Hemophagocytic Lymphohistiocytosis malady

NIH Rare Diseases: Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal condition in which certain white blood cells (histiocytes and lymphocytes) build up in organs including the skin, spleen, and liver, and destroy other blood cells. This causes fever and damages the liver and spleen, resulting in enlargement of these organs. HLH may be inherited or it may be caused by certain conditions or diseases including infections and immunodeficiency (inability of the body to fight infections). It most commonly affects young infants and children. Treatment includes antibiotics or antiviral medications to treat or prevent infections, and chemotherapy and immunotherapy prior to allogeneic hematopoietic cell transplantation.³⁰

MalaCards: Hemophagocytic Lymphohistiocytosis, also known as familial hemophagocytic lymphohistiocytosis, is related to albinism and griscelli syndrome type 2. An important gene associated with Hemophagocytic Lymphohistiocytosis is UNC13D (unc-13 homolog D (C. elegans)), and among its related pathways are Graft-versus-host disease and Immune response_CD16 signaling in NK cells. The compounds ivig and ionomycin have been mentioned in the context of this disorder. Affiliated tissues include spleen, liver and skin, and related mouse phenotypes are craniofacial and pigmentation.

Disease Ontology: A lymphatic system disease that is characterized by an expansion of the monocyte-macrophage population and intense hemophagocytosis. it can occur de novo, but more often occurs in the setting of another disorder, usually an infection or a malignancy. a clinical picture of fever, hepatosplenomegaly, lymphadenopathy and peripheral pancytopenia. the morphologic hallmark of this syndrome is the phagocytosis of hematopoietic elements by morphologically normal macrophages.⁶

Genetics Home Reference: Familial hemophagocytic lymphohistiocytosis is a disorder in which the immune system produces too many activated immune cells (lymphocytes) called T cells, natural killer cells, B cells, and macrophages (histiocytes). Excessive amounts of immune system proteins called cytokines are also produced. This over-activation of the immune system causes fever and damages the liver and spleen, resulting in enlargement of these organs.¹⁷

Wikipedia: Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is an uncommon...⁴⁴ more...

GeneReviews summary for hlh

Aliases & Descriptions:

hemophagocytic lymphohistiocytosis 6 7 30 8 familial hemophagocytic lymphohistiocytosis 30 16 17 32 hemophagocytic lymphohistiocytosis familial -1 30 16 familial erythrophagocytic lymphohistiocytosis 30 16 hemophagocytic syndrome 6 17 hemophagocytic lymphohistiocytosis, familial, 1 33 primary hemophagocytic hymphohistiocytosis 17 lymphohistiocytosis, hemophagocytic 43 haemophagocytic lymphohistiocytosis 6 lymphohistiocytosis hemophagocytic 32

familial histiocytic reticulosis 30 haemophagocytic syndrome 6 lymphohistiocytosis 43 hplh1 30 hplh 17 fhl1 16 fhlh 16 hps 6 fhl 17 fel 17

Diseases related to hemophagocytic lymphohistiocytosis by text searches and GeneDecks gene sharing:

(show top 50)    (show all 696)

