Table 2.

Primary Hemophagocytic Lymphohistiocytosis and Kawasaki Disease-Associated Genes.

Phenotype	Gene name	Gene product's putatuve function, mendelian disorder association (NCBI Gene, OMIM)
Primary hemophagocytic lymphohistiocytosis
Familial HLH	PRF1	Forms membrane pores that allow the release of granzymes and subsequent cytolysis of target cells. Hemophagocytic lymphohistiocytosis, familial, 2.
	STX11	Implicated in the targeting and fusion of intracellular transport vesicles. Hemophagocytic lymphohistiocytosis, familial, 4.
	STXBP2	Involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Hemophagocytic lymphohistiocytosis, familial, 5.
	UNC13D	Appears to play a role in vesicle maturation during exocytosis and is involved in regulation of cytolytic granules secretion. Hemophagocytic lymphohistiocytosis, familial, 3.
Primary Immunodeficiencies associated with HLH	AP3B1	May play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. Hermansky-Pudlak syndrome 2.
	BIRC4	Functions through binding to TNF receptor-associated factors TRAF1 and TRAF2 and inhibits apoptosis induced by menadione, a potent inducer of free radicals, and interleukin 1-beta converting enzyme. Also inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. X-linked lymphoproliferative syndrome.
	CD27	Required for generation and maintenance of T cell immunity. Binds ligand CD70, plays key role in regulating B-cell activation and immunoglobulin synthesis. Transduces signals that lead to the activation of NF-kappaB and MAPK8/JNK. Lymphoproliferative syndrome 2.
	ITK	Encodes an intracellular tyrosine kinase expressed in T-cells. Lymphoproliferative syndrome 1.
	LYST	regulates intracellular protein trafficking in endosomes, and may be involved in pigmentation. Chediak-Higashi syndrome.
	RAB27A	May be involved in protein transport and small GTPase mediated signal transduction. Griscelli syndrome type 2.
	SH2D1A	Plays a major role in the bidirectional stimulation of T and B cells. Lymphoproliferative syndrome, X-linked 1, or Duncan disease.
Kawasaki disease
Development of KD	ABCC4	Member of the superfamily of ATP-binding cassette (ABC) transporters, MRP subfamily involved in multi-drug resistance. Plays a role in cellular detoxification as a pump for its substrate, organic anions. May also function in prostaglandin-mediated cAMP signaling in ciliogenesis.
	CD40	Part of TNF-receptor superfamily. Receptor on antigen-presenting cells, essential for mediating variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. Hyper-IgM immunodeficiency, type 3.
	FCGR2A	Immunoglobulin Fc receptor gene, found on the surface of many immune response cells. Cell surface receptor found on phagocytic cells such as macrophages and neutrophils, involved in the process of phagocytosis and clearing of immune complexes.
	TLR6	Plays a role in pathogen recognition and activation of innate immunity. Recognizes pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity.
Resistance to IVIG +/- CAD development in KD	ITPKC	Encodes a member of the inositol 1,4,5-trisphosphate [Ins(1, 4, 5)P(3)] 3-kinase family of enzymes that catalyze the phosphorylation of inositol 1,4,5-trisphosphate to 1,3,4,5-tetrakisphosphate+/NFAT pathway
	CASP3	Cysteine-aspartic acid protease that plays a central role in the execution-phase of cell apoptosis
	ORAI1	Membrane calcium channel subunit that is activated by the calcium sensor STIM1 when calcium stores are depleted. Primary way for calcium influx into T-cells. Immune dysfunction with T-cell inactivation due to calcium entry defect, type 1.