On this page
LAMC2
laminin subunit gamma 2
The LAMC2 gene provides instructions for making the gamma 2 subunit of laminin 332, a critical protein involved in maintaining skin structure and integrity. The LAMC2 gene is responsible for producing a component of laminin 332, a protein vital for forming and maintaining basement membranes, particularly in the skin.
LAMC2 is located on the long (q) arm of chromosome 1, at band 1q25.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 1 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The LAMC2 gene encodes the laminin gamma 2 subunit, which is a key part of the laminin 332 protein (also known as laminin 5). Laminin 332 is a heterotrimeric protein, meaning it is composed of three distinct subunits (alpha, beta, and gamma) encoded by different genes. This protein is essential for the structural integrity and function of various tissues, with a prominent role in the skin.
What the gene does
Laminins are a family of proteins that regulate numerous cellular processes, including cell growth, motility, and adhesion. They are fundamental components of basement membranes, which are thin, sheet-like structures that provide support and separation between different cell layers in many tissues. Laminin 332, specifically, is highly expressed in the basement membrane underlying the epidermis, the outermost layer of the skin. Here, it contributes significantly to the skin's strength and resilience, acting as a barrier between the body and its external environment. Laminin 332 is a major constituent of anchoring filaments, which bridge the epidermal and dermal layers, effectively holding the skin together. Beyond its structural role, laminin 332 is also implicated in wound healing and may have functions in the cornea of the eye and the development of tooth enamel.
Video: Genetics 101
Chromosome location
The LAMC2 gene is located on chromosome 1 at position q25.3 (1q25.3). This chromosomal region contains the genetic instructions for the laminin gamma 2 subunit, influencing its expression and function within various tissues.
Protein structure
The LAMC2 gene encodes a protein that is 1193 amino acids in length. Its structure includes several important functional domains. These include multiple Laminin EGF-like domains: Laminin EGF-like 1 (amino acids 28-83), Laminin EGF-like 2 (amino acids 84-130), Laminin EGF-like 3 (amino acids 139-186), Laminin EGF-like 4 (first part: amino acids 187-196, second part: amino acids 382-415), Laminin EGF-like 5 (amino acids 416-461), Laminin EGF-like 6 (amino acids 462-516), Laminin EGF-like 7 (amino acids 517-572), and a truncated Laminin EGF-like 8 (amino acids 573-602). Additionally, the protein contains a Laminin IV type A domain (amino acids 213-381) and a large Domain II and I region (amino acids 603-1193), which includes three distinct coiled coil regions (amino acids 611-718, 811-1076, and 1117-1193).
Key variants
Variants within the LAMC2 gene can alter the production or function of the laminin gamma 2 subunit. These genetic changes can range from small alterations to larger deletions or insertions, impacting the protein's ability to participate in laminin 332 formation and its role in tissue integrity. Pathogenic variants can lead to inherited conditions, typically following an autosomal recessive inheritance pattern.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1045C>T | p.Arg349Ter | Pathogenic | ★★☆☆ | Junctional epidermolysis bullosa |
c.1350C>A | p.Tyr450Ter | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.136C>T | p.Gln46Ter | Pathogenic | ★★☆☆ | Epidermolysis bullosa, junctional 3B, severe |
c.1924G>T | p.Gly642Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Epidermolysis bullosa, junctional 3A, intermediate |
c.2074C>T | p.Gln692Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Junctional epidermolysis bullosa |
c.2489dup | p.Leu830fs | Pathogenic | ★★☆☆ | Junctional epidermolysis bullosa |
c.2881C>T | p.Gln961Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Junctional epidermolysis bullosa |
c.3365T>G | p.Leu1122Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Epidermolysis bullosa, junctional 3B, severe |
c.343C>T | p.Arg115Ter | Pathogenic | ★★☆☆ | Junctional epidermolysis bullosa gravis of Herlitz |
c.508C>T | p.Arg170Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Junctional epidermolysis bullosa |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the LAMC2 gene are primarily associated with Epidermolysis bullosa (junctional), an inherited skin disorder characterised by extreme skin fragility and blistering. The severity of the condition can vary, with more severe forms often resulting from variants that significantly impair or prevent the production of functional laminin 332. Such variants can lead to premature stop signals, disrupting the gene's instructions.
Inheritance pattern
Conditions caused by pathogenic LAMC2 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The LAMC2 gene is included in several UK NHS clinical genomic panels. It is listed as 'green' for Epidermolysis bullosa and also for Epidermolysis bullosa and congenital skin fragility (R164), indicating that there is strong evidence for its association with these conditions and that testing is routinely offered in the NHS for diagnostic purposes.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the LAMC2 gene?
The LAMC2 gene provides instructions for the gamma 2 subunit of laminin 332, a protein crucial for forming and maintaining basement membranes. This protein is essential for cell adhesion and movement, particularly in providing structural integrity and strength to the skin.
What condition is associated with variants in the LAMC2 gene?
Variants in the LAMC2 gene are primarily associated with Epidermolysis bullosa (junctional). This is an inherited skin disorder characterised by fragile skin that easily blisters due to impaired structural support at the dermal-epidermal junction.
How is Epidermolysis bullosa (junctional) inherited?
Epidermolysis bullosa (junctional) caused by LAMC2 variants typically follows an autosomal recessive inheritance pattern. This means an individual must inherit two copies of the altered gene (one from each parent) to develop the condition. Parents who each carry one altered copy are generally unaffected but have a 25% chance with each pregnancy of having an affected child.
References
- Schneider H, Mühle C, Pacho F. Biological function of laminin-5 and pathogenic impact of its deficiency. European journal of cell biology. 2007. PMID: 17000025
- Hartwig B, Borm B, Schneider H. Laminin-5-deficient human keratinocytes: defective adhesion results in a saltatory and inefficient mode of migration. Experimental cell research. 2007. PMID: 17335805
- Varki R, Sadowski S, Pfendner E. Epidermolysis bullosa. I. Molecular genetics of the junctional and hemidesmosomal variants. Journal of medical genetics. 2006. PMID: 16473856
- Mühle C, Jiang QJ, Charlesworth A. Novel and recurrent mutations in the laminin-5 genes causing lethal junctional epidermolysis bullosa: molecular basis and clinical course of Herlitz disease. Human genetics. 2005. PMID: 15538630
- Aumailley M, Bruckner-Tuderman L, Carter WG. A simplified laminin nomenclature. Matrix biology : journal of the International Society for Matrix Biology. 2005. PMID: 15979864
- Nakano A, Chao SC, Pulkkinen L. Laminin 5 mutations in junctional epidermolysis bullosa: molecular basis of Herlitz vs. non-Herlitz phenotypes. Human genetics. 2002. PMID: 11810295
- Castiglia D, Posteraro P, Spirito F. Novel mutations in the LAMC2 gene in non-Herlitz junctional epidermolysis bullosa: effects on laminin-5 assembly, secretion, and deposition. The Journal of investigative dermatology. 2001. PMID: 11564184
- Pulkkinen L, Uitto J. Mutation analysis and molecular genetics of epidermolysis bullosa. Matrix biology : journal of the International Society for Matrix Biology. 1999. PMID: 10367729