Normal Function
The CFHR5 gene provides instructions for making a protein called complement factor H-related 5. The precise function of this protein is unknown. However, its structure is similar to that of a protein called complement factor H (which is produced from the CFH gene). This similarity provides clues to the probable function of complement factor H-related 5.
Complement factor H regulates 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. This system must be carefully regulated so it targets only unwanted materials and does not damage the body's healthy cells. Complement factor H helps to protect healthy cells by preventing the complement system from being turned on (activated) when it is not needed. Studies suggest that complement factor H-related 5 also plays a role in controlling the complement system.
Health Conditions Related to Genetic Changes
Atypical hemolytic-uremic syndrome
MedlinePlus Genetics provides information about Atypical hemolytic-uremic syndrome
More About This Health ConditionC3 glomerulopathy
Several mutations in the CFHR5 gene have been found to cause a rare form of kidney disease called C3 glomerulopathy. This disorder damages the kidneys and can lead to end-stage renal disease (ESRD), a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.
The most common CFHR5 gene mutation has been identified in people from the Mediterranean island of Cyprus. This genetic change abnormally copies (duplicates) regions of the CFHR5 gene known as exons 2 and 3. The duplication alters the structure and function of complement factor H-related 5, preventing it from regulating the complement system effectively. As a result, the complement system becomes overactive, which damages structures called glomeruli in the kidneys. These structures 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 ESRD.
Several other changes involving the CFHR5 gene do not cause C3 glomerulopathy directly but appear to increase the likelihood of developing the disorder. It is unclear how variations in this gene affect the regulation of the complement system, and researchers are still working to determine how these genetic changes contribute to disease risk.
More About This Health ConditionAge-related macular degeneration
MedlinePlus Genetics provides information about Age-related macular degeneration
More About This Health ConditionOther Names for This Gene
- CFHL5
- complement factor H-related 5
- complement factor H-related protein 5
- factor H-related protein 5
- FHR-5
- FHR5
- FHR5_HUMAN
- FLJ10549
- MGC133240
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Abrera-Abeleda MA, Nishimura C, Smith JL, Sethi S, McRae JL, Murphy BF, Silvestri G, Skerka C, Jozsi M, Zipfel PF, Hageman GS, Smith RJ. Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease). J Med Genet. 2006 Jul;43(7):582-9. doi: 10.1136/jmg.2005.038315. Epub 2005 Nov 18. Citation on PubMed or Free article on PubMed Central
- Athanasiou Y, Voskarides K, Gale DP, Damianou L, Patsias C, Zavros M, Maxwell PH, Cook HT, Demosthenous P, Hadjisavvas A, Kyriacou K, Zouvani I, Pierides A, Deltas C. Familial C3 glomerulopathy associated with CFHR5 mutations: clinical characteristics of 91 patients in 16 pedigrees. Clin J Am Soc Nephrol. 2011 Jun;6(6):1436-46. doi: 10.2215/CJN.09541010. Epub 2011 May 12. Citation on PubMed or Free article on PubMed Central
- Deltas C, Gale D, Cook T, Voskarides K, Athanasiou Y, Pierides A. C3 glomerulonephritis/CFHR5 nephropathy is an endemic disease in Cyprus: clinical and molecular findings in 21 families. Adv Exp Med Biol. 2013;735:189-96. doi: 10.1007/978-1-4614-4118-2_12. Citation on PubMed
- Gale DP, de Jorge EG, Cook HT, Martinez-Barricarte R, Hadjisavvas A, McLean AG, Pusey CD, Pierides A, Kyriacou K, Athanasiou Y, Voskarides K, Deltas C, Palmer A, Fremeaux-Bacchi V, de Cordoba SR, Maxwell PH, Pickering MC. Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis. Lancet. 2010 Sep 4;376(9743):794-801. doi: 10.1016/S0140-6736(10)60670-8. Epub 2010 Aug 25. Citation on PubMed or Free article on PubMed Central
- Gale DP, Maxwell PH. C3 glomerulonephritis and CFHR5 nephropathy. Nephrol Dial Transplant. 2013 Feb;28(2):282-8. doi: 10.1093/ndt/gfs441. Epub 2012 Nov 2. Citation on PubMed
- Gale DP, Pickering MC. Regulating complement in the kidney: insights from CFHR5 nephropathy. Dis Model Mech. 2011 Nov;4(6):721-6. doi: 10.1242/dmm.008052. Citation on PubMed or Free article on PubMed Central
- Xiao X, Pickering MC, Smith RJ. C3 glomerulopathy: the genetic and clinical findings in dense deposit disease and C3 glomerulonephritis. Semin Thromb Hemost. 2014 Jun;40(4):465-71. doi: 10.1055/s-0034-1376334. Epub 2014 May 5. Citation on PubMed
- Zipfel PF, Skerka C, Chen Q, Wiech T, Goodship T, Johnson S, Fremeaux-Bacchi V, Nester C, de Cordoba SR, Noris M, Pickering M, Smith R. The role of complement in C3 glomerulopathy. Mol Immunol. 2015 Sep;67(1):21-30. doi: 10.1016/j.molimm.2015.03.012. Epub 2015 Apr 28. Citation on PubMed
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