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COL6A2 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

COL6A2 gene

The COL6A2 gene encodes the alpha(α)2(VI) chain, a critical building block of type VI collagen that supports the stability of skeletal muscles and connective tissues.

Normal Function

The COL6A2 gene provides instructions for making one component of type VI collagen, which is a flexible protein found in the space that surrounds cells. Specifically, the protein produced from the COL6A2 gene is the alpha(α)2(VI) chain of type VI collagen. This chain combines with chains produced from other genes to produce a complete type VI collagen molecule.

Collagens are found in the extracellular matrix, which is an intricate lattice that forms in the space between cells and provides structural support. Type VI collagen is located in the extracellular matrix surrounding cells that make up the muscles used for movement (skeletal muscle cells) and cells that make up connective tissue, which provides strength and flexibility to structures throughout the body, including skin and joints. The extracellular matrix is necessary for cell stability and growth. Research suggests that type VI collagen links basement membranes, which are thin, sheet-like structures that are part of the extracellular matrix, to nearby cells.

Health Conditions Related to Genetic Changes

Collagen VI-related dystrophy

Variants (also known as mutations) in the COL6A2 gene have been found to cause some cases of collagen VI-related dystrophy, which is a group of disorders that vary in severity but generally result in muscle weakness and joint deformities called contractures. These variants often change single protein building blocks (amino acids) in the α2(VI) chain. The most frequently affected amino acid is glycine; changes to this building block disrupt the structure of the α2(VI) chain.

Variants in the COL6A2 gene affect type VI collagen in different ways:

  • Some variants lead to altered α2(VI) chains that can be incorporated into the mature type VI collagen molecule, although they disrupt the molecule's structure and function.
  • Other variants result in an altered chain that cannot be incorporated at all.
  • Some variants prevent the production of any functional α2(VI) chain, which impedes the formation of type VI collagen.

All of these COL6A2 gene variants lead to a reduction or absence of functional collagen VI molecules. While it is difficult to predict the severity of collagen VI-related dystrophy based on the type of variant, in general, lower amounts of type VI collagen lead to more severe signs and symptoms that begin earlier in life.

Changes in α2(VI) chain structure or production lead to an unstable extracellular matrix that is no longer attached to cells through the basement membrane. As a result, the stability of muscle cells and connective tissue progressively declines, which leads to the muscle weakness, contractures, and other signs and symptoms of collagen VI-related dystrophy.

Limb-girdle muscular dystrophy

MedlinePlus Genetics provides information about Limb-girdle muscular dystrophy.

Genomic Location

The COL6A2 gene is found on chromosome 21.

Frequently Asked Questions

This coexistence of contractures and hypermobility is a hallmark clinical clue for collagen VI disorders. Because type VI collagen is essential for both muscle structure and tendon flexibility, its defect creates contradictory symptoms: large, proximal joints such as the elbows, hips, and knees tend to develop rigid, progressive contractures (shortening and tightness), while small, distal joints such as the fingers, wrists, and ankles exhibit striking hyperlaxity (hyperextensibility).
Patients with COL6A2 variants require specialized anesthesia care. Jaw stiffness and neck contractures can make endotracheal intubation difficult, requiring advanced airway equipment like video laryngoscopy or fiberoptic tools. Furthermore, underlying diaphragmatic weakness increases the risk of post-extubation respiratory failure, necessitating pre-planned non-invasive ventilation. Depolarizing muscle relaxants such as succinylcholine are generally avoided due to theoretical risks of rhabdomyolysis or severe hyperkalemia in muscular dystrophies.
Because the alpha-2(VI) chain is a major structural protein in the extracellular matrix of the dermis, COL6A2 variants frequently cause cutaneous abnormalities. Common features include keratosis pilaris (rough, follicular bumps on the arms and thighs), abnormal wound healing, the formation of keloids or hypertrophic scars after minor injuries or surgical incisions, and thin, crinkly skin resembling cigarette paper over the palms and soles.
When genetic sequencing identifies a COL6A2 variant of uncertain significance (VUS), clinicians often perform a skin biopsy to culture dermal fibroblasts. Immunohistochemical staining and Western blotting are then used to evaluate whether collagen VI is properly secreted and assembled into the extracellular matrix. Additionally, muscle MRI often reveals a characteristic pattern of fatty infiltration with a rim of peripheral preservation in specific thigh muscles (such as the rectus femoris), helping confirm a functional deficit.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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