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COL6A3 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

COL6A3 gene

The COL6A3 gene provides instructions for the alpha(α)3(VI) chain, a key component of type VI collagen that maintains the structural health of muscles and connective tissues.

Normal Function

The COL6A3 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 COL6A3 gene is the alpha(α)3(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 COL6A3 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 α3(VI) chain. The most frequently affected amino acid is glycine; changes to this building block disrupt the structure of the α3(VI) chain.

Variants in the COL6A3 gene affect type VI collagen in different ways:

  • Some variants lead to altered α3(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 α3(VI) chain, which impedes the formation of type VI collagen.

All of these COL6A3 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 α3(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 COL6A3 gene is found on chromosome 2.

Frequently Asked Questions

Surgical interventions must be evaluated with great caution. Tendon lengthening procedures often yield only temporary relief because contractures rapidly re-form, and the required postoperative immobilization can cause permanent muscle weakness and loss of walking ability. In contrast, surgical spinal stabilization for progressive scoliosis is frequently necessary and beneficial once curve progression begins to compromise lung capacity, provided that intraoperative and postoperative respiratory support is carefully managed.
Comprehensive management requires a multidisciplinary approach: pediatric pulmonology visits with spirometry and sleep studies every 6 to 12 months to detect nocturnal hypoventilation; orthopedic monitoring to screen for rapidly progressive scoliosis, hip dysplasia, and limb contractures; regular physical and occupational therapy evaluations to adapt mobility aids and splints; and nutritional monitoring, as poor weight gain and feeding fatigue can occur due to weak chewing muscles.
Dominant-negative mutations occur when an altered alpha-3(VI) chain is incorporated into the triple-helix collagen molecule, disrupting the entire structure even if normal chains are present; these typically cause moderate to severe disease, such as classic Ullrich congenital muscular dystrophy or pronounced Bethlem myopathy. In contrast, recessive mutations (such as nonsense or frameshift changes causing total loss of the protein from one allele) require two mutated copies to cause disease; depending on whether any functional collagen VI is produced, recessive cases can range from severe congenital presentations to mild, late-onset muscular weakness.
Yes. In individuals with COL6A3 mutations, muscle fibers lack the normal protective structural cushion provided by type VI collagen in the extracellular matrix, making them highly vulnerable to mechanical stress. High-intensity resistance training, sprinting, or heavy eccentric exercises (such as running downhill or heavy weight lifting) can cause cellular microtrauma and accelerate muscle fiber loss. Safe exercise focuses on gentle stretching, stationary cycling, walking, and warm-water pool therapy.
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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