Normal Function
The COL11A1 gene provides instructions for making a component of type XI collagen called the pro-alpha1(XI) chain. Collagens are molecules that provide structure and strength to the connective tissues that support the body's muscles, joints, organs, and skin. Type XI collagen is normally found in cartilage, a tough but flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type XI collagen is also part of the inner ear; the vitreous, which is the clear gel that fills the eyeball; and the nucleus pulposus, which is the center portion of the discs between the bones of the spine (vertebrae).
Collagens begin as rope-like procollagen molecules that are each made up of three chains. The pro-alpha1(XI) chain combines with two other collagen chains, pro-alpha2(XI) and pro-alpha1(II), to form a triple-stranded procollagen molecule. Then the ropelike procollagen is processed by enzymes to create mature collagen. Mature collagen molecules arrange themselves into long, thin fibrils that form stable interactions (cross-links) with one another in the spaces between cells (the extracellular matrix). The cross-links result in the formation of very strong type XI collagen fibers.
Type XI collagen also helps maintain the spacing and width (diameter) of another type of collagen molecule, type II collagen. Type II collagen is an important component of the vitreous and cartilage. The arrangement and size of type II collagen fibrils is essential for the normal structure of these tissues.
Health Conditions Related to Genetic Changes
Fibrochondrogenesis
At least seven variants in the COL11A1 gene have been identified in people with fibrochondrogenesis type 1, a disorder of bone growth characterized by severe skeletal abnormalities, hearing loss, and vision loss. Infants with fibrochondrogenesis type 1 have a very narrow chest that prevents the lungs from developing normally. Most children with this condition are stillborn or die shortly after birth from respiratory failure, although some have lived into childhood.
Some cases of fibrochondrogenesis type 1 result from a combination of COL11A1 gene variants. Specifically, one copy of the gene has a variant that prevents the production of any functional pro-alpha1(XI) chain, and the other copy has a variant that results in an abnormal version of the pro-alpha1(XI) chain. When the abnormal chain is incorporated into collagen molecules, it creates defective type XI collagen. The abnormal collagen weakens connective tissues, impairing the formation of bones throughout the skeleton and causing changes in the eye and inner ear that lead to vision and hearing problems.
In at least two reported cases, fibrochondrogenesis type 1 has been caused by combinations of COL11A1 gene variants that completely eliminate the production of the pro-alpha1(XI) chain. Researchers speculate that a loss of this chain changes the structure of type XI collagen molecules and disrupts its ability to form cross-links. However, the effects of these variants are still under study.
More About This Health ConditionStickler syndrome
Variants in the COL11A1 gene account for 10 to 20 percent of all cases of Stickler syndrome. Signs and symptoms of this condition include a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms tend to be less severe than those of fibrochondrogenesis (described above). However, they vary widely among affected individuals.
More than two dozen COL11A1 gene variants have been found in people with Stickler syndrome. Some of these variants change single protein building blocks (amino acids) or delete a small number of amino acids from the pro-alpha1(XI) chain. Other variants cause segments of DNA to be skipped when the protein is made, resulting in an abnormally short pro-alpha1(XI) chain. All of these changes impair the production or assembly of type XI collagen molecules. Defective collagen disrupts the normal development of connective tissues in many different parts of the body, which leads to the varied signs and symptoms of Stickler syndrome.
More About This Health ConditionCarpal tunnel syndrome
MedlinePlus Genetics provides information about Carpal tunnel syndrome
More About This Health ConditionIntervertebral disc disease
MedlinePlus Genetics provides information about Intervertebral disc disease
More About This Health ConditionOsteoarthritis
MedlinePlus Genetics provides information about Osteoarthritis
More About This Health ConditionOther disorders
Variants in the COL11A1 gene can also cause Marshall syndrome, a condition that is very similar to Stickler syndrome. Some researchers have classified Marshall syndrome as a variant of Stickler syndrome, while others consider it to be a separate disorder. Most of the variants associated with Marshall syndrome cause a segment of DNA in the COL11A1 gene to be skipped when the protein is made, resulting in an abnormally short pro-alpha1(XI) chain. This shortened protein impairs the formation of mature type XI collagen, which leads to the abnormal development of connective tissues and the signs and symptoms of Marshall syndrome.
Other Names for This Gene
- COLL6
- collagen type XI alpha 1
- collagen XI, alpha-1 polypeptide
- collagen, type XI, alpha 1
- STL2
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
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- Akawi NA, Ali BR, Al-Gazali L. A response to Dr. Alzahrani's letter to the editor regarding the mechanism underlying fibrochondrogenesis. Gene. 2013 Oct 10;528(2):367-8. doi: 10.1016/j.gene.2013.07.038. Epub 2013 Jul 29. No abstract available. Citation on PubMed
- Alzahrani F, Alshammari MJ, Alkuraya FS. Molecular pathogenesis of fibrochondrogenesis: is it really simple COL11A1 deficiency? Gene. 2012 Dec 15;511(2):480-1. doi: 10.1016/j.gene.2012.09.069. Epub 2012 Sep 28. No abstract available. Citation on PubMed
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