MEFV

Chr 16ADAR

MEFV innate immunity regulator, pyrin

Also known as: FMF, MEF, PAAND, TRIM20

The protein pyrin regulates innate immunity and inflammatory responses by serving as an inflammasome component and autophagy receptor that controls IL1B and IL18 production. Mutations cause familial Mediterranean fever, a hereditary periodic fever syndrome, and acute febrile neutrophilic dermatosis, with both autosomal dominant and autosomal recessive inheritance patterns described. The gene shows low constraint against loss-of-function variants (LOEUF 1.129), suggesting tolerance to such changes.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 1.133 OMIM phenotypes
Clinical SummaryMEFV
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Gene-Disease Validity (ClinGen)
familial Mediterranean fever · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 0.99
OE 0.81 (0.591.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.72Z-score
OE missense 1.23 (1.141.32)
551 obs / 448.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.81 (0.591.13)
00.351.4
Missense OE1.23 (1.141.32)
00.61.4
Synonymous OE1.23
01.21.6
LoF obs/exp: 25 / 30.9Missense obs/exp: 551 / 448.7Syn Z: -2.50
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMEFV-related familial mediterranean feverLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7131th %ile
GOF
0.73top 25%
LOF
0.2483th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

GOFIn 2016 specific heterozygous gain-of-function mutations in the Mediterranean fever gene MEFV were reported as causal for a distinct autoinflammatory disease coined pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND).PMID:33693560

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MEFV · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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