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MEFV

MEFV innate immunity regulator, pyrin

The MEFV gene provides instructions for producing the pyrin protein, which plays a crucial role in regulating the body's inflammatory response. The MEFV gene is responsible for encoding the pyrin protein, also known as marenostrin.

Chromosome 16p13.3 Autosomal recessive HGNC:6998 Tier C
MEFV 16p13.3 p arm q arm 16

MEFV is located on the short (p) arm of chromosome 16, at band 16p13.3. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 16 in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
MEFV is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
MEFV is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The MEFV gene provides the genetic blueprint for a protein called pyrin, also known as marenostrin, which is integral to the innate immune system. Its primary role involves the regulation of inflammation, a complex biological response to harmful stimuli such as pathogens and damaged cells. Proper functioning of the MEFV gene is vital for maintaining a balanced inflammatory response, preventing excessive or prolonged inflammation that could harm the body's own tissues.

What the gene does

Pyrin, the protein encoded by MEFV, likely contributes to maintaining appropriate control over inflammatory processes throughout the body. When injury or infection occurs, the immune system mobilises signalling molecules alongside white blood cells, directing them toward affected areas to eliminate microbial threats and support tissue healing. Once these objectives are achieved, the body must terminate the inflammatory cascade to avoid collateral damage to healthy cells. Specific white blood cells - including neutrophils, eosinophils, and monocytes - express pyrin and participate actively in both inflammation and pathogen defence. Evidence suggests pyrin may coordinate the movement of these cells toward inflammatory sites whilst also helping to curtail the response once it is no longer required. Additionally, pyrin combines with other molecular components to construct inflammasomes, multiprotein assemblies that participate in inflammatory signalling. Studies indicate that pyrin regulates inflammatory activity through interactions with the cytoskeleton, the internal scaffold determining cellular shape, dimensions, and motility.

Video: Genetics 101

Chromosome location

The MEFV gene is situated on the short arm of chromosome 16 at position 13.3, a region designated as 16p13.3. This precise genomic location ensures that the gene is correctly positioned within the human genome for its vital functions.

Protein structure

The MEFV protein, pyrin, is composed of several distinct functional regions spanning its 781 amino acids. At the N-terminal end, there is a Pyrin domain (amino acids 1-92) which is crucial for protein-protein interactions. Following this, multiple disordered regions (amino acids 93-226, 270-322, 336-373) offer flexibility to the protein structure. A B box-type zinc finger motif (amino acids 370-412) and a coiled-coil region (amino acids 413-442) are also present, which are important for specific protein interactions. A particular stretch (amino acids 420-582) is identified as essential for pyrin's ability to undergo homotrimerisation and induce pyroptosomes, which are complexes involved in inflammatory cell death. The protein also contains a nuclear localisation signal (amino acids 420-437) and a large B30.2/SPRY domain (amino acids 580-775) towards its C-terminus, which is thought to be involved in ligand recognition and protein interactions.

Domain map · 781 amino acids
Pyrin (1–92)Interaction with RELA (266–280)B box-type (370–412)Coiled coil (413–442)Nuclear localization signal (420–437)Required for homotrimerization and induction of pyroptosomes (420–582)B30.2/SPRY (580–775)Pyrin1–92Required for homotrime420–582B30.2/SPRY580–7751~391781
Domain - independent functional unit
Region - functional region
Zinc finger - zinc-binding structural motif
Region - functional region
Motif - short conserved sequence
🧬 Explore 3D structure on AlphaFold
UniProt:O15553Length:781 aaStructure:AlphaFold

Key variants

Numerous genetic changes, or variants, within the MEFV gene have been identified in individuals with related conditions. Some variants involve small deletions of DNA, which can lead to an abnormally short or non-functional protein. Other MEFV gene variants typically result in a single amino acid alteration within the pyrin protein. These variants can disrupt the normal function of pyrin, impairing its ability to regulate inflammation.

The table below shows the top 8 pathogenic or likely-pathogenic variants currently classified in ClinVar for MEFV.
View all on ClinVar →

Sample of pathogenic variants

8 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.2177T>C
single nucleotide variant
 p.Val726Ala Pathogenic/Likely pathogenic ★★☆☆ Acute febrile neutrophilic dermatosis
c.2282G>A
single nucleotide variant
 p.Arg761His Pathogenic/Likely pathogenic ★★☆☆ Acute febrile neutrophilic dermatosis
c.726C>A
single nucleotide variant
 p.Ser242Arg Pathogenic/Likely pathogenic ★★☆☆ Familial Mediterranean fever
c.1510C>T
single nucleotide variant
 p.Gln504Ter Pathogenic ★☆☆☆ Familial Mediterranean fever
c.214C>T
single nucleotide variant
 p.Gln72Ter Pathogenic ★☆☆☆ Familial Mediterranean fever
c.265del
Deletion
 p.Ala89fs Pathogenic ★☆☆☆ Familial Mediterranean fever
c.332G>A
single nucleotide variant
 p.Gly111Glu Pathogenic - Behcet disease
c.730G>A
single nucleotide variant
 p.Glu244Lys Pathogenic - Acute febrile neutrophilic dermatosis

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the MEFV gene are primarily associated with Familial Mediterranean fever. This inherited inflammatory disorder is typically passed down in an autosomal recessive manner, meaning an individual must inherit two copies of a pathogenic variant (one from each parent) to develop the condition. There are also rare autosomal dominant forms of Familial Mediterranean fever. Individuals carrying a single pathogenic variant are classified as Familial Mediterranean fever carriers.

