Collagen, type II, alpha 1
Collagen, type II, alpha 1 , also known as COL2A1, is a human gene that provides instructions for the production of the pro-alpha1 chain of type II collagen.
Gene
The COL2A1 gene is located on the long arm of chromosome 12 between positions 13.11 and 13.2, from base pair 46,653,017 to base pair 46,684,527. The expression of COL2A1 is regulated by SOX-9 and retrotransposon gag-like-3 gene RTL3 in chondrocytes.There are two transcripts identified for this gene.
Function
This gene encodes the alpha-1 chain of type II collagen, a fibrillar collagen found in cartilage and the vitreous humor of the eye.Type II collagen, which adds structure and strength to connective tissues, is found primarily in cartilage, the jelly-like substance that fills the eyeball, the inner ear, and the center portion of the discs between the vertebrae in the spine. Three pro-alpha1 chains twist together to form a triple-stranded, ropelike procollagen molecule. These procollagen molecules must be processed by enzymes in the cell. Once these molecules are processed, they leave the cell and arrange themselves into long, thin fibrils that cross-link to one another in the spaces around cells. The cross-linkages result in the formation of very strong mature type II collagen fibers.
Clinical significance
Mutations in the COL2A1 gene are associated with achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome, and spondyloepimetaphyseal dysplasia Strudwick type. In addition, defects in processing chondrocalcin, a calcium binding protein that is the C-propeptide of this collagen molecule, are also associated with chondrodysplasia.Achondrogenesis type 2
Several kinds of mutations in the COL2A1 gene are responsible for Achondrogenesis type 2. These include missing pieces of the gene, substitution of the amino acid glycine with another amino acid, or changes that result in truncated proteins. All these mutations disrupt the production of mature type II collagen, affecting tissues rich in this collagen.Platyspondylic lethal skeletal dysplasia, Torrance type
Fewer than 10 COL2A1 mutations have been identified in people with Platyspondylic lethal [skeletal dysplasia, Torrance type]. Most result in a single amino acid change in the pro-alpha1 chain, producing an abnormal chain that cannot be incorporated into collagen fibers. This leads to reduced collagen production and skeletal abnormalities such as short limbs, small chest, flattened vertebrae, and short fingers and toes.Hypochondrogenesis
Hypochondrogenesis is caused by various COL2A1 mutations, including deletions, glycine substitutions, and truncations. These interfere with the formation of mature, triple-stranded type II collagen molecules, affecting collagen-rich tissues.Kniest dysplasia
Most mutations responsible for Kniest dysplasia result in abnormally short pro-alpha1 collagen chains that combine with normal-length chains, producing shorter-than-normal collagen molecules. This results in the characteristic features of Kniest dysplasia.Spondyloepimetaphyseal dysplasia
All known COL2A1 mutations in Spondyloepimetaphyseal dysplasia, Strudwick type replace glycine with another amino acid in the pro-alpha1 chain, disrupting the formation of stable, triple-stranded collagen molecules.Spondyloepiphyseal dysplasia congenita is caused by several types of COL2A1 mutations, including incorrect amino acid substitutions and truncated pro-alpha1 chains, impairing the formation of mature collagen molecules.
In Spondyloperipheral dysplasia, COL2A1 mutations produce a truncated pro-alpha1 chain that cannot be incorporated into collagen fibers. The abnormal chains accumulate in cartilage cells, disrupting bone development and resulting in flattened vertebrae and short digits.