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LAMA3

laminin subunit alpha 3

The LAMA3 gene provides instructions for a key subunit of laminin 332, a protein essential for maintaining the structural integrity of the skin's basement membrane. LAMA3 plays a critical role in forming laminin 332, a protein that supports cell adhesion and tissue structure, particularly in the skin.

Chromosome 18q11.2 Autosomal recessive HGNC:6483 Tier C
LAMA3 18q11.2 p arm q arm 18

LAMA3 is located on the long (q) arm of chromosome 18, at band 18q11.2. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 18 in the library →

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Clinical tests that include this

Carrier Screening panel
LAMA3 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The LAMA3 gene contains the genetic blueprint for one part of the laminin 332 protein, specifically the alpha-3 subunit. This laminin is a crucial component of basement membranes, which are thin, supportive layers found in many tissues throughout the body, including the skin. Proper functioning of LAMA3 is vital for maintaining the strength and resilience of the skin.

What the gene does

LAMA3 provides instructions for the alpha subunit of laminin 332, a trimeric protein vital for regulating cell growth, movement, and adhesion. Laminin 332 is a major constituent of the basement membrane, the supportive structure beneath the epidermis, providing strength and acting as a barrier. It is particularly important in anchoring filaments, which connect skin layers and enhance skin cohesion. Beyond its role in structural support, laminin 332 is also involved in early wound healing processes. Other laminins, such as laminin 311 and 321, also incorporate the alpha subunit from LAMA3 and contribute to skin strength, with laminin 311 additionally implicated in cell signalling in various tissues like the lungs. The LAMA3 gene can produce different versions of its alpha subunit, specifically alpha-3a, alpha-3b1, and alpha-3b2.

Video: Genetics 101

Chromosome location

The LAMA3 gene is situated on chromosome 18, specifically at position 18q11.2. This location refers to the long (q) arm of chromosome 18, within band 11.2.

Protein structure

The LAMA3 gene encodes a protein that is 3333 amino acids long, featuring several important domains. These include a Laminin N-terminal Domain (amino acids 43-298), followed by Domain V (amino acids 298-728). Within Domain V, there are several Laminin EGF-like domains: Laminin EGF-like 1 (amino acids 299-355), Laminin EGF-like 2 (amino acids 356-425), Laminin EGF-like 3 (amino acids 426-469), Laminin EGF-like 4 (amino acids 491-535), Laminin EGF-like 5 (amino acids 536-588), Laminin EGF-like 6 (amino acids 590-630), Laminin EGF-like 7 (amino acids 631-683), and Laminin EGF-like 8 (amino acids 684-728). Further downstream is Domain IV 1 (domain IV B) (amino acids 796-1265), and Domain III B (amino acids 1266-1465), which contains Laminin EGF-like 9 (amino acids 1266-1311), Laminin EGF-like 10 (amino acids 1312-1355), and Laminin EGF-like 11 (amino acids 1356-1404).

Domain map · 3,333 amino acids
Laminin N-terminal (43–298)Laminin EGF-like 2 (356–425)Laminin IV type A (1476–1653)Laminin G-like 1 (2390–2591)Laminin G-like 2 (2598–2760)Laminin G-like 3 (2767–2927)Laminin G-like 4 (2986–3150)Laminin G-like 5 (3157–3330)Laminin N-terminal43–298Laminin IV type A1476–1653Laminin G-like 12390–25911~1,6673,333
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:Q16787Length:3,333 aaStructure:AlphaFold

Key variants

Genetic variations within the LAMA3 gene can alter the production or function of the laminin 332 alpha-3 subunit. These changes may lead to a non-functional protein or affect its ability to properly assemble into laminin 332. Variants are typically inherited in an autosomal recessive pattern, meaning an individual must inherit two altered copies of the gene, one from each parent, to develop a condition.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for LAMA3.
View all on ClinVar →

