MEFV Gene

The MEFV gene (MEFV is the acronym for "Mediterranean fever gene") is a protein-coding gene located on chromosome 16p13.3. The gene product is also known as pyrin (cryopyrin) or marenostrin (lat.: mare nostrum for Mediterranean) and is an important modulator of innate immunity. The resulting functional impairment of the protein encoded by this gene leads to the triggering of a systemic inflammatory reaction.

Mutations in this gene are associated with familial Mediterranean fever(Mediterranean fever), a hereditary periodic fever syndrome frequently found in the Mediterranean region. An important paralog of this gene is TRIM8. The encoded protein pyrin is involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. It is a key element of the inflammasome and is thus involved in the autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1, ATG16L1 and ATG8 family members.

Pyrin recognizes specific autophagy targets, coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. It acts as an autophagy receptor for the degradation of several inflammasome components, including the coding products of CASP1, NLRP1 and NLRP3. It thus prevents excessive interleukin-1beta and interleukin-18-mediated inflammation.

However, pyrin can also have a positive effect on the inflammatory pathway by acting as an innate immune system sensor that triggers PYCARD/ASC patch formation, caspase-1 activation and IL1B and IL18 production.

Pyrin is required for PSTPIP1-induced PYCARD/ASC oligomerization and inflammasome formation. Recruits PSTPIP1 to inflammasomes and is required for PSTPIP1 oligomerization.

1. Aldea A et al. (2004) A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: An unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder? Am J Med Genet 124A: 67-73
2. Delplanque M et al. (2022) Is neutrophilic dermatosis a manifestation of familial Mediterranean fever? Scand J Rheumatol 51:42-49.
3. Gershoni-Baruch R et al. (2003) Prevalence and significance of mutations in the familial Mediterranean fever gene in Henoch-Schonlein purpura. J Pediatr 143: 658-661.
4. Tufan A et al. (2020) Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review. Turk J Med Sci 50(SI-2):1591-1610.