id	Related Disease	Score	Top Affiliating Genes
1	albinism	30.9	RAB27A, MLPH, AP3B1, IFNG, F2, GK
2	griscelli syndrome type 2	30.9	RAB27A, UNC13D, MLPH, CCL5
3	b-cell lymphomas	30.5	XIAP, GZMB, IL16, FAS, PTPN6, TIA1
4	griscelli syndrome	30.5	MYO5A, RAB27A, UNC13D, MLPH, CCL5
5	peripheral t-cell lymphoma	30.2	NCAM1, GZMB, IL2RA, TIA1
6	acute liver failure	30.1	GPT, F2, SLC17A5
7	hermansky-pudlak syndrome	29.9	RAB27A, LAMP1, AP3B1, CCL2, CSF3, LYST
8	polyradiculoneuropathy	29.8	IL2, IFNG, PRF1
9	hepatitis	29.5	GZMB, FAS, GPT, F2, SLC17A5
10	miliary tuberculosis	29.3	IL18, ENO2, IFNG, CSF3
11	agammaglobulinemia	29.3	SH2D1A, IL2, IL2RA, TNF, STX11
12	pure red-cell aplasia	29.1	GZMB, IL2, IL2RA, F2
13	aplastic anemia	28.7	SH2D1A, GZMB, FAS, IFNG, CSF2, CSF3
14	chediak-higashi syndrome	28.7	SH2D1A, RAB27A, UNC13D, LAMP1, AP3B1, STX11
15	lyme disease	28.2	ENO2, CCL4, IFNG, TNF
16	polycythemia	28.2	FTH1, FTL, FAS, F2, PTPN6, TYK2
17	pulmonary tuberculosis	28.1	IL18, IL2, IL2RA, CCL4, IFNG
18	piebaldism	28.0	MYO5A, RAB27A, MLPH
19	peripheral arterial occlusive disease	28.0	IL18, CCL2, GPT, F2
20	extrinsic allergic alveolitis	27.9	IL2RA, IL8, CCL2, CCL5
21	arterial occlusive disease	27.9	IL18, CCL2, GPT, F2
22	liver cancer	27.8	XIAP, FHL2, IL2, FAS, CCL5, GPT
23	fatty liver disease	27.6	FTH1, FTL, GPT, TNF, AHSG, SLC17A5
24	cholecystitis	27.5	IL2RA, GPT, F2, TNF
25	head injury	27.2	IL18, IL8, ENO2, F2
26	chronic granulomatous disease	27.1	IL8, GPT, IFNG, TNF, CYCS, STX11
27	hepatitis b	27.1	IL18, IL2RA, GPT, IFNG, F2, SLC17A5
28	systemic lupus erythematosus, association with	27.0	IL16, IL18, IFNG, TNF, CSF3
29	hemochromatosis	26.8	FTH1, FTL, CCL2, GPT, F2, TNF
30	acquired immunodeficiency syndrome	26.8	NCAM1, IL16, IL2, CCL4, CCL5, GNLY
31	myopathy	26.8	NCAM1, XIAP, GZMB, IL8, FAS, CCL4
32	retinopathy of prematurity	26.8	IL18, IL2, TNF, CSF2, CSF3
33	sepsis	26.7	IL18, IL8, CCL4, CCL2, F2, TNF
34	immunodeficiency	26.7	GZMB, IL18, IL2, IL2RA, FAS, IFNG
35	autoimmune hemolytic anemia	26.7	IL2, IL2RA, IFNG, TNF
36	periodontitis	26.5	IL16, IL8, CCL2, TNF, SLC17A5
37	pancytopenia	26.4	SH2D1A, RAB27A, XIAP, IL2RA, IFNG, CSF2
38	splenomegaly	26.4	IL2RA, FAS, ENO2, GPT, SMPD1, CSF3
39	hypothyroidism	26.4	FTH1, FTL, IL2, IL2RA, GPT, F2
40	headache	26.3	IL2, IL2RA, CCL2, IFNG, TNF
41	rheumatic fever	26.2	IL2, IL2RA, IL8, TNF
42	adult-onset still's disease	26.2	IL18, IL2RA, IL8, FAS, CCL2, TNF
43	rheumatoid arthritis, association with	26.2	IL18, IL8, GPT, IFNG, TNF, CSF3
44	polymyalgia rheumatica	26.1	IL2, IL2RA, CCL2, CCL5, IFNG, TNF
45	gestational diabetes	26.1	IL18, IL8, FAS, CCL2, TNF, AHSG
46	sleep apnea	26.1	IL18, IL8, CCL2, GPT, TNF, SLC17A5
47	morbid obesity	25.9	IL18, CCL2, GPT, IFNG, F2, TNF
48	acne	25.9	GZMB, IL18, IL8, CCL2, IFNG, TNF
49	apnea	25.9	IL18, IL8, ENO2, CCL2, GPT, TNF
50	ischemic heart disease	25.7	IL8, CCL2, F2, TNF, CYCS, CSF3

Approved drugs:

Drug clinical trials:

MalaCards organs/tissues related to hemophagocytic lymphohistiocytosis:

²²

MGI Mouse Phenotypes related to hemophagocytic lymphohistiocytosis:

²⁵ (show all 15)

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	craniofacial phenotype	MP:0005382	9.4	LYST, CSF2, AP3B1, LAMP1, MYO5A
2	pigmentation phenotype	MP:0001186	8.9	LYST, PTPN6, CCL2, FAS, AP3B1, MLPH
3	skeleton phenotype	MP:0005390	8.9	CSF2, TIA1, CYCS, PTPN6, TP63, FAS
4	hematopoietic system phenotype	MP:0005397	8.5	SLAMF1, SH2D1A, RAB27A, UNC13D, XIAP, FTH1
5	reproductive system phenotype	MP:0005389	7.3	CSF2, SMPD1, PTPN6, TNF, TP63, IFNG
6	growth/size phenotype	MP:0005378	7.1	CYCS, SMPD1, AHSG, TIA1, CSF2, LYST
7	homeostasis/metabolism phenotype	MP:0005376	6.9	TP63, PTPN6, SMPD1, AHSG, TYK2, PRF1
8	tumorigenesis	MP:0002006	6.8	CSF2, PRF1, TNF, TP63, IFNG, CCL2
9	vision/eye phenotype	MP:0005391	6.4	CCL2, IFNG, TP63, TNF, SLC17A5, LYST
10	behavior/neurological phenotype	MP:0005386	6.4	GK, CYCS, SMPD1, PRF1, CSF2, SLC17A5
11	nervous system phenotype	MP:0003631	6.0	F2, GK, TNF, PTPN6, CYCS, SMPD1
12	immune system phenotype	MP:0005387	5.9	LYST, CSF2, TIA1, TYK2, SH2D1A, MYO5A
13	integument phenotype	MP:0010771	5.8	F2, TP63, TNF, PTPN6, CSF2, CSF3
14	cellular phenotype	MP:0005384	3.9	F2, TP63, TNF, TNFSF12, PTPN6, CYCS
15	mortality/aging	MP:0010768	3.8	CYCS, PTPN6, TNF, TP63, GK, SNAP23

