COL2A1
Encyclopedia
Collagen, type II, alpha 1 (primary osteoarthritis, spondyloepiphyseal dysplasia, congenital), also known as COL2A1, is a human
gene
that provides instructions for the production of the pro-alpha1(II) chain of type II collagen.
Type II collagen, which adds structure and strength to connective tissue
s, is found primarily in cartilage
, the jelly-like substance that fills the eyeball (the vitreous
), the inner ear
, and the center portion of the discs between the vertebrae in the spine
(nucleus pulposus). Three pro-alpha1(II) 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.
The COL2A1 gene is located on the long (q) arm of chromosome 12
between positions 13.11 and 13.2, from base pair
46,653,017 to base pair 46,684,527.
Human
Humans are the only living species in the Homo genus...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
that provides instructions for the production of the pro-alpha1(II) chain of type II collagen.
Type II collagen, which adds structure and strength to connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
s, is found primarily in cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
, the jelly-like substance that fills the eyeball (the vitreous
Vitreous humour
The vitreous humour or vitreous humor is the clear gel that fills the space between the lens and the retina of the eyeball of humans and other vertebrates...
), the inner ear
Inner ear
The inner ear is the innermost part of the vertebrate ear. In mammals, it consists of the bony labyrinth, a hollow cavity in the temporal bone of the skull with a system of passages comprising two main functional parts:...
, and the center portion of the discs between the vertebrae in the spine
Vertebral column
In human anatomy, the vertebral column is a column usually consisting of 24 articulating vertebrae, and 9 fused vertebrae in the sacrum and the coccyx. It is situated in the dorsal aspect of the torso, separated by intervertebral discs...
(nucleus pulposus). Three pro-alpha1(II) 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.
The COL2A1 gene is located on the long (q) arm of chromosome 12
Chromosome 12 (human)
Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 143 million base pairs and represents between 4 and 4.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic...
between positions 13.11 and 13.2, from base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
46,653,017 to base pair 46,684,527.
Related conditions
- Achondrogenesis type 2Achondrogenesis type 2Infants with achondrogenesis, type 2 have short arms and legs, a small chest with short ribs, and underdeveloped lungs. Achondrogenesis, type 2 is a subtype of collagenopathy, types II and XI. This condition is also associated with a lack of bone formation in the spine and pelvis...
: Several kinds of mutations in the COL2A1 gene are responsible for achondrogenesis, type 2. These mutations may include missing pieces of the COL2A1 gene, substitution of the amino acidAmino acidAmino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
building-block glycineGlycineGlycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
with another amino acid, or changes that cause important parts of the proteinProteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
to be left out. All of these mutations prevent the normal production of mature type II collagen, which results in achondrogenesis, type 2 by affecting tissues that are rich in type II collagen.
- Platyspondylic lethal skeletal dysplasia, Torrance typePlatyspondylic lethal skeletal dysplasia, Torrance typePlatyspondylic lethal skeletal dysplasia, Torrance type is a severe disorder of bone growth. People with this condition have very short arms and legs, a small chest with short ribs, underdeveloped pelvic bones, and unusually short fingers and toes...
:Fewer than 10 mutations in the COL2A1 gene have been identified in people with platyspondylic lethal skeletal dysplasia, Torrance type. Most of these mutations change a single protein building block (amino acid) in the pro-alpha1(II) chain. These COL2A1 mutations lead to the production of an abnormal version of the pro-alpha1(II) chain that cannot be incorporated into type II collagen fibers. As a result, cells make a reduced amount of type II collagen. Instead of forming collagen molecules, the abnormal pro-alpha1(II) chains build up in cartilage cells (chondrocytes). These changes disrupt normal bone development, resulting in skeletal abnormalities such as short arms and legs, a small chest, flattened vertebrae, and short fingers and toes.
- HypochondrogenesisHypochondrogenesisHypochondrogenesis is a severe genetic disorder causing malformations of bone growth. The condition is characterized by a short body and limbs and abnormal bone formation in the spine and pelvis....
