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Genetics Home Reference: your guide to understanding genetic conditions
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COL4A1

Reviewed September 2011

What is the official name of the COL4A1 gene?

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

COL4A1 is the gene's official symbol. The COL4A1 gene is also known by other names, listed below.

What is the normal function of the COL4A1 gene?

The COL4A1 gene provides instructions for making one component of type IV collagen, which is a flexible protein important in the structure of many tissues throughout the body. Specifically, this gene makes the alpha1(IV) chain of type IV collagen. This chain combines with another alpha1 chain and a different type of alpha (IV) chain called alpha2 to make a complete type IV collagen alpha1-1-2 molecule. Type IV collagen molecules attach to each other to form complex protein networks. These protein networks are the main component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen alpha1-1-2 networks play an important role in the basement membranes in virtually all tissues throughout the body, particularly the basement membranes surrounding the body's blood vessels (vasculature). The type IV collagen network helps the basement membranes interact with nearby cells, playing a role in cell movement (migration), cell growth and division (proliferation), cell maturation (differentiation), and the survival of cells.

Does the COL4A1 gene share characteristics with other genes?

The COL4A1 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 COL4A1 gene related to health conditions?

COL4A1-related brain small-vessel disease - caused by mutations in the COL4A1 gene

Mutations in the COL4A1 gene have been found to cause COL4A1-related brain small-vessel disease. This condition is part of a group of conditions called COL4A1-related disorders that have overlapping signs and symptoms involving fragile blood vessels. COL4A1-related brain small-vessel disease is characterized by stroke and eye abnormalities. Most of the identified COL4A1 gene mutations that cause COL4A1-related brain small-vessel disease change one of the protein building blocks (amino acids) used to make the alpha1(IV) chain of type IV collagen. Specifically, the mutations replace the amino acid glycine with a different amino acid at one of various places in this collagen chain. The substitution of another amino acid for glycine in the alpha1(IV) chain prevents this chain from combining with other chains to form a complete type IV collagen molecule. This alteration in type IV collagen prevents protein networks from forming and basement membranes from developing properly, which causes the tissues they support to weaken. Blood vessels throughout the body become fragile, leading to the signs and symptoms of COL4A1-related brain small-vessel disease.

It is unclear how mutations in the COL4A1 gene can lead to different disorders. It is likely that mutations in different regions of this gene play a role in the development of the various signs and symptoms of the COL4A1-related disorders. Other genetic changes as well as environmental factors may also contribute to the features of the different COL4A1-related disorders.

familial porencephaly - caused by mutations in the COL4A1 gene

Mutations in the COL4A1 gene have been found to cause familial porencephaly, another member of the group of vascular conditions called COL4A1-related disorders. Familial porencephaly is characterized by early stroke and brain cysts. Most of the identified COL4A1 gene mutations that cause familial porencephaly change one of the amino acids used to make the alpha1(IV) chain of type IV collagen. Specifically, the mutations replace the amino acid glycine with a different amino acid at one of various places in this collagen chain. The substitution of another amino acid for glycine in the alpha1(IV) chain prevents this chain from combining with other chains to form a complete type IV collagen molecule. This alteration in type IV collagen prevents protein networks from forming and basement membranes from developing properly, which causes the tissues they support to weaken. Blood vessels in the brain become fragile, leading to the signs and symptoms of familial porencephaly.

hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome - caused by mutations in the COL4A1 gene

Mutations in the COL4A1 gene have been found to cause hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome, a third member of the group of conditions called COL4A1-related disorders. HANAC syndrome is characterized by weakened blood vessels in the brain and throughout the body, kidney disease, muscle cramps, and eye abnormalities. Most of the identified COL4A1 gene mutations that cause HANAC syndrome change one of the amino acids used to make the alpha1(IV) chain of type IV collagen. Specifically, the mutations replace the amino acid glycine with a different amino acid at one of various places in this collagen chain. The substitution of another amino acid for glycine in the alpha1(IV) chain prevents this chain from combining with other chains to form a complete type IV collagen molecule. This alteration in type IV collagen prevents protein networks from forming and basement membranes from developing properly. As a result, the tissues they support weaken, particularly in the eyes and kidneys. Fragile blood vessels and weakened basement membranes lead to the signs and symptoms of HANAC syndrome.

Where is the COL4A1 gene located?

Cytogenetic Location: 13q34

Molecular Location on chromosome 13: base pairs 110,148,962 to 110,307,148

The COL4A1 gene is located on the long (q) arm of chromosome 13 at position 34.

The COL4A1 gene is located on the long (q) arm of chromosome 13 at position 34.

More precisely, the COL4A1 gene is located from base pair 110,148,962 to base pair 110,307,148 on chromosome 13.

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 COL4A1?

You and your healthcare professional may find the following resources about COL4A1 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 COL4A1 gene or gene products?

  • arresten
  • CO4A1_HUMAN
  • COL4A1 NC1 domain
  • collagen alpha-1(IV) chain
  • collagen alpha-1(IV) chain preproprotein
  • collagen IV, alpha-1 polypeptide
  • collagen of basement membrane, alpha-1 chain

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 COL4A1?

acids ; amino acid ; basement membrane ; basement membranes ; cell ; collagen ; cysts ; differentiation ; domain ; familial ; gene ; glycine ; hereditary ; kidney ; molecule ; nephropathy ; proliferation ; protein ; substitution ; syndrome ; vascular

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

References

  • Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, Marro B, Ronco P. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. Neurology. 2009 Dec 1;73(22):1873-82. doi: 10.1212/WNL.0b013e3181c3fd12. (http://www.ncbi.nlm.nih.gov/pubmed/19949034?dopt=Abstract)
  • Breedveld G, de Coo IF, Lequin MH, Arts WF, Heutink P, Gould DB, John SW, Oostra B, Mancini GM. Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. J Med Genet. 2006 Jun;43(6):490-5. Epub 2005 Aug 17. (http://www.ncbi.nlm.nih.gov/pubmed/16107487?dopt=Abstract)
  • OMIM: COLLAGEN, TYPE IV, ALPHA-1 (http://omim.org/entry/120130)
  • Lanfranconi S, Markus HS. COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. Stroke. 2010 Aug;41(8):e513-8. doi: 10.1161/STROKEAHA.110.581918. Epub 2010 Jun 17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20558831?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1282)
  • Vahedi K, Alamowitch S. Clinical spectrum of type IV collagen (COL4A1) mutations: a novel genetic multisystem disease. Curr Opin Neurol. 2011 Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21157337?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: September 2011
Published: October 27, 2014