Articles related to hemophagocytic lymphohistiocytosis:

(show top 50)    (show all 64)

id	Title	Authors	Year	Affiliating Genes
1	Hemophagocytic lymphohistiocytosis with Munc13-4 muta tion: a cause of recurrent fatal hydrops fetalis. (21646258)	Bechara E.... PondarrAc C.	2011	UNC13D
2	Clinical analysis and follow-up study of Epstein-Bar r virus associated-hemophagocytic lymphohistiocytosis in childhood (20426937)	Lu G.... Liu C.Y.	2010	FHL2
3	Novel syntaxin 11 gene (STX11) mutation in three Arge ntinean patients with hemophagocytic lymphohistiocytosis. (19967551)	Danielian S.... Braier J.	2010	STX11
4	Preliminary clinical analysis of the hepatic dysfunc tion in patients with acquired hemophagocytic lymphohistiocytosis (19840483)	Yang L.Z.... Wang Z.	2009	SLC17A5
5	The early diagnosis and clinical analysis of 57 case s of acquired hemophagocytic lymphohistiocytosis (19576122)	Wang Z.... Chen X.	2009	IL2RA
6	Fatal hemophagocytic lymphohistiocytosis in X-linked chronic granulomatous disease associated with a perforin gene variant. (19058215)	van Montfrans J.M.... Boelens J.J.	2009	PRF1, STX11
7	Familial hemophagocytic lymphohistiocytosis type 5 (F HL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11. (19804848)	Zur Stadt U.... Hennies H.C.	2009	STXBP2, STX11
8	Secondary hemophagocytic lymphohistiocytosis and severe sepsis/ systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. (19325510)	Castillo L.... Carcillo J.	2009	IL2RA
9	Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis. (18710388)	Horne A.... Henter J.I.	2008	PRF1, UNC13D, STX11
10	Central nervous system involvement in Turkish children with primary hemophagocytic lymphohistiocytosis. (18984839)	Gurgey A.... Gumruk F.	2008	GPT
11	Fatal sibling cases of familial hemophagocytic lymphohistiocytosis (FHL) with MUNC13-4 mutations: case reports. (18432499)	Nakao T.... Matsui A.	2008	UNC13D
12	Sequence analysis of the SRGN, AP3B1, ARF6, and SH2D1A genes in familial hemophagocytic lymphohistiocytosis. (18000860)	Ma D.... Zheng C.	2008	SH2D1A, ARF6, AP3B1
13	Soluble TWEAK is markedly elevated in hemophagocytic lymphohistiocytosis. (17918252)	Nagasawa M.... Mizutani S.	2008	TNFSF12
14	Mutations affecting mRNA splicing are the most common molecular defect in patients with familial hemophagocytic lymphohistiocytosis type 3. (18492689)	Santoro A.... Arico M.	2008	UNC13D
15	Hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis: a retrospective analysis of data from the Italian Association of Pediatric Hematology Oncology (AIEOP). (18768529)	Cesaro S.... Fagioli F.	2008	FHL2
16	Genetic loci contributing to hemophagocytic lymphohistiocytosis do not confer susceptibility to systemic-onset juvenile idiopathic arthritis. (18311812)	Donn R.... Ramanan A.V.	2008	GZMB, PRF1, RAB27A
17	A Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH). (18991284)	Pachlopnik Schmid J.... de Saint Basile G.	2008	CCL5, RAB27A
18	Acute liver failure in a child with Epstein-Barr virus infection and undiagnosed glycerol kinase deficiency, mimicking hemophagocytic lymphohistiocytosis. (18607276)	Nordenstrom A.... von Dobeln U.	2008	GK
19	Clinical and molecular aspects of Turkish familial hemophagocytic lymphohistiocytosis patients with perforin mutations. (18190960)	Okur H.... Gurgey A.	2008	PRF1
20	Familial hemophagocytic lymphohistiocytosis in two brothers with X-linked agammaglobulinemia. (18421721)	Schultz K.A.... Kumar A.	2008	STX11
21	Neonatal primary hemophagocytic lymphohistiocytosis in Turkish children. (19131769)	Gurgey A.... Yurdakok M.	2008	UNC13D
22	Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients. (17525286)	Bryceson Y.T.... Ljunggren H.G.	2007	FHL2, UNC13D, STX11
23	Novel spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis in ethnic Omani patients. (17674359)	Muralitharan S.... Krishnamoorthy R.	2007	PRF1, FHL2
24	Perforin gene mutations in adult-onset hemophagocytic lymphohistiocytosis. (17606450)	Nagafuji K.... Harada M.	2007	PRF1
