Skip navigation

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

URL of this page: https://medlineplus.gov/genetics/gene/lama3/

LAMA3 gene

laminin subunit alpha 3

Normal Function

The LAMA3 gene provides instructions for making one part (subunit) of a protein called laminin 332 (formerly known as laminin 5). This protein is made up of three subunits, called alpha, beta, and gamma. The LAMA3 gene carries instructions for the alpha subunit; the beta and gamma subunits are produced from other genes. Three versions of the alpha subunit, called alpha-3a, alpha-3b1, and alpha-3b2, are produced from the LAMA3 gene.

Laminins are a group of proteins that regulate cell growth, cell movement (motility), and the attachment of cells to one another (adhesion). They are also involved in the formation and organization of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. Laminin 332 has a particularly important role in the basement membrane that underlies the top layer of skin (the epidermis). This membrane gives strength and resiliency to the skin and creates an additional barrier between the body and its surrounding environment. Laminin 332 is a major component of fibers called anchoring filaments, which connect the two layers of the basement membrane and help hold the skin together.

Studies suggest that laminin 332 also has several other functions. This protein appears to be important in the formation of early wound-healing tissues. Additionally, researchers have proposed roles for laminin 332 in the clear outer covering of the eye (the cornea) and in the development of tooth enamel.

The alpha subunit produced from the LAMA3 gene is also part of two other laminin proteins, laminin 311 and laminin 321. These laminins also appear to provide strength to the skin, although they do not play as big a role as laminin 332. In addition, laminin 311 is involved in cell signaling in the lungs and other tissues.

Health Conditions Related to Genetic Changes

Junctional epidermolysis bullosa

At least 50 mutations in the LAMA3 gene have been identified in people with junctional epidermolysis bullosa (JEB). The more serious form of the disease, known as JEB generalized severe, usually results from mutations that prevent the production of functional laminin 332. Most of these mutations lead to a premature stop signal in the instructions for making all three versions of the alpha subunit, which disrupts the assembly of laminin 332. Without functional laminin 332, the epidermis is only weakly connected to the underlying layers of skin. Friction or other minor trauma (such as rubbing or scratching) can cause the skin layers to separate, leading to the formation of blisters. Infants with JEB generalized severe develop widespread blistering that causes life-threatening complications.

Other LAMA3 gene mutations cause the milder form of junctional epidermolysis bullosa, JEB generalized intermediate. Some of these mutations alter single protein building blocks (amino acids) in the alpha subunit of laminin 332. Others add or remove a small number of amino acids in the alpha subunit or change the way the gene's instructions are used to make the subunit. The genetic changes responsible for milder cases of junctional epidermolysis bullosa usually lead to the production of a laminin 332 protein that retains some of its function. Affected individuals experience blistering, but it may be limited to the hands, feet, knees, and elbows.

More About This Health Condition

Laryngo-onycho-cutaneous syndrome

At least three mutations in the LAMA3 gene have been found to cause laryngo-onycho-cutaneous (LOC) syndrome. This rare disorder is characterized by chronic skin sores (ulcers) and the widespread formation of red, bumpy patches called granulation tissue. A buildup of granulation tissue in different parts of the body can lead to serious complications, including vision loss and blockage of the airway. Other features of LOC syndrome include malformed nails and abnormal teeth.

The mutations involved in LOC syndrome lead to an abnormally short version of the alpha-3a subunit of laminin 332; alpha-3b1 and alpha-3b2 are normal. Laminin proteins containing the altered alpha subunit cannot effectively attach the epidermis to underlying layers of skin or regulate wound healing. These abnormalities of laminin 332 cause the chronic skin ulceration and overgrowth of granulation tissue that are characteristic of LOC syndrome. The inability of laminin 332 to perform its other functions leads to the nail and tooth abnormalities that occur in this condition.

LOC syndrome is typically considered a subtype of junctional epidermolysis bullosa (described above). Researchers suggest that LAMA3 gene mutations that affect only the alpha-3a version of the alpha subunit lead to LOC syndrome, while mutations that also affect the other versions of the alpha subunit lead to junctional epidermolysis bullosa.