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.1273+51C>T
single nucleotide variant
 R442* Pathogenic/Likely pathogenic ★★☆☆ Laryngo-onycho-cutaneous syndrome
c.5061C>A
single nucleotide variant
 p.Cys1687Ter Pathogenic/Likely pathogenic ★★☆☆ not provided
c.5119C>T
single nucleotide variant
 p.Gln1707Ter Pathogenic ★★☆☆ Epidermolysis bullosa, junctional 2B, severe
c.7120C>T
single nucleotide variant
 p.Arg2374Ter Pathogenic ★★☆☆ not provided
c.8043G>A
single nucleotide variant
 p.Ser2681= Pathogenic/Likely pathogenic ★★☆☆ Laryngo-onycho-cutaneous syndrome
c.8211C>A
single nucleotide variant
 p.Cys2737Ter Pathogenic/Likely pathogenic ★★☆☆ Epidermolysis bullosa, junctional 2B, severe
c.8420T>G
single nucleotide variant
 p.Leu2807Ter Pathogenic/Likely pathogenic ★★☆☆ Epidermolysis bullosa, junctional 2A, intermediate
c.8705del
Deletion
 p.Gln2902fs Pathogenic/Likely pathogenic ★★☆☆ Epidermolysis bullosa, junctional 2A, intermediate
c.8755A>T
single nucleotide variant
 p.Lys2919Ter Pathogenic ★★☆☆ Junctional epidermolysis bullosa
c.9642G>T
single nucleotide variant
 p.Lys3214Asn 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 LAMA3 gene are primarily associated with inherited skin disorders, most notably Epidermolysis bullosa (junctional). This group of conditions is characterised by extreme skin fragility and blistering due to issues with skin adhesion. Laryngo-onycho-cutaneous syndrome is another rare condition linked to LAMA3 variants, presenting with chronic skin ulcers and excessive granulation tissue formation.

Inheritance pattern

Conditions caused by pathogenic LAMA3 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous LAMA3 carrier status across ancestry groups?

UK clinical status

The LAMA3 gene is recognised in the UK National Health Service (NHS) Genomic Medicine Service. It is included on PanelApp for conditions such as Epidermolysis bullosa and Amelogenesis imperfecta, indicating its relevance in clinical genetic testing for these specific disorders.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Amelogenesis imperfecta · R340 NHS GMS → Epidermolysis bullosa and congenital skin fragility · R164 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main role of the LAMA3 gene?

The LAMA3 gene provides instructions for creating a subunit of laminin 332, a protein vital for the structural integrity and adhesion of skin layers, particularly in the basement membrane beneath the epidermis.

What happens if there are variants in the LAMA3 gene?

Variants in the LAMA3 gene can lead to conditions where the laminin 332 protein is not produced correctly or effectively. This can result in fragile skin and blistering, as seen in conditions like Epidermolysis bullosa (junctional).

How are conditions related to LAMA3 typically inherited?

Conditions associated with LAMA3 gene variants, such as Epidermolysis bullosa (junctional), are typically inherited in an autosomal recessive pattern. This means an individual must inherit a pathogenic variant from each parent to be affected.

References

  1. Barzegar M, Mozafari N, Kariminejad A. A new homozygous nonsense mutation in LAMA3A underlying laryngo-onycho-cutaneous syndrome. The British journal of dermatology. 2013. PMID: 23869449
  2. Hamill KJ, Paller AS, Jones JC. Adhesion and migration, the diverse functions of the laminin alpha3 subunit. Dermatologic clinics. 2010. PMID: 19945619
  3. 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
  4. 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
  5. Kim CC, Liang MG, Pfendner E. What syndrome is this? Laryngo-onycho-cutaneous syndrome. Pediatric dermatology. 2007. PMID: 17542886
  6. Varki R, Sadowski S, Pfendner E. Epidermolysis bullosa. I. Molecular genetics of the junctional and hemidesmosomal variants. Journal of medical genetics. 2006. PMID: 16473856
  7. Hamill KJ, McLean WH. The alpha-3 polypeptide chain of laminin 5: insight into wound healing responses from the study of genodermatoses. Clinical and experimental dermatology. 2005. PMID: 15953081
  8. Aumailley M, Bruckner-Tuderman L, Carter WG. A simplified laminin nomenclature. Matrix biology : journal of the International Society for Matrix Biology. 2005. PMID: 15979864
  9. McLean WH, Irvine AD, Hamill KJ. An unusual N-terminal deletion of the laminin alpha3a isoform leads to the chronic granulation tissue disorder laryngo-onycho-cutaneous syndrome. Human molecular genetics. 2003. PMID: 12915477
  10. 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
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 30 August 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .