Familial hemophagocytic lymphohistiocytosis (FHPL), including the following three diseases:
Perforin deficiency;
Munc deficiency;
STX11 deficiency

Familial hemophagocytic lymphohistiocytosis is an autosomal recessive disorder with uncontrolled activation of T cells and macrophages (hemophagocytic activation) that infiltrate into liver, spleen, bone marrow, and CNS. The symptoms include fever, hepatosplenomegaly, and cytopenia. Homozygous and heterozygous gene mutations of perforin, the major immune cytotoxic protein, were detected with frequency between 15% and 50% of all FHPL patients. UNC13D is the second gene associated with FHPL. The encoded protein (Munc13-4) is important for cytolytic granule exocytosis. Recently a third FHPL associated gene on chromosome 6q24 with mutations in STX11 was identified. The encoded protein, t-SNARE syntaxin 11, also plays a role in intracellular trafficking, but its precise role is not known.

Primary immunodeficiency

PRF1 [HSA:5551] [KO:K07818]
UNC13D [HSA:201294]
STX11 [HSA:8676] [KO:K08487]

PMID:16304363 (description, gene)

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PMID:17162365 (gene)

Kumar A, Teuber SS, Gershwin ME.

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PMID:15096561 (gene)

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PMID:18424339 (gene)

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PMID:17952897 (gene)

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J Allergy Clin Immunol 120:776-94 (2007)