Pyrin (MEFV)
Inflammasome sensor protein (mutated in FMF)
- Expression
- Gain-of-function mutations
- Evidence level
- established
- Targeted by
- Colchicine (indirect)
Role in pathogenesis
Pyrin is encoded by the MEFV gene and acts as an intracellular 'guard' sensor for RhoA GTPase activity. In healthy cells, pyrin is kept inactive by PKN1/PKN2-mediated phosphorylation and 14-3-3 protein binding. FMF mutations in the B30.2 domain impair this regulation, allowing pyrin inflammasome assembly upon dephosphorylation alone. This is the root cause of FMF.
Targeting drugs (1)
| Drug | Mechanism | Response | Line |
|---|---|---|---|
| Colchicine | Microtubule disruption; reduces leukocyte motility and phagocytosis | ~95% (attack prevention) | 1st |
Sources (4)
DetailsChae JJ et al. (2011) Gain-of-function Pyrin mutations induce NLRP3 protein-independent interleukin-1beta activation and severe autoinflammation in mice · ImmunityDOI ↗