LAMC2 Gene

The LAMC2 gene (LAMC2 stands for Laminin Subunit Gamma 2) is a protein coding gene that is also located chromosome 1q25.3. Diseases associated with LAMC2 include:

• Epidermolysis bullosa junctionalis generalized severe (Herlitz type).
• Epidermolysis bullosa junctionalis generalized intermediate severe (Non-Herlitz type)
• Epidermolysis bullosa junctionalis localized (Non-Herlitz type)

Laminins, a family of extracellular matrix glycoproteins, are the major non-collagenous component of basement membranes. They are associated with a variety of biological processes, including cell adhesion, differentiation, migration, signal transduction, neurite growth, and metastasis.

Laminins are composed of three non-identical chains: laminin alpha, beta and gamma. They have a cruciform structure with three short arms, each formed by a different chain, and one long arm consisting of all three chains. Each laminin chain is a multidomain protein encoded by its own gene. Several isoforms of each chain have been described. The different isomers of the alpha, beta, and gamma chains combine to form different heterotrimeric laminin isoforms, which are designated by Arabic numerals in the order of their discovery, i.e., the heterotrimer alpha1beta1gamma1 is laminin 1.

The biological functions of the various chains and trimer molecules are largely unknown, but it has been shown that some of the chains differ in terms of their tissue distribution, presumably due to different functions in vivo. This gene encodes the isoform of the gamma chain of laminin, gamma 2.

The gamma 2 chain, previously thought to be a truncated version of the beta chain (B2t), is highly homologous to the gamma 1 chain; however, it lacks domain VI and domains V, IV, and III are shorter. It is expressed in several fetal tissues, but differently from gamma 1, and is specifically localized in epithelial cells in skin, lung, and kidney.

The gamma 2 chain, together with the alpha 3 and beta 3 chains, forms laminin 5 (historically named: calinin), which is an essential component of the anchoring filaments that connect epithelial cells to the underlying basement membrane. Epithelial-specific expression of gamma-2 chain suggests its role as an epithelial attachment molecule. Mutations in this gene are associated with epidermolysis bullosa junctionalis. Two transcript variants have been described that result from alternative splicing of the 3'-terminal exon and encode different isoforms of the gamma-2 chain. The two variants are differentially expressed in embryonic tissues, but the biological significance of the two forms is unknown.

Laminin, which binds to cells via a high-affinity receptor, is thought to mediate cell attachment, migration, and organization in tissues during embryonic development by interacting with other components of the extracellular matrix. Ladsin exerts a cell-scattering effect on a variety of cells, including epithelial, endothelial, and fibroblast cells.

1. Kon A et al. (1998) Laminin 5 genes and Herlitz junctional epidermolysis bullosa: novel mutations and polymorphisms in the LAMB3 and LAMC2 genes. Mutations in brief no. 190. online. Hum Mutat 12: 288.
2. Laimer M et al (2010) Herlitz junctional epidermolysis bullosa. Dermatol Clin 28:55-60.