Hemophagocytic Lymphohistiocytosis, Familial, 2 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

FHL2 MCID: HMP012 MIFTS: 47	Hemophagocytic Lymphohistiocytosis, Familial, 2 (FHL2) Categories: Blood diseases, Genetic diseases, Immune diseases, Liver diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Expand all tables

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Aliases & Classifications for Hemophagocytic Lymphohistiocytosis, Familial, 2

MalaCards integrated aliases for Hemophagocytic Lymphohistiocytosis, Familial, 2:

Name: Hemophagocytic Lymphohistiocytosis, Familial, 2 ⁵⁷ ⁷² ¹³ ⁷⁰

Familial Hemophagocytic Lymphohistiocytosis 2 ¹² ²⁹ ⁶ ¹⁵

Hplh2 ⁵⁷ ¹² ⁷²

Fhl2 ⁵⁷ ¹² ⁷²

Hlh2 ⁵⁷ ¹² ⁷²

Hemophagocytic Lymphohistiocytosis, Familial, 2, Susceptibility to ⁶

Lymphohistiocytosis, Hemophagocytic, Familial, Type 2 ³⁹

Characteristics:

OMIM®:

⁵⁷ (Updated 05-Apr-2021)

Inheritance:
autosomal recessive

HPO:

³¹

hemophagocytic lymphohistiocytosis, familial, 2:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Immune diseases Neuronal diseases Liver diseases Blood diseases

See all MalaCards categories (disease lists)

External Ids:

Disease Ontology ¹² DOID:0110922

OMIM® ⁵⁷ 603553

OMIM Phenotypic Series ⁵⁷ PS267700

MeSH ⁴⁴ D051359

MedGen ⁴¹ C1863727

UMLS ⁷⁰ C1863727

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Summaries for Hemophagocytic Lymphohistiocytosis, Familial, 2

OMIM® : ⁵⁷ Familial hemophagocytic lymphohistiocytosis-2 (FHL2) is an autosomal recessive disorder of immune dysregulation with onset in infancy or early childhood. It is characterized clinically by fever, edema, hepatosplenomegaly, and liver dysfunction. Neurologic impairment, seizures, and ataxia are frequent. Laboratory studies show pancytopenia, coagulation abnormalities, hypofibrinogenemia, and hypertriglyceridemia. There is increased production of cytokines, such as gamma-interferon (IFNG; 147570) and TNF-alpha (191160), by hyperactivation and proliferation of T cells and macrophages. Activity of cytotoxic T cells and NK cells is reduced, consistent with a defect in cellular cytotoxicity. Bone marrow, lymph nodes, spleen, and liver show features of hemophagocytosis. Chemotherapy and/or immunosuppressant therapy may result in symptomatic remission, but the disorder is fatal without bone marrow transplantation (summary by Dufourcq-Lagelouse et al., 1999, Stepp et al., 1999, and Molleran Lee et al., 2004). For a general phenotypic description and a discussion of genetic heterogeneity of FHL, see 267700. (603553) (Updated 05-Apr-2021)

MalaCards based summary : Hemophagocytic Lymphohistiocytosis, Familial, 2, also known as familial hemophagocytic lymphohistiocytosis 2, is related to cardiac rupture and hemophagocytic lymphohistiocytosis, and has symptoms including seizures, ataxia and hemiplegia. An important gene associated with Hemophagocytic Lymphohistiocytosis, Familial, 2 is PRF1 (Perforin 1), and among its related pathways/superpathways is Presenilin-Mediated Signaling. Affiliated tissues include liver, t cells and bone marrow, and related phenotypes are ataxia and splenomegaly

Disease Ontology : ¹² A hemophagocytic lymphohistiocytosis that has material basis in an autosomal recessive mutation of PRF1 on chromosome 10q22.1.

UniProtKB/Swiss-Prot : ⁷² Hemophagocytic lymphohistiocytosis, familial, 2: A rare disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia.

