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.

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 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.