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Genetics Home Reference: your guide to understanding genetic conditions
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C3

Reviewed February 2011

What is the official name of the C3 gene?

The official name of this gene is “complement component 3.”

C3 is the gene's official symbol. The C3 gene is also known by other names, listed below.

What is the normal function of the C3 gene?

The C3 gene provides instructions for making a protein called complement component 3 (or simply C3). This protein plays a key role in a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues.

The C3 protein is essential for activating the complement system. The presence of foreign invaders triggers the C3 protein to be cut (cleaved) into two smaller pieces. One of these pieces, called C3b, interacts with several other proteins on the surface of cells to trigger the complement system's response. This process must be carefully regulated so the complement system targets only unwanted materials and does not attack the body's healthy cells.

Researchers have identified two major forms (allotypes) of the C3 protein, which are known as C3S and C3F. In the general population, C3S is more common than C3F. The two allotypes differ by a single protein building block (amino acid), although it is unclear whether they function differently.

Does the C3 gene share characteristics with other genes?

The C3 gene belongs to a family of genes called complement (complement system). It also belongs to a family of genes called endogenous ligands (endogenous ligands).

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 C3 gene related to health conditions?

dense deposit disease - caused by mutations in the C3 gene

At least one mutation in the C3 gene has been found to cause dense deposit disease. This condition, which was formerly known as membranoproliferative glomerulonephritis type II, is a form of progressive kidney (renal) disease. The identified mutation deletes two amino acids from the C3 protein. This genetic change is described as a "gain-of-function" mutation because it leads to abnormal activation of the complement system. The overactive system creates debris that builds up in and damages certain structures in the kidneys. These structures, called glomeruli, are clusters of tiny blood vessels that help filter waste products from the blood. Damage to glomeruli prevents the kidneys from filtering waste products normally and can lead to end-stage renal disease (ESRD), a life-threatening failure of kidney function.

Several normal variants (polymorphisms) in the C3 gene have also been associated with an increased risk of developing dense deposit disease. In particular, the C3F allotype is seen more frequently in people with this condition than in the general population. Researchers are working to determine how the C3F allotype influences disease risk.

other disorders - caused by mutations in the C3 gene

At least eight mutations in the C3 gene have been found to cause C3 deficiency, a condition characterized by recurrent bacterial infections. The genetic changes responsible for C3 deficiency are described as "loss-of-function" mutations because they prevent normal activation of the complement system. As a result, the immune system is less able to protect the body against foreign invaders (such as bacteria).

Several mutations in the C3 gene also appear to increase the risk of a kidney disease called atypical hemolytic-uremic syndrome. Studies suggest that many of these genetic changes alter the C3 protein's ability to attach (bind) to other proteins, leading to abnormal activation of the complement system. The overactive system attacks endothelial cells, which line small blood vessels in the kidneys. Damage to these cells often leads to kidney failure and ESRD in people with atypical hemolytic-uremic syndrome.

Although genetic changes increase the risk of atypical hemolytic-uremic syndrome, studies suggest that they are often not sufficient to cause the disease. In people with C3 gene mutations, the signs and symptoms of the disorder may be triggered by factors such as certain medications (such as anti-cancer drugs), chronic diseases, viral or bacterial infections, cancers, organ transplantation, or pregnancy.

Changes in the C3 gene have also been associated with an increased risk of an eye disorder called age-related macular degeneration (AMD), which is a leading cause of vision loss in the elderly. Specifically, the C3F allotype is seen more frequently in people with AMD than in the general population. It is unclear how the C3F allotype is related to the risk of AMD, although the condition can be associated with uncontrolled activation of the complement system. A combination of genetic and environmental factors likely determines the risk of developing this complex eye disorder.

Where is the C3 gene located?

Cytogenetic Location: 19p13.3-p13.2

Molecular Location on chromosome 19: base pairs 6,677,834 to 6,720,650

The C3 gene is located on the short (p) arm of chromosome 19 between positions 13.3 and 13.2.

The C3 gene is located on the short (p) arm of chromosome 19 between positions 13.3 and 13.2.

More precisely, the C3 gene is located from base pair 6,677,834 to base pair 6,720,650 on chromosome 19.

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 C3?

You and your healthcare professional may find the following resources about C3 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 C3 gene or gene products?

  • acylation-stimulating protein cleavage product
  • AHUS5
  • ARMD9
  • ASP
  • C3a
  • C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1
  • C3b
  • CO3_HUMAN
  • complement C3
  • CPAMD1

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 C3?

acids ; amino acid ; Asp ; atypical ; bacteria ; cancer ; chronic ; deficiency ; domain ; endothelial cells ; end-stage renal disease ; ESRD ; gene ; hydrolysis ; immune response ; immune system ; inflammation ; innate immunity ; kidney ; mutation ; population ; protein ; renal ; renal disease ; stage ; syndrome

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

References

  • Botto M, Fong KY, So AK, Rudge A, Walport MJ. Molecular basis of hereditary C3 deficiency. J Clin Invest. 1990 Oct;86(4):1158-63. (http://www.ncbi.nlm.nih.gov/pubmed/2212005?dopt=Abstract)
  • Frémeaux-Bacchi V, Miller EC, Liszewski MK, Strain L, Blouin J, Brown AL, Moghal N, Kaplan BS, Weiss RA, Lhotta K, Kapur G, Mattoo T, Nivet H, Wong W, Gie S, Hurault de Ligny B, Fischbach M, Gupta R, Hauhart R, Meunier V, Loirat C, Dragon-Durey MA, Fridman WH, Janssen BJ, Goodship TH, Atkinson JP. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood. 2008 Dec 15;112(13):4948-52. doi: 10.1182/blood-2008-01-133702. Epub 2008 Sep 16. (http://www.ncbi.nlm.nih.gov/pubmed/18796626?dopt=Abstract)
  • Janssen BJ, Gros P. Structural insights into the central complement component C3. Mol Immunol. 2007 Jan;44(1-3):3-10. Epub 2006 Jul 27. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16875735?dopt=Abstract)
  • Maller JB, Fagerness JA, Reynolds RC, Neale BM, Daly MJ, Seddon JM. Variation in complement factor 3 is associated with risk of age-related macular degeneration. Nat Genet. 2007 Oct;39(10):1200-1. Epub 2007 Sep 2. (http://www.ncbi.nlm.nih.gov/pubmed/17767156?dopt=Abstract)
  • Martínez-Barricarte R, Heurich M, Valdes-Cañedo F, Vazquez-Martul E, Torreira E, Montes T, Tortajada A, Pinto S, Lopez-Trascasa M, Morgan BP, Llorca O, Harris CL, Rodríguez de Córdoba S. Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation. J Clin Invest. 2010 Oct;120(10):3702-12. doi: 10.1172/JCI43343. Epub 2010 Sep 13. (http://www.ncbi.nlm.nih.gov/pubmed/20852386?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/718)
  • Singer L, Colten HR, Wetsel RA. Complement C3 deficiency: human, animal, and experimental models. Pathobiology. 1994;62(1):14-28. Review. (http://www.ncbi.nlm.nih.gov/pubmed/8031472?dopt=Abstract)
  • Yates JR, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H, Clayton DG, Hayward C, Morgan J, Wright AF, Armbrecht AM, Dhillon B, Deary IJ, Redmond E, Bird AC, Moore AT; Genetic Factors in AMD Study Group. Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med. 2007 Aug 9;357(6):553-61. Epub 2007 Jul 18. (http://www.ncbi.nlm.nih.gov/pubmed/17634448?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: February 2011
Published: February 23, 2015