COL6A3

The COL6A3 gene provides instructions for making one component of type VI collagen, which is a flexible protein that surrounds muscle cells. Specifically, the protein produced from the COL6A3 gene is the alpha(α)3(VI) chain of type VI collagen. This chain combines with two other types of α(VI) chains (the α1 and α2 chains) to make a molecule called a collagen VI monomer. Two collagen VI monomers attach (bind) together to form collagen VI dimers. Two dimers group together to form a larger molecule called a tetramer, which is the complete type VI collagen molecule.

Type VI collagen molecules form complex networks that make up a large portion of the extracellular matrix surrounding muscle cells. The extracellular matrix is an intricate lattice that forms in the space between cells and provides structural support. The extracellular matrix that surrounds muscle cells is necessary for muscle cell stability and growth. Type VI collagen networks play an especially important role in the extracellular matrix of muscle that is used for movement (skeletal muscle).

Bethlem myopathy - caused by mutations in the COL6A3 gene

At least 10 mutations in the COL6A3 gene have been found to cause Bethlem myopathy. Most of these mutations change single protein building blocks (amino acids) in the α3(VI) chain, which alters its structure. If the abnormal chain is not incorporated into type VI collagen, but is instead broken down soon after it is made, then not enough α3(VI) chain is available for the formation of type VI collagen. The loss of this chain leads to decreased amounts of this type of collagen.

In people with Bethlem myopathy, some normal type VI collagen is produced, but not enough to form a strong extracellular matrix. Over time, a deficient extracellular matrix leads to muscle weakness and the other signs and symptoms of Bethlem myopathy. Mutations in the COL6A3 gene are responsible for approximately 15 percent of all cases of Bethlem myopathy.

Ullrich congenital muscular dystrophy - caused by mutations in the COL6A3 gene

At least 10 mutations in the COL6A3 gene have been found to cause Ullrich congenital muscular dystrophy. Some of these mutations change single amino acids and some disrupt the way the gene's instructions are used to make the α3(VI) chain. These mutations result in an absence or severe deficiency of type VI collagen. A lack of type VI collagen disrupts the extracellular matrix surrounding muscle cells, leading to muscle weakness and the other signs and symptoms of Ullrich congenital muscular dystrophy.