Hemophagocytic lymphohistiocytosis caused by dominant-negative mutations in STXBP2 that inhibit SNARE-mediated membrane fusion

Key Points Monoallelic STXBP2 mutations affecting codon 65 impair lymphocyte cytotoxicity and contribute to hemophagocytic lymphohistiocytosis. Munc18-2R65Q/W mutant proteins function in a dominant-negative manner to impair membrane fusion and arrest SNARE-complex assembly.