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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed June 2011

What is the official name of the COL18A1 gene?

The official name of this gene is “collagen type XVIII alpha 1.”

COL18A1 is the gene's official symbol. The COL18A1 gene is also known by other names, listed below.

What is the normal function of the COL18A1 gene?

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.

Does the COL18A1 gene share characteristics with other genes?

The COL18A1 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? ( in the Handbook.

How are changes in the COL18A1 gene related to health conditions?

Knobloch syndrome - caused by mutations in the COL18A1 gene

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.

Where is the COL18A1 gene located?

Cytogenetic Location: 21q22.3

Molecular Location on chromosome 21: base pairs 45,405,137 to 45,513,720

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

The COL18A1 gene is located on the long (q) arm of chromosome 21 at position 22.3.

The COL18A1 gene is located on the long (q) arm of chromosome 21 at position 22.3.

More precisely, the COL18A1 gene is located from base pair 45,405,137 to base pair 45,513,720 on chromosome 21.

See How do geneticists indicate the location of a gene? ( in the Handbook.

Where can I find additional information about COL18A1?

You and your healthcare professional may find the following resources about COL18A1 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 COL18A1 gene or gene products?

  • antiangiogenic agent
  • collagen alpha-1(XVIII) chain
  • collagen, type XVIII, alpha 1
  • endostatin
  • FLJ27325
  • FLJ34914
  • KNO
  • KNO1
  • KS
  • MGC74745
  • multi-functional protein MFP

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding COL18A1?

acids ; angiogenesis ; basement membranes ; collagen ; gene ; isoforms ; mutation ; protein ; protein sequence ; subunit ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Edwards Y. Structure and expression of mammalian carbonic anhydrases. Biochem Soc Trans. 1990 Apr;18(2):171-5. Review. (
  • 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. (
  • NCBI Gene (
  • 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. (
  • 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. (
  • 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. (
  • 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. (


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? ( in the Handbook.

Reviewed: June 2011
Published: February 1, 2016