The COL18A1 gene provides instructions for making a protein that forms collagen XVIII. Three COL18A1 proteins, called alpha 1 subunits, attach to each other to form collagen XVIII. Collagen XVIII is found in the basement membranes of tissues throughout the body. Basement membranes are thin, sheet-like structures that separate and support cells in these tissues.
There are three versions (isoforms) of the alpha 1 subunit of collagen XVIII, which form three different lengths of the collagen XVIII protein. The short version of collagen XVIII is found in basement membranes throughout the body, including several parts of the eye. The two longer versions are found primarily in the liver. In addition, a piece of collagen XVIII can be cut off to form the protein endostatin. Endostatin is able to block the formation of blood vessels (angiogenesis) and is known as an anti-angiogenic factor.
Little is known about the function of collagen XVIII, but it appears that all of the isoforms are involved in normal development of the eye.
Health Conditions Related to Genetic Changes
At least a dozen mutations in the COL18A1 gene have been identified in people with Knobloch syndrome, a condition characterized by severe vision problems and a skull defect called an occipital encephalocele. Most COL18A1 gene mutations lead to an abnormally short version of the genetic blueprint used to make the alpha 1 subunit of collagen XVIII. There are a few other mutations that replace single protein building blocks (amino acids) in the protein sequence. Although the process is unclear, the COL18A1 gene mutations result in the loss of collagen XVIII. Most COL18A1 gene mutations affect all isoforms of collagen XVIII, but at least one mutation affects only the short isoform. The loss of one or all isoforms of the collagen XVIII protein likely causes the signs and symptoms of Knobloch syndrome. It is unclear whether endostatin is involved in this condition.More About This Health Condition
Other Names for This Gene
- antiangiogenic agent
- collagen alpha-1(XVIII) chain
- collagen type XVIII alpha 1
- collagen, type XVIII, alpha 1
- multi-functional protein MFP
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Edwards Y. Structure and expression of mammalian carbonic anhydrases. Biochem Soc Trans. 1990 Apr;18(2):171-5. Review. Citation on PubMed
- Fukai N, Eklund L, Marneros AG, Oh SP, Keene DR, Tamarkin L, Niemelä M, Ilves M, Li E, Pihlajaniemi T, Olsen BR. Lack of collagen XVIII/endostatin results in eye abnormalities. EMBO J. 2002 Apr 2;21(7):1535-44. Citation on PubMed or Free article on PubMed Central
- Passos-Bueno MR, Suzuki OT, Armelin-Correa LM, Sertié AL, Errera FI, Bagatini K, Kok F, Leite KR. Mutations in collagen 18A1 and their relevance to the human phenotype. An Acad Bras Cienc. 2006 Mar;78(1):123-31. Epub 2006 Mar 8. Review. Citation on PubMed
- Sertié AL, Sossi V, Camargo AA, Zatz M, Brahe C, Passos-Bueno MR. Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome). Hum Mol Genet. 2000 Aug 12;9(13):2051-8. Citation on PubMed
- Suzuki O, Kague E, Bagatini K, Tu H, Heljasvaara R, Carvalhaes L, Gava E, de Oliveira G, Godoi P, Oliva G, Kitten G, Pihlajaniemi T, Passos-Bueno MR. Novel pathogenic mutations and skin biopsy analysis in Knobloch syndrome. Mol Vis. 2009;15:801-9. Epub 2009 Apr 23. Citation on PubMed or Free article on PubMed Central
- Suzuki OT, Sertié AL, Der Kaloustian VM, Kok F, Carpenter M, Murray J, Czeizel AE, Kliemann SE, Rosemberg S, Monteiro M, Olsen BR, Passos-Bueno MR. Molecular analysis of collagen XVIII reveals novel mutations, presence of a third isoform, and possible genetic heterogeneity in Knobloch syndrome. Am J Hum Genet. 2002 Dec;71(6):1320-9. Epub 2002 Nov 1. Citation on PubMed or Free article on PubMed Central