COL9A3

The COL9A3 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 COL9A3 gene

At least three mutations in the COL9A3 gene have been shown to cause dominant multiple epiphyseal dysplasia. All of these mutations disrupt how genetic information is spliced together to make the blueprint for producing the α3(IX) chain. These mutations, called splice-site mutations, change one DNA building block (nucleotide) near an area of the gene called exon 3. These mutations in the COL9A3 gene result in the deletion of 12 protein building blocks (amino acids) from the α3(IX) chain. It is not known how mutations in COL9A3 cause 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.

other disorders - increased risk from variations of the COL9A3 gene

At least one mutation in the COL9A3 gene increases an individual's risk for intervertebral disc disease, one of the most common sources of lower back pain. This mutation substitutes the amino acid tryptophan for the amino acid arginine at position 103 in the α3(IX) chain. The mutation is commonly known as the Trp3 allele and is sometimes written as p.Arg103Trp. A person with at least one Trp3 allele has three times the risk of developing intervertebral disc disease compared with someone without the Trp3 allele. The amino acid tryptophan is rarely found in collagen molecules, and it likely alters the structure or function of type IX collagen.