Molecule

TNFR1 (TNFRSF1A)

Mutated receptor — primary disease gene product

Expression change
Misfolded / ER-retained
Evidence level
established

Role in pathogenesis

TNFR1 is the 55 kDa type 1 TNF receptor encoded by TNFRSF1A. In TRAPS, missense mutations in the extracellular cysteine-rich domains cause protein misfolding, ER retention, and abnormal disulfide-linked oligomerisation. The mutant receptor does not function normally on the cell surface but instead potentiates inflammation from within the ER.

Sources (3)

DetailsMcDermott MF et al. (1999) Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromesDOI
DetailsLobito AA et al. (2006) Abnormal disulfide-linked oligomerization results in ER retention and altered signaling by TNFR1 mutants in TRAPSDOI
DetailsSimon A et al. (2010) Concerted action of wild-type and mutant TNF receptors enhances inflammation in TNF receptor 1-associated periodic fever syndromeDOI