  • Familial Mediterranean fever
    Autoinflammatory
    AR
  • Familial Mediterranean fever (AD forms)
    Autoinflammatory
    AD
    Dedicated page coming soon
  • Familial Mediterranean fever carrier
    Autoinflammatory
    AR carrier
    Dedicated page coming soon

Inheritance pattern

Conditions caused by pathogenic MEFV variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous MEFV carrier status across ancestry groups?

UK clinical status

In the UK, the MEFV gene is recognised on several NHS Genomic Medicine Service national panels. These include panels for Autoinflammatory disorders, COVID-19 research, Gastrointestinal epithelial barrier disorders, Infantile enterocolitis & monogenic inflammatory bowel disease, Periodic fever syndromes, and Primary immunodeficiency or monogenic inflammatory bowel disease.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Autoinflammatory disorders · R413 NHS GMS → Primary immunodeficiency or monogenic inflammatory bowel disease · R15 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main function of the MEFV gene?

The MEFV gene provides instructions for the pyrin protein, which is essential for regulating the body's inflammatory response. Pyrin helps to control the duration and intensity of inflammation, preventing damage to healthy tissues.

What condition is primarily associated with MEFV gene variants?

The primary condition associated with pathogenic variants in the MEFV gene is Familial Mediterranean fever, an inherited inflammatory disorder.

How is Familial Mediterranean fever inherited?

Familial Mediterranean fever is typically inherited in an autosomal recessive pattern, meaning an individual needs to inherit two copies of a pathogenic variant, one from each parent, to develop the condition. Some rare forms can be autosomal dominant.

References

  1. Milhavet F, Cuisset L, Hoffman HM. The infevers autoinflammatory mutation online registry: update with new genes and functions. Human mutation. 2008. PMID: 18409191
  2. Mikula M, Buller A, Sun W. Prevalence of known mutations in the familial Mediterranean fever gene (MEFV) in various carrier screening populations. Genetics in medicine : official journal of the American College of Medical Genetics. 2008. PMID: 18496034
  3. Ross JJ. Goats, germs, and fever: Are the pyrin mutations responsible for familial Mediterranean fever protective against Brucellosis? Medical hypotheses. 2007. PMID: 17005326
  4. Papin S, Cuenin S, Agostini L. The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing. Cell death and differentiation. 2007. PMID: 17431422
  5. Yepiskoposyan L, Harutyunyan A. Population genetics of familial Mediterranean fever: a review. European journal of human genetics : EJHG. 2007. PMID: 17568393
  6. Yu JW, Fernandes-Alnemri T, Datta P. Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Molecular cell. 2007. PMID: 17964261
  7. Rabinovitch E, Harats D, Yaron P. Familial Mediterranean fever gene and protection against asthma. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2007. PMID: 18219832
  8. Chae JJ, Wood G, Masters SL. The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production. Proceedings of the National Academy of Sciences of the United States of America. 2006. PMID: 16785446
  9. Delibaş A, Oner A, Balci B. Genetic risk factors of amyloidogenesis in familial Mediterranean fever. American journal of nephrology. 2005. PMID: 16118480
  10. Medlej-Hashim M, Delague V, Chouery E. Amyloidosis in familial Mediterranean fever patients: correlation with MEFV genotype and SAA1 and MICA polymorphisms effects. BMC medical genetics. 2004. PMID: 15018633
  11. Gershoni-Baruch R, Brik R, Zacks N. The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever. Arthritis and rheumatism. 2003. PMID: 12687559
  12. Bakkaloglu A. Familial Mediterranean fever. Pediatric nephrology (Berlin, Germany). 2003. PMID: 12836090
  13. Notarnicola C, Didelot MN, Koné-Paut I. Reduced MEFV messenger RNA expression in patients with familial Mediterranean fever. Arthritis and rheumatism. 2002. PMID: 12384939
  14. Mansfield E, Chae JJ, Komarow HD. The familial Mediterranean fever protein, pyrin, associates with microtubules and colocalizes with actin filaments. Blood. 2001. PMID: 11468188
  15. Stoffman N, Magal N, Shohat T. Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups. European journal of human genetics : EJHG. 2000. PMID: 10854115
  16. Telatar M, Grody WW. Molecular genetic testing for familial Mediterranean fever. Molecular genetics and metabolism. 2000. PMID: 11001819
  17. Aksentijevich I, Torosyan Y, Samuels J. 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. American journal of human genetics. 1999. PMID: 10090880
⚠ Draft content. This page has been flagged for manual clinical review and may contain gaps or inaccuracies. Speak with a qualified healthcare professional before acting on any information here.
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 16 August 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .