Familial Mediterranean fever: genes and variants
Familial Mediterranean fever is linked to 5 analyzed proteins (MEFV, IL1B, TUBA1A, TUBB2B and TUBB3). 6 DNA variants are known to cause it; 424 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Familial Mediterranean fever, autosomal dominant
Genes linked to Familial Mediterranean fever
MEFV: Pyrin
Its pyrin inflammasome senses disruptions of cytoskeletal regulation and can activate IL-1beta-dependent inflammation. Pathogenic variants cause familial Mediterranean fever, with recurrent attacks of fever and serosal or joint inflammation.
6 disease-causing and 423 uncertain variants in MEFV are linked to Familial Mediterranean fever.
IL1B: Interleukin-1 beta
After inflammasome-mediated processing, it drives fever, leukocyte recruitment, and local inflammatory responses to infection or tissue damage. Excess production contributes to multiple autoinflammatory diseases and can be therapeutically suppressed by blocking IL-1 signaling.
0 disease-causing and 0 uncertain variants in IL1B are linked to Familial Mediterranean fever.
TUBA1A: Tubulin alpha-1A chain
An alpha-tubulin chain that pairs with beta-tubulin to build microtubules. Microtubules provide tracks for transport and help shape dividing and migrating cells, making TUBA1A especially important for fetal brain development.
0 disease-causing and 0 uncertain variants in TUBA1A are linked to Familial Mediterranean fever.
TUBB2B: Tubulin beta-2B chain
It contributes to neuronal microtubules needed for progenitor division, neuronal migration, axon development, and cortical organization. Heterozygous pathogenic variants cause tubulinopathy with polymicrogyria, cortical dysplasia, developmental delay, and sometimes epilepsy.
0 disease-causing and 0 uncertain variants in TUBB2B are linked to Familial Mediterranean fever.
TUBB3: Tubulin beta-3 chain
It forms neuronal microtubules required for axon growth, guidance, and intracellular transport. Heterozygous pathogenic variants can cause congenital fibrosis of the extraocular muscles type 3 and broader tubulinopathy phenotypes with brain and cranial-nerve abnormalities.
0 disease-causing and 0 uncertain variants in TUBB3 are linked to Familial Mediterranean fever.
Weakly linked (only a few uncertain records): MPL.
Where Familial Mediterranean fever variants cluster
- MEFV B30.2/SPRY (positions 580–775): 3 of 6 disease-causing changes, 2.0× more than its size predicts.
Known disease-causing variants in Familial Mediterranean fever
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| MEFV S242R | 242 | Disease-causing (★★) | |
| MEFV E167D | 167 | Disease-causing (★★) | |
| MEFV F479L | 479 | Required for homotrimerization and induction of | Disease-causing (★★) |
| MEFV M680I | 680 | B30.2/SPRY | Disease-causing (★★) |
| MEFV V726A | 726 | B30.2/SPRY | Disease-causing (★★) |
| MEFV R761H | 761 | B30.2/SPRY | Disease-causing (★★) |
Diseases related to Familial Mediterranean fever
- Non-small cell lung carcinoma, also linked to TUBA1A, TUBB2B and TUBB3
- Prostate cancer, also linked to TUBA1A, TUBB2B and TUBB3
- Cervical cancer, also linked to TUBA1A, TUBB2B and TUBB3
- Tubulinopathy, also linked to TUBA1A and TUBB2B
- Complex cortical dysplasia with other brain malformations 7, also linked to TUBB2B and TUBB3
- Ovarian cancer, also linked to TUBB2B and TUBB3
- Myocardial infarction, also linked to TUBB2B and TUBB3
- Autosomal recessive limb-girdle muscular dystrophy, also linked to TUBA1A
- Lissencephaly due to TUBA1A mutation, also linked to TUBA1A
- Gastric cancer, also linked to TUBA1A
- Cryopyrin associated periodic syndrome, also linked to IL1B
- Autoinflammatory syndrome, also linked to MEFV
Frequently asked questions
Which genes are linked to Familial Mediterranean fever?
In CATVariant, Familial Mediterranean fever is linked to 5 analyzed proteins: MEFV (Pyrin), IL1B (Interleukin-1 beta), TUBA1A (Tubulin alpha-1A chain), TUBB2B (Tubulin beta-2B chain) and TUBB3 (Tubulin beta-3 chain).
How many genetic variants are linked to Familial Mediterranean fever?
479 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 424 are of uncertain significance or have conflicting reports.
Which uncertain variants in Familial Mediterranean fever look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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