COL2A1 gene
The COL2A1 gene provides instructions for making type II collagen, a protein essential for the development and strength of joints, eyes, and the inner ear.
Normal Function
The COL2A1 gene provides instructions for making the basic component of type II collagen, called the alpha-1(II) chain. Type II collagen adds structure and strength to connective tissues and plays an important role in the normal development of joints, eyes, and the inner ear.
Type II collagen is found primarily in cartilage, a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later replaced by bone, except for the cartilage that covers and protects the ends of bones and the cartilage that is present in the nose and external ears. Type II collagen is particularly abundant in a form of cartilage known as hyaline cartilage, which is found in the developing skeleton, joints, and at the end of the long bones of the arms and legs where new bone is produced (growth plates). Type II collagen is also part of the inner ear, the clear gel that fills the eyeball (the vitreous), and the center portion (nucleus pulposus) of the discs between the bones of the spine (vertebrae).
To construct type II collagen, three alpha-1(II) chains twist together to form a procollagen molecule. Procollagen molecules are then processed by enzymes in the cell. Once processed, the modified collagen molecules leave the cell and arrange themselves into long, thin fibrils that attach (bind) to one another in a lattice pattern (cross-link) in the spaces around cells. The cross-linkages result in the formation of very strong, mature type II collagen fibers.
Health Conditions Related to Genetic Changes
Achondrogenesis
Several variants in the COL2A1 gene have been found to cause hypochondrogenesis and a form of achondrogenesis called achondrogenesis type 2. These disorders are characterized by short bones in the arms and legs, a small chest with underdeveloped lungs (lung hypoplasia), and a lack of normal bone formation (ossification) in the spine. Affected individuals typically die before birth or shortly thereafter.
Kniest dysplasia
Multiple variants in the COL2A1 gene have been found in individuals with Kniest dysplasia. This condition is a skeletal disorder characterized by short stature, short arms and legs, progressive curvature of the spine, joint disease, and problems with vision and hearing. These variants lead to the production of abnormal alpha-1(II) chains, resulting in an abnormal version of type II collagen that cannot function properly.
Platyspondylic dysplasia, Torrance type
Multiple variants in the COL2A1 gene have been identified in individuals with platyspondylic dysplasia, Torrance type. This severe disorder of bone growth is characterized by very short arms and legs, a small chest with short ribs, unusually short fingers and toes (brachydactyly), and flattened vertebrae (platyspondyly). Affected individuals often die before birth or shortly thereafter.
Spondyloepiphyseal dysplasia with marked metaphyseal changes
Variants in the COL2A1 gene have been found to cause spondyloepiphyseal dysplasia (SED) with marked metaphyseal changes, a group of rare skeletal disorders that affect the vertebrae and the long bones in the arms and legs. These variants disrupt the formation of stable collagen molecules, preventing bones and other connective tissues from developing properly.
Spondyloepiphyseal dysplasia congenita
Several variants in the COL2A1 gene have been found to cause spondyloepiphyseal dysplasia (SED) congenita, a disorder of bone development that causes short stature with short arms and legs and a particularly short torso. People with SED congenita also have problems with vision and hearing.
Spondyloepiphyseal dysplasia with metatarsal shortening
A specific COL2A1 gene variant causes spondyloepiphyseal dysplasia (SED) with metatarsal shortening, a condition that affects joint function and bone development. Affected individuals are typically of average height and have joint pain that begins in childhood or adolescence. Many people with this condition have short toes.
Spondyloperipheral dysplasia
Variants in the COL2A1 gene have been found to cause spondyloperipheral dysplasia. This disorder of bone growth is characterized by disproportionate short stature, brachydactyly, platyspondyly, and other skeletal abnormalities.
Stickler syndrome
Variants in the COL2A1 gene are the most common cause of Stickler syndrome. People with this condition are typically of average height and have a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. Variants can also cause a form of Stickler syndrome that primarily affects the eyes, including severe nearsightedness (high myopia) and retinal detachment.
Other disorders
Variants in the COL2A1 gene have been associated with a group of milder conditions called dysplasia of the proximal femoral epiphyses that are characterized by normal stature and joint problems.
Other Names for This Gene
- collagen of cartilage
- collagen, type II
- collagen, type II, alpha 1
- collagen, type II, alpha 1 (primary osteoarthritis, spondyloepiphyseal dysplasia, congenital)