LAMC2 gene
laminin subunit gamma 2
The LAMC2 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 LAMC2 gene carries instructions for the gamma subunit; the alpha and beta subunits are produced from other genes.
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 for wound healing. 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.
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More than 40 mutations in the LAMC2 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 the gamma subunit of laminin 332, which prevents the assembly of this protein. Without 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 LAMC2 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 gamma subunit of laminin 332. Others add or remove a small number of amino acids in the gamma subunit or change the way the gene's instructions are used to make the subunit. The genetic changes responsible for JEB generalized intermediate 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 and often improves after the newborn period.
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Cytogenetic Location: 1q25.3, which is the long (q) arm of chromosome 1 at position 25.3
Molecular Location: base pairs 183,186,264 to 183,245,127 on chromosome 1 (Homo sapiens Updated Annotation Release 109.20191205, GRCh38.p13) (NCBI)
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- B2T
- BM600
- BM600-100kDa
- cell-scattering factor (140kDa)
- CSF
- EBR2
- EBR2A
- kalinin (105kD)
- kalinin-105kDa
- ladsin (140kDa)
- LAM5, gamma-2 subunit
- LAMB2T
- LAMC2_HUMAN
- laminin 5, gamma-2 subunit
- laminin, gamma 2
- laminin, gamma-2
- laminin, nicein, beta-2
- LAMNB2
- MGC138491
- MGC141938
- nicein (100kDa)
- nicein-100kDa
Related Information
- 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. Review.
- Castiglia D, Posteraro P, Spirito F, Pinola M, Angelo C, Puddu P, Meneguzzi G, Zambruno G. Novel mutations in the LAMC2 gene in non-Herlitz junctional epidermolysis bullosa: effects on laminin-5 assembly, secretion, and deposition. J Invest Dermatol. 2001 Sep;117(3):731-9.
- 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. Epub 2007 Feb 9.
- Mühle C, Jiang QJ, Charlesworth A, Bruckner-Tuderman L, Meneguzzi G, Schneider H. Novel and recurrent mutations in the laminin-5 genes causing lethal junctional epidermolysis bullosa: molecular basis and clinical course of Herlitz disease. Hum Genet. 2005 Jan;116(1-2):33-42. Epub 2004 Nov 5.
- 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. Epub 2001 Nov 13.
- Pulkkinen L, Uitto J. Mutation analysis and molecular genetics of epidermolysis bullosa. Matrix Biol. 1999 Feb;18(1):29-42. Review.
- Schneider H, Mühle 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. Epub 2006 Sep 26.
- 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. Epub 2006 Feb 10.