COL9A1

The COL9A1 gene provides instructions for making part of a large molecule called type IX collagen. Collagens are a family of proteins that strengthen and support connective tissues, such as skin, bone, cartilage, tendons, and ligaments. In particular, type IX collagen is an important component of cartilage.

Type IX collagen is made up of three proteins that are produced from three distinct genes: one α1(IX) chain, which is produced from the COL9A1 gene, one α2(IX) chain, which is produced from the COL9A2 gene, and one α3(IX) chain, which is produced from the COL9A3 gene. Type IX collagen is more flexible than other types of collagen molecules and is closely associated with type II collagen. Researchers believe that the flexible nature of type IX collagen allows it to act as a bridge that connects type II collagen with other cartilage components. Studies have shown that type IX collagen also interacts with the proteins produced from the MATN3 and COMP genes.

multiple epiphyseal dysplasia - caused by mutations in the COL9A1 gene

At least one mutation in the COL9A1 gene has been found to cause dominant multiple epiphyseal dysplasia. This particular mutation, called a splice-site mutation, involves the addition of one DNA building block (nucleotide) near an area of the gene called exon 8 (written as 1-bp ins, IVS8, T, +3). This mutation disrupts the way the gene's instructions are used to make the α1(IX) chain, resulting in a deletion of several protein building blocks (amino acids). It is not known how this mutation in COL9A1 causes the signs and symptoms of dominant multiple epiphyseal dysplasia.

All identified mutations in type IX collagen delete a portion of the COL3 domain, which suggests that this region has an important function. Mutations may affect the ability of type IX collagen to fold correctly or interact with other cartilage components.

Stickler syndrome - caused by mutations in the COL9A1 gene

Researchers have identified one family in Morocco with Stickler syndrome caused by a mutation in the COL9A1 gene. This mutation (written as Arg295Ter or R295X) occurs in both copies of the COL9A1 gene in each cell and results in a premature stop signal in the instructions for making type IX collagen. Researchers believe that the R295X mutation causes the production of an abnormally short, nonfunctional version of type IX collagen. This lack of type IX collagen results in the signs and symptoms of Stickler syndrome, including overly flexible joints, distinctive facial features, hearing loss, and severe nearsightedness with associated eye problems.