: Several different types of mutations in the COL2A1 gene are responsible for hypochondrogenesis. These mutations may include missing pieces of the COL2A1 gene, the substitution of the building-block amino acid glycine with another amino acid, or changes that leave out important parts of the protein. All of these changes interfere with the formation of mature triple-stranded type II collagen molecules, which results in this type of hypochondrogenesis by affecting tissues that are rich in type II collagen.
- Kniest dysplasiaKniest dysplasiaKniest dysplasia is an uncommon inherited disorder of bone growth. The condition is characterized by dwarfism, enlarged joints, and other skeletal abnormalities, and problems with vision and hearing...
: Most of the mutations responsible for Kniest dysplasia cause abnormally short pro-alpha1(II) collagen chains to be produced in the cell. These short chains join with longer, normal-length collagen chains. The resulting abnormal type II collagen molecules are shorter than normal, causing the signs and symptoms of Kniest dysplasia.
- Spondyloepimetaphyseal dysplasia, Strudwick typeSpondyloepimetaphyseal dysplasia, Strudwick typeSpondyloepimetaphyseal dysplasia, Strudwick type is an inherited disorder of bone growth that results in dwarfism, characteristic skeletal abnormalities, and problems with vision. The name of the condition indicates that it affects the bones of the spine and two regions near the ends of bones...
: All of the mutations in the COL2A1 gene characterized to date cause an amino acid switch in the pro-alpha1(II) chain of type II collagen; specifically, the amino acid glycine is replaced by a different amino acid. The substitution of another amino acid for glycine in this chain inhibits the formation of stable, triple-stranded, ropelike collagen molecules. This results in spondyloepimetaphyseal dysplasia, Strudwick type by affecting tissues that are rich in type II collagen.
- Spondyloepiphyseal dysplasia congenitaSpondyloepiphyseal dysplasia congenitaSpondyloepiphyseal dysplasia congenita is a rare disorder of bone growth that results in dwarfism, characteristic skeletal abnormalities, and occasionally problems with vision and hearing...
: Spondyloepimetaphyseal dysplasia congenita can be caused by several types of mutations in the COL2A1 gene. These mutations may result in the incorrect substitution of an amino acid in the pro-alpha1(II) chain or the production of an abnormally short pro-alpha1(II) chain. All of these changes interfere with the formation of mature triple-stranded type II collagen molecules, which results in this type of spondyloepimetaphyseal dysplasia congenita by affecting tissues that are rich in type II collagen.
- Spondyloperipheral dysplasiaSpondyloperipheral dysplasiaSpondyloperipheral dysplasia is an autosomal dominant disorder of bone growth. The condition is characterized by flattened bones of the spine and unusually short fingers and toes . Some affected individuals also have other skeletal abnormalities, short stature, nearsightedness , hearing loss, and...
: Mutations that cause spondyloperipheral dysplasia lead to the production of an abnormally short pro-alpha1(II) chain that cannot be incorporated into type II collagen fibers. As a result, cells make a reduced amount of type II collagen. Instead of forming collagen molecules, the abnormal pro-alpha1(II) chains build up in cartilage cells (chondrocytes). These changes disrupt normal bone development, resulting in flattened vertebrae, short fingers and toes, and the other features of spondyloperipheral dysplasia.
- Stickler syndromeStickler syndromeStickler syndrome is a group of genetic disorders affecting connective tissue, specifically collagen. It was first studied and characterized by Gunnar B. Stickler in 1965. Stickler syndrome is a subtype of collagenopathy, types II and XI...
: Several of the mutations in the COL2A1 gene result in the production of an abnormally short protein that cannot be incorporated into a type II collagen fiber. Most of the mutations in COL2A1 that cause Stickler syndrome, however, have a premature stop signal in one copy of the gene. Because of this, cells produce only half of the normal amount of pro-alpha 1(II) collagen chains. This shortage results in underproduction of type II collagen in cartilage, causing the symptoms of Stickler syndrome, COL2A1.
- Other disorders with an increased risk from variations of the COL2A1 gene: Variations in the COL2A1 gene may increase the risk of developing osteoarthritis (OA), a degenerative disease of joint cartilage, in some people. The variations in this gene result in amino acid changes in the pro-alpha1(II) chain of type II collagen. These changes in the collagen fibers of the joints are thought to play a role in the wearing down of joint cartilage, resulting in the signs and symptoms of osteoarthritis.