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Genetics Home Reference: your guide to understanding genetic conditions
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MEFV

Reviewed September 2008

What is the official name of the MEFV gene?

The official name of this gene is “Mediterranean fever.”

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

What is the normal function of the MEFV gene?

The MEFV gene provides instructions for making a protein called pyrin (also known as marenostrin). Although pyrin's function is not fully understood, it likely assists in keeping the inflammation process under control. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body stops the inflammatory response to prevent damage to its own cells and tissues.

Pyrin is produced in certain white blood cells (neutrophils, eosinophils, and monocytes) that play a role in inflammation and in fighting infection. Pyrin may direct the migration of white blood cells to sites of inflammation and stop or slow the inflammatory response when it is no longer needed. Pyrin also interacts with other molecules involved in fighting infection and in the inflammatory response. Research indicates that pyrin helps regulate inflammation by interacting with the cytoskeleton, the structural framework that helps to define the shape, size, and movement of a cell.

Does the MEFV gene share characteristics with other genes?

The MEFV gene belongs to a family of genes called TRIM (tripartite motif-containing).

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 MEFV gene related to health conditions?

familial Mediterranean fever - caused by mutations in the MEFV gene

More than 80 MEFV gene mutations that cause familial Mediterranean fever have been identified. A few mutations delete small amounts of DNA from the MEFV gene, which can lead to an abnormally small, nonfunctional protein. Most MEFV gene mutations, however, change one of the protein building blocks (amino acids) used to make pyrin. The most common mutation replaces the amino acid methionine with the amino acid valine at protein position 694 (written as Met694Val or M694V). Among people with familial Mediterranean fever, this particular mutation is also associated with an increased risk of developing amyloidosis, a complication in which abnormal protein deposits can lead to kidney failure. Some evidence suggests that variations in another gene, called SAA1, can further modify the risk of developing amyloidosis among people with the M694V mutation.

MEFV gene mutations lead to reduced amounts of pyrin or a malformed pyrin protein that cannot function properly. As a result, pyrin cannot perform its presumed role in controlling inflammation, leading to an inappropriate or prolonged inflammatory response. Fever and inflammation in the abdomen, chest, joints, or skin are signs of familial Mediterranean fever.

Where is the MEFV gene located?

Cytogenetic Location: 16p13.3

Molecular Location on chromosome 16: base pairs 3,242,027 to 3,256,647

The MEFV gene is located on the short (p) arm of chromosome 16 at position 13.3.

The MEFV gene is located on the short (p) arm of chromosome 16 at position 13.3.

More precisely, the MEFV gene is located from base pair 3,242,027 to base pair 3,256,647 on chromosome 16.

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 MEFV?

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

  • FMF
  • marenostrin
  • MEF
  • MEFV_HUMAN
  • MRST
  • pyrin
  • TRIM20

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 MEFV?

acids ; amino acid ; amyloidosis ; cell ; complication ; cytoskeleton ; DNA ; eosinophils ; familial ; fever ; gene ; immune system ; infection ; inflammation ; injury ; kidney ; methionine ; mutation ; neutrophils ; protein ; tissue ; valine ; white blood cells

