonlethalvariants of epidermolysis bullosa with pyloric atresia: missense versus nonsense.Am J Hum Genet. 1998 Nov;63(5):1376-87.
  8. Yoon SO, Shin S, Lipscomb EA. A novel mechanism for integrin-mediated rasactivation in breast carcinoma cells: the alpha6beta4 integrin regulates ErbB2translation and transactivates epidermal growth factor receptor/ErbB2 signaling. Cancer Res. 2006 Mar 1;66(5):2732-9.
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