25	Serum granulysin is elevated in patients with hemophagocytic lymphohistiocytosis. (18192122)	Nagasawa M.... Mizutani S.	2007	GNLY
26	Perforin gene analaysis in an Iranian family with familial hemophagocytic lymphohistiocytosis. (17652853)	Galehdari H.... Molavi M.A.	2007	PRF1
27	Correlation between phenotypic heterogeneity and gene mutational characteristics in familial hemophagocytic lymphohistiocytosis (FHL). (16365863)	Ueda I.... Imashuku S.	2006	FHL2, UNC13D
28	Tumor necrosis factor alpha promoter polymorphism associated with increased susceptibility to secondary hemophagocytic lymphohistiocytosis in the Korean population. (17166738)	Chang Y.H.... Cho H.I.	2006	TNF
29	Prolonged course of familial hemophagocytic lymphohistiocytosis. (17164654)	Steinberg O.... Tamary H.	2006	PRF1
30	Aberrant maturation of mutant perforin underlies the clinical diversity of hemophagocytic lymphohistiocytosis. (16374518)	Risma K.A.... Sumegi J.	2006	PRF1
31	Familial hemophagocytic lymphohistiocytosis in an adult patient homozygous for A91V in the perforin gene, with tuberculosis infection. (16956828)	Mancebo E.... Vercher F.J.	2006	PRF1
32	Hemophagocytic lymphohistiocytosis and related disorders. (17088644)	Filipovich A.H.	2006	RAB27A
33	Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type-4 to chromosome 6q24 and identification of mutations in syntaxin 11. (15703195)	Zur Stadt U.... Hennies H.C.	2005	FHL2, UNC13D, STX11
34	Review of hemophagocytic lymphohistiocytosis (HLH) in children with focus on Japanese experiences. (15718147)	Ishii E.... Yasukawa M.	2005	PRF1, FHL2, UNC13D
35	Mutations of syntaxin 11 and SNAP23 genes as causes of familial hemophagocytic lymphohistiocytosis were not found in Japanese people. (16180048)	Yamamoto K.... Yasukawa M.	2005	SNAP23, STX11
36	Genetic subtypes of familial hemophagocytic lymphohistiocytosis: correlations with clinical features and cytotoxic T lymphocyte/natural killer cell functions. (15632205)	Ishii E.... Yasukawa M.	2005	PRF1, FHL2, UNC13D
37	Herpes simplex virus 2-associated hemophagocytic lymphohistiocytosis in a pregnant patient. (15863596)	Yamaguchi K.... Murashima A.	2005	IL2RA
38	Increased IL-16 levels in hemophagocytic lymphohistiocytosis. (15342983)	Takada H.... Hara T.	2004	IL16
39	Fatal hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus infection in a patient with a novel mutation in the signaling lymphocytic activation molecule-associated protein. (14583885)	Halasa N.B.... Crowe J.E. Jr.	2003	SH2D1A
40	Peripheral T-cell lymphoma associated consecutively with hemophagocytic lymphohistiocytosis and hypereosinophilic syndrome. (12950242)	GutiAcrrez A.... RodrA-guez J.	2003	IL2, CSF2
41	Sequence analysis of the granulysin and granzyme B genes in familial hemophagocytic lymphohistiocytosis. (12483306)	Ericson K.G.... Henter J.I.	2003	GZMB, GNLY
42	Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). (14622600)	Feldmann J.... de Saint Basile G.	2003	UNC13B, UNC13D
43	Elevated sphingomyelinase and hypercytokinemia in hemophagocytic lymphohistiocytosis. (12142792)	Takahashi T.... Takada G.	2002	SMPD1
44	Interleukin-18 in hemophagocytic lymphohistiocytosis. (11699209)	Takada H.... Hara T.	2001	IL18
45	Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis. (11179007)	Goeransdotter Ericson K.... Henter J.-I.	2001	PRF1
46	Hemophagocytic lymphohistiocytosis due to germline mutations in SH2D1A, the X-linked lymphoproliferative disease gene. (11159547)	Arico M.... Nichols K.E.	2001	SH2D1A
47	Localization of a gene for familial hemophagocytic lymphohistiocytosis at chromosome 9q21.3-22 by homozygosity mapping. (9915955)	Ohadi M.... Layton D.M.	1999	HPLH1
48	Perforin gene defects in familial hemophagocytic lymphohistiocytosis. (10583959)	Stepp S.E.... Kumar V.	1999	PRF1
49	Soluble interleukin-2 receptor: a useful prognostic factor for patients with hemophagocytic lymphohistiocytosis. (8541568)	Imashuku S.... Tsunematsu Y.	1995	IL2RA
50	Eruptive fever of rare cause: familial hemophagocytic lymphohistiocytosis (7842105)	PiAcrart F.... Ninane J.	1994	F2