More About This Health Condition

Other Names for This Gene

  • BM600
  • BM600 150kD subunit
  • BM600-150kDa
  • E170
  • epiligrin
  • epiligrin 170 kda subunit
  • epiligrin alpha 3 subunit
  • kalinin 165kD subunit
  • kalinin-165kDa
  • LAM5, alpha-3 subunit
  • LAMA3_HUMAN
  • lama3a
  • laminin 5, alpha-3 subunit
  • laminin A3
  • laminin alpha 3
  • laminin alpha 3 subunit
  • laminin, alpha 3
  • laminin, alpha-3
  • laminin-5 alpha 3 chain
  • LAMNA
  • LOCS
  • nicein 150kD subunit
  • nicein-150kDa

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P, Engel J, Engvall E, Hohenester E, Jones JC, Kleinman HK, Marinkovich MP, Martin GR, Mayer U, Meneguzzi G, Miner JH, Miyazaki K, Patarroyo M, Paulsson M, Quaranta V, Sanes JR, Sasaki T, Sekiguchi K, Sorokin LM, Talts JF, Tryggvason K, Uitto J, Virtanen I, von der Mark K, Wewer UM, Yamada Y, Yurchenco PD. A simplified laminin nomenclature. Matrix Biol. 2005 Aug;24(5):326-32. doi: 10.1016/j.matbio.2005.05.006. Citation on PubMed
  • Barzegar M, Mozafari N, Kariminejad A, Asadikani Z, Ozoemena L, McGrath JA. A new homozygous nonsense mutation in LAMA3A underlying laryngo-onycho-cutaneous syndrome. Br J Dermatol. 2013 Dec;169(6):1353-6. doi: 10.1111/bjd.12522. Citation on PubMed
  • Hamill KJ, McLean WH. The alpha-3 polypeptide chain of laminin 5: insight into wound healing responses from the study of genodermatoses. Clin Exp Dermatol. 2005 Jul;30(4):398-404. doi: 10.1111/j.1365-2230.2005.01842.x. Citation on PubMed
  • Hamill KJ, Paller AS, Jones JC. Adhesion and migration, the diverse functions of the laminin alpha3 subunit. Dermatol Clin. 2010 Jan;28(1):79-87. doi: 10.1016/j.det.2009.10.009. Citation on PubMed or Free article on PubMed Central
  • Hartwig B, Borm B, Schneider H, Arin MJ, Kirfel G, Herzog V. Laminin-5-deficient human keratinocytes: defective adhesion results in a saltatory and inefficient mode of migration. Exp Cell Res. 2007 May 1;313(8):1575-87. doi: 10.1016/j.yexcr.2007.02.003. Epub 2007 Feb 9. Citation on PubMed
  • Kim CC, Liang MG, Pfendner E, Kimonis VE. What syndrome is this? Laryngo-onycho-cutaneous syndrome. Pediatr Dermatol. 2007 May-Jun;24(3):306-8. doi: 10.1111/j.1525-1470.2007.00408.x. No abstract available. Citation on PubMed
  • McLean WH, Irvine AD, Hamill KJ, Whittock NV, Coleman-Campbell CM, Mellerio JE, Ashton GS, Dopping-Hepenstal PJ, Eady RA, Jamil T, Phillips R, Shabbir SG, Haroon TS, Khurshid K, Moore JE, Page B, Darling J, Atherton DJ, Van Steensel MA, Munro CS, Smith FJ, McGrath JA. An unusual N-terminal deletion of the laminin alpha3a isoform leads to the chronic granulation tissue disorder laryngo-onycho-cutaneous syndrome. Hum Mol Genet. 2003 Sep 15;12(18):2395-409. doi: 10.1093/hmg/ddg234. Epub 2003 Jul 15. Erratum In: Hum Mol Genet. 2004 Feb 1;13(3):365. Phillips Rodney J [corrected to Phillips Roderic J]. Citation on PubMed
  • Nakano A, Chao SC, Pulkkinen L, Murrell D, Bruckner-Tuderman L, Pfendner E, Uitto J. Laminin 5 mutations in junctional epidermolysis bullosa: molecular basis of Herlitz vs. non-Herlitz phenotypes. Hum Genet. 2002 Jan;110(1):41-51. doi: 10.1007/s00439-001-0630-1. Epub 2001 Nov 13. Citation on PubMed
  • Schneider H, Muhle C, Pacho F. Biological function of laminin-5 and pathogenic impact of its deficiency. Eur J Cell Biol. 2007 Dec;86(11-12):701-17. doi: 10.1016/j.ejcb.2006.07.004. Epub 2006 Sep 26. Citation on PubMed
  • Varki R, Sadowski S, Pfendner E, Uitto J. Epidermolysis bullosa. I. Molecular genetics of the junctional and hemidesmosomal variants. J Med Genet. 2006 Aug;43(8):641-52. doi: 10.1136/jmg.2005.039685. Epub 2006 Feb 10. Citation on PubMed or Free article on PubMed Central

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.