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Related Diseases for Hemophagocytic Lymphohistiocytosis, Familial, 2

Diseases in the Hemophagocytic Lymphohistiocytosis family:

Hemophagocytic Lymphohistiocytosis, Familial, 1	Hemophagocytic Lymphohistiocytosis, Familial, 4
Hemophagocytic Lymphohistiocytosis, Familial, 2	Hemophagocytic Lymphohistiocytosis, Familial, 3
Hemophagocytic Lymphohistiocytosis, Familial, 5	Secondary Hemophagocytic Lymphohistiocytosis
Primary Hemophagocytic Lymphohistiocytosis

Diseases related to Hemophagocytic Lymphohistiocytosis, Familial, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 99)

#	Related Disease	Score	Top Affiliating Genes
1	cardiac rupture	31.6	PRF1 FHL2
2	hemophagocytic lymphohistiocytosis	31.6	STX11 PRF1 GNLY FHL2
3	hemophagocytic lymphohistiocytosis, familial, 4	31.6	STX11 PRF1 FHL2
4	lymphoproliferative syndrome, x-linked, 2	31.5	STX11 PRF1 FHL2
5	lymphoproliferative syndrome, x-linked, 1	31.5	STX11 PRF1 FHL2
6	griscelli syndrome, type 2	31.5	STX11 PRF1 FHL2
7	griscelli syndrome	31.4	STX11 PRF1 FHL2
8	hemophagocytic lymphohistiocytosis, familial, 1	30.4	ZNF362 UNC119 SYS1 STX11 SCRT1 PRF1
9	hemophagocytic lymphohistiocytosis, familial, 3	29.6	SYS1 STX11 SCRT1 GNLY GET4 CES1
10	rhabdomyosarcoma	11.2
11	prostate cancer	11.1
12	hypertrophic cardiomyopathy	11.1
13	dilated cardiomyopathy	11.1
14	arrhythmogenic right ventricular cardiomyopathy	11.0
15	left ventricular noncompaction	11.0
16	hypertensive nephropathy	10.9
17	myopathy, x-linked, with postural muscle atrophy	10.8
18	deafness, autosomal recessive 65	10.8
19	scapuloperoneal myopathy	10.8
20	tibial muscular dystrophy	10.8
21	hermansky-pudlak syndrome	10.8
22	benign struma ovarii	10.8
23	oral tuberculosis	10.3	PRF1 GNLY
24	primary hemophagocytic lymphohistiocytosis	10.3	STX11 PRF1
25	phenytoin allergy	10.2	PRF1 GNLY
26	lymphoproliferative syndrome 1	10.1	STX11 PRF1
27	hypotrichosis, congenital, with juvenile macular dystrophy	10.1	CDH3 CDH15
28	ovarian cancer	10.1
29	ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome	10.1	CDH3 CDH15
30	saethre-chotzen syndrome	10.0	TCF3 GET4 CFAP47
31	colorectal cancer	10.0
32	osteogenic sarcoma	10.0
33	leukemia, acute myeloid	10.0
34	helix syndrome	10.0
35	leukemia	10.0
36	glioblastoma	10.0
37	spondylocostal dysostosis 3, autosomal recessive	9.9	NOTCH1 GNLY
38	fibrosis of extraocular muscles, congenital, 1	9.9
39	cervical cancer	9.9
40	renal fibrosis	9.9
41	colorectal adenocarcinoma	9.9
42	thrombosis	9.9
43	obstructive nephropathy	9.9
44	ischemia	9.9
45	ureteral obstruction	9.9
46	adenoma	9.9
47	b-cell lymphoma	9.9
48	myeloid leukemia	9.9
49	ovarian epithelial cancer	9.9
50	hereditary nonpolyposis colon cancer	9.9

Graphical network of the top 20 diseases related to Hemophagocytic Lymphohistiocytosis, Familial, 2:

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Symptoms & Phenotypes for Hemophagocytic Lymphohistiocytosis, Familial, 2

Human phenotypes related to Hemophagocytic Lymphohistiocytosis, Familial, 2:

³¹ (show all 41)