Genes related to hemophagocytic lymphohistiocytosis according to GeneCards:

(show top 50)    (show all 61)

id	Symbol	Description	Score	GeneCards Section Context
1	UNC13D	unc-13 homolog D (C. elegans)	11.1	Summaries, Publications
2	STX11	syntaxin 11	11.1	Summaries, Publications
3	PRF1	perforin 1 (pore forming protein)	11.1	Publications, Summaries
4	STXBP2	syntaxin binding protein 2	11.1	Publications, Summaries
5	HPLH1	hemophagocytic lymphohistiocytosis 1	11.1	Aliases & Descriptions, Publications
6	FHL2	four and a half LIM domains 2	11.0	Publications
7	SH2D1A	SH2 domain containing 1A	11.0	Publications
8	RAB27A	RAB27A, member RAS oncogene family	11.0	Publications
9	GNLY	granulysin	11.0	Publications
10	TNFSF12	tumor necrosis factor (ligand) superfamily, member 12	11.0	Publications
11	FHL3	four and a half LIM domains 3	11.0
12	SRGN	serglycin	11.0	Publications
13	RAB17	RAB17, member RAS oncogene family	11.0
14	RAB20	RAB20, member RAS oncogene family	11.0
15	RAB18	RAB18, member RAS oncogene family	11.0
16	LAMP1	lysosomal-associated membrane protein 1	11.0	Publications
17	GK	glycerol kinase	11.0	Publications
18	ARF6	ADP-ribosylation factor 6	11.0	Publications
19	SNAP23	synaptosomal-associated protein, 23kDa	11.0	Publications
20	TYK2	tyrosine kinase 2	11.0	Publications
21	SMPD1	sphingomyelin phosphodiesterase 1, acid lysosomal	11.0	Publications
22	SLAMF1	signaling lymphocytic activation molecule family member 1	11.0
23	RAB37	RAB37, member RAS oncogene family	11.0
24	FHL5	four and a half LIM domains 5	11.0
25	GZMB	granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1)	11.0	Publications
26	FTH1	ferritin, heavy polypeptide 1	11.0
27	AHSG	alpha-2-HS-glycoprotein	11.0
28	FTL	ferritin, light polypeptide	11.0
29	UNC13B	unc-13 homolog B (C. elegans)	11.0	Publications
30	PDLIM7	PDZ and LIM domain 7 (enigma)	11.0
31	PTPN6	protein tyrosine phosphatase, non-receptor type 6	11.0	Publications
32	MLPH	melanophilin	11.0
33	RAB28	RAB28, member RAS oncogene family	11.0	Disorders
34	IVL	involucrin	11.0
35	RAB6A	RAB6A, member RAS oncogene family	11.0
36	TIA1	TIA1 cytotoxic granule-associated RNA binding protein	11.0
37	CCL4	chemokine (C-C motif) ligand 4	11.0	Publications
38	ENO2	enolase 2 (gamma, neuronal)	11.0	Publications
39	IL18	interleukin 18 (interferon-gamma-inducing factor)	11.0	Publications
40	IL16	interleukin 16	11.0	Publications
41	IL2RA	interleukin 2 receptor, alpha	11.0	Publications
42	AP3B1	adaptor-related protein complex 3, beta 1 subunit	11.0	Publications
43	NUP153	nucleoporin 153kDa	11.0
44	LYST	lysosomal trafficking regulator	11.0
45	XIAP	X-linked inhibitor of apoptosis	11.0
46	CCL5	chemokine (C-C motif) ligand 5	11.0	Publications
47	CSF2	colony stimulating factor 2 (granulocyte-macrophage)	11.0	Publications
48	CYCS	cytochrome c, somatic	11.0	Publications
49	SLC17A5	solute carrier family 17 (anion/sugar transporter), member 5	11.0	Publications
50	GPT	glutamic-pyruvate transaminase (alanine aminotransferase)	11.0	Publications

Pathways related to hemophagocytic lymphohistiocytosis according to GeneDecks:

(show top 50)    (show all 65)

id	Pathway	Score	Top Affiliating Genes
1	Graft-versus-host disease20	10.3	IL2, PRF1
2	Immune response_CD16 signaling in NK cells41	10.2	ARF6, PTPN6, CSF2
3	Lymphocyte Signaling3	10.1	PTPN6, IL2RA, NCAM1, SH2D1A
4	Jak-STAT signaling pathway20	9.8	IL2, IL2RA, PTPN6, TYK2
5	IL-15 Signaling and its Primary Biological Effects in Different Immune Cell Types37	9.7	GZMB, IL2, IL2RA, CCL4, CSF2
6	NFAT Signaling and Lymphocyte Interactions36	9.7	CCL2, CCL4, IL2, IL16
7	Immune response IL-12 signaling pathway10	9.6	PRF1, TYK2, IFNG, IL2RA
8	Molecular Mechanisms of Cancer36	9.6	CYCS, TNFSF12, CCL5, IL2, IL16
9	Immune response_IL-12 signaling pathway41	9.5	IL2RA, IFNG, TYK2, PRF1
10	Regulation of eIF4 and p70S6K36	9.3	CCL5, CCL4, IL2, IL18, IL16
11	RAR-Gamma-RXR-Alpha Degradation36	9.2	CSF3, CSF2, CCL5, CCL4, IL2, IL16
12	ERK Signaling36	9.2	CSF3, TNFSF12, CCL5, IL2, IL18, IL16
13	PGC1Alpha Pathway36	9.1	CCL5, CCL4, IL8, IL2, IL18, IL16
14	Epithelial Tight Junctions36	9.1	SNAP23, TNF, RAB18, RAB27A, RAB20, RAB28
15	IL-2 Signaling and its Primary Biological Effects in Different Immune Cell Types37	8.8	TNF, FAS, IL2RA, IL2
16	Measles20	8.8	SLAMF1, TYK2, IFNG, FAS, IL2RA, IL2
17	SOCS Pathway36	8.7	TYK2, CCL5, CCL2, CCL4, IL8, IL2
18	Apoptosis Signaling Pathways37	8.6	CYCS, TNFSF12, TNF, FAS, XIAP
19	NOD-like receptor signaling pathway20	8.6	TNF, CCL5, CCL2, IL8, IL18, XIAP
20	Glucocorticoid Receptor Signaling36	8.5	CCL5, CCL2, CCL4, IL8, IL2RA, IL2
21	Th1 Differentiation37	8.5	TYK2, TNF, IFNG, IL2, IL18
22	THC Differentiation Pathway36	8.5	TNF, IFNG, IL2RA, IL2, IL18
23	TGF-Beta Pathway36	8.4	CCL5, CCL2, CCL4, IL8, IL2RA, IL2
24	Natural killer cell mediated cytotoxicity20	8.4	CSF2, PRF1, PTPN6, TNF, IFNG, FAS
25	Allograft rejection20	8.3	PRF1, TNF, IFNG, FAS, IL2, GZMB
26	Type I diabetes mellitus20	8.3	GZMB, IL2, FAS, IFNG, TNF, PRF1
27	Immune response CD16 signaling in NK cells10	8.2	CSF2, PTPN6, TNF, IFNG, IL2, ARF6
28	Cytokine Network36	8.1	TNF, IFNG, IL8, IL2, IL18, IL16
29	Rho Family GTPases36	8.1	CSF3, CSF2, TNFSF12, CCL5, CCL2, CCL4
30	Malaria20	8.0	CSF3, TNF, IFNG, CCL2, IL8, IL18
31	Akt Signaling36	8.0	IL2RA, CCL4, CCL2, CCL5, TNF, TNFSF12
32	Immune response MIF-mediated glucocorticoid regulation10	8.0	TNF, IFNG, IL8, IL2
33	Rheumatoid arthritis20	7.9	CSF2, TNF, IFNG, CCL5, CCL2, IL8
34	Immune response_MIF-mediated glucocorticoid regulation41	7.7	IFNG, IL8, IL2, TNF
35	Tec Kinases Signaling36	7.7	TNFSF12, TNF, CCL5, CCL2, CCL4, IL8
36	MAPK Family Pathway36	7.6	TNF, CCL5, CCL2, CCL4, IL8, IL2RA
37	JAK-STAT Pathway36	7.5	CCL5, IFNG, F2, TYK2, CCL2, CCL4
38	Influenza A20	7.4	TYK2, CYCS, TNF, IFNG, CCL5, CCL2
39	Chagas disease (American trypanosomiasis)20	7.4	TNF, IFNG, CCL5, CCL2, FAS, IL8
40	MIF Mediated Glucocorticoid Regulation36	7.3	CSF3, CSF2, TNFSF12, TNF, CCL5, CCL2
41	MIF Regulation of Innate Immune Cells36	7.3	TNF, TNFSF12, CSF2, CSF3, CCL5, CCL2
42	all-trans-Retinoic Acid Signaling in Brain36	7.3	TNF, TNFSF12, CSF2, CSF3, CCL5, CCL2
43	PEDF Induced Signaling36	7.3	TNF, TNFSF12, CSF2, CSF3, CCL5, CCL2
44	IL-6 Pathway36	7.3	CSF3, CSF2, TNFSF12, TNF, CCL5, CCL2
45	p38 Signaling36	7.1	CSF3, CSF2, TNFSF12, TNF, CCL5, CCL2
46	STAT3 Pathway36	7.1	TNF, TNFSF12, TYK2, CSF2, CSF3, CCL5
47	Endothelin-1 Signaling Pathway36	6.9	F2, TNF, TNFSF12, CSF2, CSF3, CCL5
48	PAK Pathway36	6.9	CSF3, CSF2, TNFSF12, TNF, CCL5, CCL2
49	Antioxidant Action of Vitamin-C36	6.9	CCL5, TNF, TNFSF12, CSF2, CSF3, CCL2
50	Cytokine-cytokine receptor interaction20	6.3	IFNG, TNF, TNFSF12, CSF2, CSF3, CCL5

