MEFV Gene - Pyrin (Marenostrin)
Key regulator of innate immunity and inflammasome activation; associated with familial Mediterranean fever
Gene Information Card
| Symbol | MEFV |
|---|---|
| Full Name | MEFV innate immunity regulator, pyrin |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 4210 ncbi.nlm.nih.gov/gene/4210 |
| Ensembl ID | ENSG00000103313 |
| UniProt ID | O15553 |
| OMIM ID | 608107 |
| HGNC ID | 6998 |
| Aliases | FMF, TRIM20, pyrin, marenostrin |
Description
The MEFV gene encodes pyrin (also known as marenostrin), a protein primarily expressed in myeloid cells. Pyrin is a key component of the innate immune system, functioning as a pattern recognition receptor that assembles an inflammasome complex in response to bacterial modifications of Rho GTPases. Mutations in MEFV are the primary cause of familial Mediterranean fever (FMF), an autosomal recessive autoinflammatory disorder characterized by recurrent episodes of fever and serositis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial Mediterranean fever (FMF) | Gain-of-function mutations in MEFV lead to constitutive or hyperactive pyrin inflammasome assembly, resulting in excessive IL-1β production and systemic inflammation. | ClinVar, OMIM |
| Behçet disease (susceptibility) | Certain MEFV variants (e.g., M694V) increase risk for Behçet disease, possibly through enhanced inflammasome activation. | NCBI Gene, OMIM |
| Inflammatory bowel disease (susceptibility) | MEFV polymorphisms have been associated with Crohn disease and ulcerative colitis, likely via altered pyrin-mediated immune responses. | NCBI Gene, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 8.3 | Medium |
| Lung | 4.1 | Low |
| Whole blood | 3.9 | Low |
| Small intestine | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression; used for inflammasome studies |
| HL-60 (promyeloblast) | 10.1 | Medium expression |
| K-562 (lymphoblast) | 6.5 | Low expression |
| HeLa (cervical) | 1.2 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| M694V | Missense | ~30% of FMF alleles (Mediterranean populations) | Gain-of-function; increased pyrin inflammasome activity |
| V726A | Missense | ~15% of FMF alleles | Gain-of-function; milder phenotype |
| M680I | Missense | ~10% of FMF alleles | Gain-of-function; moderate severity |
| E148Q | Missense | ~5% of FMF alleles | Likely benign polymorphism; may modify disease expression |
Mutation functional classification
Loss of Function (LOF)
Not reported; all known pathogenic MEFV mutations are gain-of-function.
Gain of Function (GOF)
Yes. Most FMF-associated mutations (e.g., M694V, V726A, M680I) enhance pyrin inflammasome assembly and IL-1β release.
Dominant Negative (DN)
Not described for MEFV.
View complete mutation data：
Gene Ontology (GO)
| • GO:0002218 ~ activation of innate immune response | • GO:0005515 ~ protein binding |
| • GO:0045087 ~ innate immune response | • GO:0061702 ~ inflammasome complex |
| • GO:0072559 ~ NLRP3 inflammasome complex assembly | • GO:0005737 ~ cytoplasm |
Pathways
• Pyrin inflammasome pathway (Reactome: R-HSA-844456)
• Interleukin-1 family signaling (Reactome: R-HSA-446652)
• Innate immune system (Reactome: R-HSA-168249)
Protein Summary
Pyrin (UniProt O15553) is a 781-amino-acid protein containing an N-terminal PYRIN domain, a B-box zinc finger, a coiled-coil region, and a C-terminal B30.2/SPRY domain. It functions as a scaffold for inflammasome assembly upon sensing bacterial Rho GTPase modifications (e.g., by Clostridium difficile toxin B). The B30.2 domain is the hotspot for FMF mutations. Pyrin interacts with ASC and pro-caspase-1 to form an active inflammasome, leading to IL-1β maturation and pyroptosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MEFV Knockout HEK293 Cell Line | EDJ-KQ5196 | Human | 4210 | Details Get a Quote |
| MEFV Knockout HeLa Cell Line | EDJ-KQ53860 | Human | 4210 | Details Get a Quote |
| MEFV Knockout A-549 Cell Line | EDJ-KQ62348 | Human | 4210 | Details Get a Quote |
| MEFV Knockout HCT 116 Cell Line | EDJ-KQ70818 | Human | 4210 | Details Get a Quote |
| Mefv Knockout IBMDM Cell Line | EDC07959 | Mouse | 54483 | Details Get a Quote |
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