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Genetics Home Reference: your guide to understanding genetic conditions
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COL11A2

Reviewed July 2008

What is the official name of the COL11A2 gene?

The official name of this gene is “collagen, type XI, alpha 2.”

COL11A2 is the gene's official symbol. The COL11A2 gene is also known by other names, listed below.

What is the normal function of the COL11A2 gene?

The COL11A2 gene provides instructions for making one component of type XI collagen, called the pro-alpha2(XI) chain. Type XI collagen adds 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 clear gel that fills the eyeball (the vitreous), the inner ear, and the center portion of the discs between the vertebrae in the spine (nucleus pulposus).

To construct type XI collagen, the pro-alpha2(XI) chain combines with two other collagen chains (pro-alpha1(XI) and pro-alpha1(II)) to form a procollagen molecule. These triple-stranded, ropelike procollagen molecules are then processed by enzymes in the cell. Once processed, procollagen molecules leave the cell and arrange themselves into long, thin fibrils that link to one another (cross-link) in the spaces around cells. The cross-linkages result in the formation of very strong mature type XI collagen fibers.

Type XI collagen also helps maintain the spacing and diameter of type II collagen fibrils. Type II collagen is an important component of the eye and mature cartilage tissue. The size and arrangement of type II collagen fibrils are essential for the normal structure of these tissues.

Does the COL11A2 gene share characteristics with other genes?

The COL11A2 gene belongs to a family of genes called COL (collagens).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the COL11A2 gene related to health conditions?

nonsyndromic deafness - caused by mutations in the COL11A2 gene

Mutations in the COL11A2 gene cause a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNA13. This type of deafness has been identified in two large families. In one family, a mutation replaces the amino acid arginine (a building block of proteins) with the amino acid cysteine at position 549 in the pro-alpha2(XI) chain of type XI collagen. This mutation is written as Arg549Cys. A second family has a mutation that substitutes the amino acid glutamic acid for the amino acid glycine at position 323 (written as Gly323Glu) in this protein. These mutations prevent the normal assembly of type XI collagen, which plays an important role in the structure and function of the inner ear.

otospondylomegaepiphyseal dysplasia - caused by mutations in the COL11A2 gene

Approximately 10 mutations in the COL11A2 gene have been found to cause otospondylomegaepiphyseal dysplasia (OSMED), a bone growth disorder. Most of these mutations result in a complete lack of pro-alpha2(XI) chains, which impairs the function of type XI collagen. Some mutations affect the production of the pro-alpha2(XI) chain and disrupt the assembly of type XI collagen. Type XI collagen is an important component of cartilage and other connective tissues, and its loss or impairment results in the characteristic signs and symptoms of OSMED.

Stickler syndrome - caused by mutations in the COL11A2 gene

Mutations in the COL11A2 gene can cause Stickler syndrome, a condition characterized by impaired skeletal development and hearing loss. COL11A2 mutations cause abnormal production of the pro-alpha2(XI) chain, part of type XI collagen. As a result, type XI collagen cannot function properly, causing the signs and symptoms of Stickler syndrome.

This type of Stickler syndrome is sometimes called the non-ocular type because it does not affect vision (unlike the other types of Stickler syndrome caused by mutations in other genes). The pro-alpha2(XI) chain is not found in the eyes and COL11A2 mutations do not affect vision. Instead, another type of collagen chain replaces pro-alpha2(XI) to form type XI collagen in the clear gel that fills the eyeball (the vitreous).

Weissenbacher-Zweymüller syndrome - caused by mutations in the COL11A2 gene

At least one mutation in the COL11A2 gene has been found to cause Weissenbacher-Zweymüller syndrome. This mutation replaces the amino acid glycine with the amino acid glutamic acid at position 955 in the collagen pro-alpha2(XI) chain (written as Gly955Glu). This mutation prevents collagen molecules from being assembled properly, which disrupts the structure of type XI collagen. These changes in type XI collagen result in the characteristic signs and symptoms of Weissenbacher-Zweymüller syndrome, including short stature, distinctive facial features, and occasionally, hearing loss.

other disorders - increased risk from variations of the COL11A2 gene

In some people, variations in the COL11A2 gene may increase the risk of developing osteoarthritis, a degenerative disease of joint cartilage. As a result of these genetic changes, incorrect amino acids are used in making the pro-alpha2(XI) chain of type XI collagen. The altered pro-alpha2(XI) chain may weaken collagen fibers, which could play a role in the erosion of cartilage in the joints, a characteristic feature of osteoarthritis.

Where is the COL11A2 gene located?

Cytogenetic Location: 6p21.3

Molecular Location on chromosome 6: base pairs 33,162,691 to 33,192,467

The COL11A2 gene is located on the short (p) arm of chromosome 6 at position 21.3.

The COL11A2 gene is located on the short (p) arm of chromosome 6 at position 21.3.