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

References

  • Aksentijevich I, Torosyan Y, Samuels J, Centola M, Pras E, Chae JJ, Oddoux C, Wood G, Azzaro MP, Palumbo G, Giustolisi R, Pras M, Ostrer H, Kastner DL. Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population. Am J Hum Genet. 1999 Apr;64(4):949-62. (http://www.ncbi.nlm.nih.gov/pubmed/10090880?dopt=Abstract)
  • Bakkaloglu A. Familial Mediterranean fever. Pediatr Nephrol. 2003 Sep;18(9):853-9. Epub 2003 Jun 27. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12836090?dopt=Abstract)
  • Chae JJ, Wood G, Masters SL, Richard K, Park G, Smith BJ, Kastner DL. The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9982-7. Epub 2006 Jun 19. (http://www.ncbi.nlm.nih.gov/pubmed/16785446?dopt=Abstract)
  • Delibaş A, Oner A, Balci B, Demircin G, Bulbul M, Bek K, Erdoğan O, Baysun S, Yilmaz E. Genetic risk factors of amyloidogenesis in familial Mediterranean fever. Am J Nephrol. 2005 Sep-Oct;25(5):434-40. Epub 2005 Aug 23. (http://www.ncbi.nlm.nih.gov/pubmed/16118480?dopt=Abstract)
  • OMIM: FAMILIAL MEDITERRANEAN FEVER GENE (http://omim.org/entry/608107)
  • Gershoni-Baruch R, Brik R, Zacks N, Shinawi M, Lidar M, Livneh A. The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever. Arthritis Rheum. 2003 Apr;48(4):1149-55. (http://www.ncbi.nlm.nih.gov/pubmed/12687559?dopt=Abstract)
  • Mansfield E, Chae JJ, Komarow HD, Brotz TM, Frucht DM, Aksentijevich I, Kastner DL. The familial Mediterranean fever protein, pyrin, associates with microtubules and colocalizes with actin filaments. Blood. 2001 Aug 1;98(3):851-9. (http://www.ncbi.nlm.nih.gov/pubmed/11468188?dopt=Abstract)
  • Medlej-Hashim M, Delague V, Chouery E, Salem N, Rawashdeh M, Lefranc G, Loiselet J, Mégarbané A. Amyloidosis in familial Mediterranean fever patients: correlation with MEFV genotype and SAA1 and MICA polymorphisms effects. BMC Med Genet. 2004 Feb 10;5:4. (http://www.ncbi.nlm.nih.gov/pubmed/15018633?dopt=Abstract)
  • Mikula M, Buller A, Sun W, Strom CM. Prevalence of known mutations in the familial Mediterranean fever gene (MEFV) in various carrier screening populations. Genet Med. 2008 May;10(5):349-52. doi: 10.1097/GIM.0b013e3181723cc8. (http://www.ncbi.nlm.nih.gov/pubmed/18496034?dopt=Abstract)
  • Milhavet F, Cuisset L, Hoffman HM, Slim R, El-Shanti H, Aksentijevich I, Lesage S, Waterham H, Wise C, Sarrauste de Menthiere C, Touitou I. The infevers autoinflammatory mutation online registry: update with new genes and functions. Hum Mutat. 2008 Jun;29(6):803-8. doi: 10.1002/humu.20720. (http://www.ncbi.nlm.nih.gov/pubmed/18409191?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4210)
  • Notarnicola C, Didelot MN, Koné-Paut I, Seguret F, Demaille J, Touitou I. Reduced MEFV messenger RNA expression in patients with familial Mediterranean fever. Arthritis Rheum. 2002 Oct;46(10):2785-93. (http://www.ncbi.nlm.nih.gov/pubmed/12384939?dopt=Abstract)
  • Papin S, Cuenin S, Agostini L, Martinon F, Werner S, Beer HD, Grütter C, Grütter M, Tschopp J. The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing. Cell Death Differ. 2007 Aug;14(8):1457-66. Epub 2007 Apr 13. (http://www.ncbi.nlm.nih.gov/pubmed/17431422?dopt=Abstract)
  • Rabinovitch E, Harats D, Yaron P, Luvish T, Lidar M, Kedem R, Shaish A, Ben-Dov I, Livneh A. Familial Mediterranean fever gene and protection against asthma. Ann Allergy Asthma Immunol. 2007 Dec;99(6):517-21. doi: 10.1016/S1081-1206(10)60380-8. (http://www.ncbi.nlm.nih.gov/pubmed/18219832?dopt=Abstract)
  • Ross JJ. Goats, germs, and fever: Are the pyrin mutations responsible for familial Mediterranean fever protective against Brucellosis? Med Hypotheses. 2007;68(3):499-501. Epub 2006 Sep 26. (http://www.ncbi.nlm.nih.gov/pubmed/17005326?dopt=Abstract)
  • Stoffman N, Magal N, Shohat T, Lotan R, Koman S, Oron A, Danon Y, Halpern GJ, Lifshitz Y, Shohat M. Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups. Eur J Hum Genet. 2000 Apr;8(4):307-10. (http://www.ncbi.nlm.nih.gov/pubmed/10854115?dopt=Abstract)
  • Telatar M, Grody WW. Molecular genetic testing for familial Mediterranean fever. Mol Genet Metab. 2000 Sep-Oct;71(1-2):256-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11001819?dopt=Abstract)
  • Yepiskoposyan L, Harutyunyan A. Population genetics of familial Mediterranean fever: a review. Eur J Hum Genet. 2007 Sep;15(9):911-6. Epub 2007 Jun 13. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17568393?dopt=Abstract)
  • Yu JW, Fernandes-Alnemri T, Datta P, Wu J, Juliana C, Solorzano L, McCormick M, Zhang Z, Alnemri ES. Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol Cell. 2007 Oct 26;28(2):214-27. (http://www.ncbi.nlm.nih.gov/pubmed/17964261?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 2008
Published: November 17, 2014