Compounds related to hemophagocytic lymphohistiocytosis according to GeneDecks:

(show top 50)    (show all 173)

id	Compound	Score	Top Affiliating Genes
1	ivig32	10.5	CCL4, CSF2
2	ionomycin32	10.4	CCL4, GNLY, CSF2
3	endotoxin32	9.9	IL18, CCL4, CSF3, SLC17A5
4	pge232	9.9	IVL, CCL4, CCL5, SMPD1
5	glucose32	9.7	PTPN6, MYO5A, XIAP, AHSG, RAB27A, GZMB
6	n acetylcysteine32	9.5	SLC17A5, F2, GPT, IL18, IL2RA
7	h2o232	9.2	SLC17A5, CSF2, FTH1, FTL, IL18, CCL5
8	mip 1alpha32	8.6	IL8, CCL4, CCL2, CCL5, TNF, CSF2
9	sb 20358032 42	9.6	CYCS, TNF, IFNG, CCL5, CCL4, IVL
10	vegf32	8.5	ENO2, CSF3, IVL, NCAM1, TP63, CCL5
11	groalpha32	8.4	CCL4, CSF2, TNF, IL18, IL8, CCL5
12	cholesterol32 9 18 9	11.4	LYST, FTL, IVL, ARF6, IL18, ENO2
13	cysteine32	8.3	IVL, PTPN6, CYCS, IFNG, CCL5, CCL4
14	ifn-alpha32	8.3	IL18, TYK2, IFNG, CSF2, FAS, GPT
15	ribavirin32 34 9 9	11.2	IL18, SLC17A5, CSF3, CSF2, IFNG, GPT
16	toxin-132	8.1	CCL2, IL2, CCL4, TNF, IL8
17	tarc32	7.8	TNF, IL8, CCL4, CCL2, CCL5, IFNG
18	nitric oxide32 9 18 9	10.8	CCL5, SMPD1, PTPN6, NCAM1, GZMB, IL16
19	methotrexate32 34 42 9 9	11.7	CCL5, IVL, SLC17A5, CSF3, IL18, IL2RA
20	thalidomide32 42 9 9	10.7	XIAP, IL18, CSF2, IL2, TNF, IFNG
21	il-1232	7.7	TNF, CCL2, IL8, IFNG, IL2, IL18
22	pdtc32	7.7	TNF, CCL5, XIAP, CYCS, IFNG, CCL2
23	triptolide32	7.7	CCL5, CCL2, IFNG, TNF, IL8, CCL4
24	ccl332	7.7	CCL2, CCL4, CCL5, IL8, IL18, IFNG
25	egcg32	7.7	TNF, IVL, IL18, IL8, XIAP, CCL2
26	pentoxifylline32 9 9	9.5	IL18, IL2, IL2RA, IL8, IFNG, TNF
27	5fluorouracil32	7.5	CSF3, IVL, XIAP, IL2, IL18, IFNG
28	tacrolimus32 34 9 9	10.4	IFNG, GPT, SLC17A5, TNF, CCL5, IL2RA
29	okt332	7.3	CSF2, IL2, TNF, IL2RA, IFNG, FAS
30	cisplatin32 34 9 9	10.2	IL18, XIAP, IL2, IL2RA, FAS, SMPD1
31	neopterin32	7.2	GPT, IL8, IFNG, IL2RA, GZMB, IL18
32	pd 98,05932	7.2	TNF, FAS, CSF2, IL18, IVL, XIAP
33	il 1032	7.2	IL18, IL2, IL2RA, CSF2, TNF, IFNG
34	simvastatin32 34 42 9 18 9	12.1	IFNG, IL18, GPT, CCL5, SLC17A5, TNF
35	gm-csf32	7.1	IL2, IL8, CCL2, CCL5, TNF, IFNG
36	superoxide32 18	8.1	CSF2, SMPD1, CYCS, CSF3, SLC17A5, GZMB
37	herbimycin a32 42	7.9	TNF, IL2RA, IL8, PTPN6, IFNG, CCL2
38	prednisolone32 9 9	8.8	FAS, CCL4, GPT, IFNG, TNF, TIA1
39	lipid32	6.8	SLC17A5, ENO2, GK, SMPD1, NCAM1, RAB6A
40	calcium32 9 18 9	9.6	CCL5, CCL4, ENO2, IL18, IL16, SH2D1A
41	histamine32 18	7.6	CCL4, NCAM1, IL16, IL18, IL2, IL2RA
42	lactate32	6.6	CCL5, GPT, ENO2, FAS, IL8, IL18
43	thymidine32 18	7.4	CSF3, PTPN6, CSF2, FAS, IL2RA, IFNG
44	rantes32	6.0	TNF, GNLY, IFNG, CCL5, CSF3, GZMB
45	tyrosine32	6.0	IVL, SLC17A5, SLAMF1, CSF3, IL2, IL18
46	retinoic acid32 42 18	7.9	ENO2, PTPN6, NCAM1, TNF, TYK2, CSF2
47	cycloheximide32	5.9	CCL5, CCL2, CCL4, IFNG, TNF, CYCS
48	serine32	5.3	IVL, CCL2, IL2, IL18, IL16, GZMB
49	cyclosporin a32 42	6.2	CYCS, CCL5, CCL4, FAS, IL8, IL2RA
50	dexamethasone32 42 34 9 9	9.1	CCL5, TNF, CSF2, CSF3, CCL2, NCAM1