More precisely, the COL11A2 gene is located from base pair 33,162,691 to base pair 33,192,467 on chromosome 6.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about COL11A2?

You and your healthcare professional may find the following resources about COL11A2 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the COL11A2 gene or gene products?

  • DFNA13
  • HKE5
  • PARP
  • STL3

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding COL11A2?

acids ; amino acid ; arginine ; cartilage ; cell ; collagen ; cross-link ; cysteine ; degenerative ; diameter ; dysplasia ; gene ; glutamic acid ; glycine ; joint ; molecule ; mutation ; nucleus ; Pro ; protein ; short stature ; stature ; syndrome ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • OMIM: COLLAGEN, TYPE XI, ALPHA-2 (http://omim.org/entry/120290)
  • De Leenheer EM, Kunst HH, McGuirt WT, Prasad SD, Brown MR, Huygen PL, Smith RJ, Cremers CW. Autosomal dominant inherited hearing impairment caused by a missense mutation in COL11A2 (DFNA13). Arch Otolaryngol Head Neck Surg. 2001 Jan;127(1):13-7. (http://www.ncbi.nlm.nih.gov/pubmed/11177008?dopt=Abstract)
  • Finsterer J, Fellinger J. Nuclear and mitochondrial genes mutated in nonsyndromic impaired hearing. Int J Pediatr Otorhinolaryngol. 2005 May;69(5):621-47. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15850684?dopt=Abstract)
  • Jakkula E, Melkoniemi M, Kiviranta I, Lohiniva J, Räinä SS, Perälä M, Warman ML, Ahonen K, Kröger H, Göring HH, Ala-Kokko L. The role of sequence variations within the genes encoding collagen II, IX and XI in non-syndromic, early-onset osteoarthritis. Osteoarthritis Cartilage. 2005 Jun;13(6):497-507. (http://www.ncbi.nlm.nih.gov/pubmed/15922184?dopt=Abstract)
  • McGuirt WT, Prasad SD, Griffith AJ, Kunst HP, Green GE, Shpargel KB, Runge C, Huybrechts C, Mueller RF, Lynch E, King MC, Brunner HG, Cremers CW, Takanosu M, Li SW, Arita M, Mayne R, Prockop DJ, Van Camp G, Smith RJ. Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13). Nat Genet. 1999 Dec;23(4):413-9. (http://www.ncbi.nlm.nih.gov/pubmed/10581026?dopt=Abstract)
  • Melkoniemi M, Brunner HG, Manouvrier S, Hennekam R, Superti-Furga A, Kääriäinen H, Pauli RM, van Essen T, Warman ML, Bonaventure J, Miny P, Ala-Kokko L. Autosomal recessive disorder otospondylomegaepiphyseal dysplasia is associated with loss-of-function mutations in the COL11A2 gene. Am J Hum Genet. 2000 Feb;66(2):368-77. (http://www.ncbi.nlm.nih.gov/pubmed/10677296?dopt=Abstract)
  • Melkoniemi M, Koillinen H, Männikkö M, Warman ML, Pihlajamaa T, Kääriäinen H, Rautio J, Hukki J, Stofko JA, Cisneros GJ, Krakow D, Cohn DH, Kere J, Ala-Kokko L. Collagen XI sequence variations in nonsyndromic cleft palate, Robin sequence and micrognathia. Eur J Hum Genet. 2003 Mar;11(3):265-70. (http://www.ncbi.nlm.nih.gov/pubmed/12673280?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1302)
  • Pihlajamaa T, Prockop DJ, Faber J, Winterpacht A, Zabel B, Giedion A, Wiesbauer P, Spranger J, Ala-Kokko L. Heterozygous glycine substitution in the COL11A2 gene in the original patient with the Weissenbacher-Zweymüller syndrome demonstrates its identity with heterozygous OSMED (nonocular Stickler syndrome). Am J Med Genet. 1998 Nov 2;80(2):115-20. (http://www.ncbi.nlm.nih.gov/pubmed/9805126?dopt=Abstract)
  • Shpargel KB, Makishima T, Griffith AJ. Col11a1 and Col11a2 mRNA expression in the developing mouse cochlea: implications for the correlation of hearing loss phenotype with mutant type XI collagen genotype. Acta Otolaryngol. 2004 Apr;124(3):242-8. (http://www.ncbi.nlm.nih.gov/pubmed/15141750?dopt=Abstract)
  • Snead MP. Hereditary vitreopathy. Eye (Lond). 1996;10 ( Pt 6):653-63. Review. (http://www.ncbi.nlm.nih.gov/pubmed/9091360?dopt=Abstract)
  • Vuoristo MM, Pappas JG, Jansen V, Ala-Kokko L. A stop codon mutation in COL11A2 induces exon skipping and leads to non-ocular Stickler syndrome. Am J Med Genet A. 2004 Oct 1;130A(2):160-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15372529?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2008
Published: November 24, 2014