Cellular components related to hemophagocytic lymphohistiocytosis according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	cytolytic granule	GO:044194	10.4	STXBP2, PRF1
2	intracellular ferritin complex	GO:008043	10.0	FTH1, FTL
3	Golgi apparatus	GO:005794	9.2	STX11, SNAP23, SRGN, TP63, AP3B1, ARF6
4	external side of plasma membrane	GO:009897	8.2	SLAMF1, TNF, IFNG, FAS, LAMP1, NCAM1
5	extracellular region	GO:005576	6.2	IFNG, F2, SRGN, AHSG, PRF1, CSF2
6	extracellular space	GO:005615	5.6	IL16, CSF3, CSF2, AHSG, SMPD1, SRGN

Biological processes related to hemophagocytic lymphohistiocytosis according to GeneDecks:

(show all 18)

id	Name	GO ID	Score	Top Affiliating Genes
1	mast cell secretory granule organization	GO:033364	10.1	LYST, SRGN
2	small GTPase mediated signal transduction	GO:007264	10.0	ARF6, RAB18, RAB27A, RAB20, RAB37, RAB28
3	cellular response to interferon-gamma	GO:071346	9.8	IL18, CCL2, CCL5
4	protein transport	GO:015031	9.8	LYST, NUP153, STXBP2, SNAP23, ARF6, RAB18
5	cellular response to fibroblast growth factor stimulus	GO:044344	9.5	CCL5, CCL2, IL8
6	cellular response to tumor necrosis factor	GO:071356	9.5	IL18, IL8, CCL2, CCL5
7	defense response to virus	GO:051607	9.3	LYST, PRF1, IFNG, UNC13D
8	lipopolysaccharide-mediated signaling pathway	GO:031663	9.2	TNF, CCL5, CCL2, IL18
9	cellular response to organic cyclic compound	GO:071407	9.2	TNF, CCL5, CCL2, IL18
10	positive regulation of vitamin D biosynthetic process	GO:060557	9.0	TNF, IFNG
11	positive regulation of osteoclast differentiation	GO:045672	9.0	TNF, IFNG, CCL5
12	MAPK cascade	GO:000165	8.9	IL18, CCL2, CCL5, TNF
13	humoral immune response	GO:006959	8.9	TNF, IFNG, CCL2, SH2D1A
14	cytokine-mediated signaling pathway	GO:019221	8.7	CSF3, NUP153, TYK2, PTPN6, IFNG, CCL2
15	induction of apoptosis	GO:006917	8.7	TIA1, TNFSF12, TNF, TP63, FAS, UNC13B
16	immune response	GO:006955	8.3	CSF3, CSF2, TNFSF12, CCL4, IL8, IL2RA
17	response to drug	GO:042493	8.0	SMPD1, TNF, IFNG, CCL5, CCL2, ENO2
18	apoptotic process	GO:006915	7.3	XIAP, PRF1, TIA1, SRGN, CYCS, PTPN6

Molecular functions related to hemophagocytic lymphohistiocytosis according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	GTP binding	GO:005525	9.4	ARF6, RAB18, RAB27A, RAB20, RAB37, RAB28
2	chemokine activity	GO:008009	9.3	IL8, CCL4, CCL2, CCL5
3	cytokine activity	GO:005125	7.3	IL16, CSF3, CSF2, TNFSF12, TNF, IFNG
4	protein binding	GO:005515	4.9	PDLIM7, SNAP23, SRGN, CYCS, PTPN6, TIA1