#	Description	HPO Frequency	HPO Source Accession
1	ataxia ³¹	very rare (1%)	HP:0001251
2	splenomegaly ³¹	very rare (1%)	HP:0001744
3	hepatomegaly ³¹	very rare (1%)	HP:0002240
4	increased intracranial pressure ³¹	very rare (1%)	HP:0002516
5	fever ³¹	very rare (1%)	HP:0001945
6	hypertriglyceridemia ³¹	very rare (1%)	HP:0002155
7	anemia ³¹	very rare (1%)	HP:0001903
8	elevated hepatic transaminase ³¹	very rare (1%)	HP:0002910
9	thrombocytopenia ³¹	very rare (1%)	HP:0001873
10	jaundice ³¹	very rare (1%)	HP:0000952
11	skin rash ³¹	very rare (1%)	HP:0000988
12	lymphadenopathy ³¹	very rare (1%)	HP:0002716
13	pancytopenia ³¹	very rare (1%)	HP:0001876
14	hepatosplenomegaly ³¹	very rare (1%)	HP:0001433
15	edema ³¹	very rare (1%)	HP:0000969
16	recurrent fever ³¹	very rare (1%)	HP:0001954
17	increased total bilirubin ³¹	very rare (1%)	HP:0003573
18	hemophagocytosis ³¹	very rare (1%)	HP:0012156
19	increased csf protein ³¹	very rare (1%)	HP:0002922
20	hypofibrinogenemia ³¹	very rare (1%)	HP:0011900
21	csf pleocytosis ³¹	very rare (1%)	HP:0012229
22	cns demyelination ³¹	very rare (1%)	HP:0007305
23	increased circulating ferritin concentration ³¹	very rare (1%)	HP:0003281
24	reduced natural killer cell activity ³¹	very rare (1%)	HP:0012178
25	failure to thrive ³¹		HP:0001508
26	tetraplegia ³¹		HP:0002445
27	encephalitis ³¹		HP:0002383
28	global developmental delay ³¹		HP:0001263
29	hypertonia ³¹		HP:0001276
30	irritability ³¹		HP:0000737
31	hyponatremia ³¹		HP:0002902
32	meningitis ³¹		HP:0001287
33	hypoalbuminemia ³¹		HP:0003073
34	prolonged prothrombin time ³¹		HP:0008151
35	coma ³¹		HP:0001259
36	generalized hypotonia ³¹		HP:0001290
37	leukopenia ³¹		HP:0001882
38	hemiplegia ³¹		HP:0002301
39	hypoproteinemia ³¹		HP:0003075
40	generalized edema ³¹		HP:0007430
41	seizure ³¹		HP:0001250

Symptoms via clinical synopsis from OMIM®:

⁵⁷ (Updated 05-Apr-2021)

Neurologic Central Nervous System:
seizures
ataxia
tetraplegia
encephalitis
increased intracranial pressure
more

Abdomen Spleen:
splenomegaly

Laboratory Abnormalities:
hypertriglyceridemia
hyponatremia
hypoalbuminemia
prolonged prothrombin time
hypoproteinemia
more

Skin Nails Hair Skin:
jaundice
purpuric rashes

Muscle Soft Tissue:
generalized edema

Growth Other:
failure to thrive

Abdomen Liver:
hepatomegaly

Hematology:
anemia
thrombocytopenia
leukopenia

Immunology:
lymphadenopathy
reduced natural killer cell cytotoxicity
overproduction by t lymphocytes and macrophages of cytokines, particularly interferon gamma and tumor necrosis factor alpha
activated hla dr+ t cells in peripheral blood
reduced t cell cytotoxicity
more

Head And Neck Head:
bulging fontanelle

Clinical features from OMIM®:

603553 (Updated 05-Apr-2021)

UMLS symptoms related to Hemophagocytic Lymphohistiocytosis, Familial, 2:

seizures; ataxia; hemiplegia; icterus; bulging fontanelle

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Drugs & Therapeutics for Hemophagocytic Lymphohistiocytosis, Familial, 2

Search Clinical Trials , NIH Clinical Center for Hemophagocytic Lymphohistiocytosis, Familial, 2

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Genetic Tests for Hemophagocytic Lymphohistiocytosis, Familial, 2

Genetic tests related to Hemophagocytic Lymphohistiocytosis, Familial, 2:

#	Genetic test	Affiliating Genes
1	Familial Hemophagocytic Lymphohistiocytosis 2 ²⁹	PRF1

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Anatomical Context for Hemophagocytic Lymphohistiocytosis, Familial, 2

MalaCards organs/tissues related to Hemophagocytic Lymphohistiocytosis, Familial, 2:

⁴⁰

Liver, T Cells, Bone Marrow, Spleen, Nk Cells, Prostate, Bone

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Publications for Hemophagocytic Lymphohistiocytosis, Familial, 2

Articles related to Hemophagocytic Lymphohistiocytosis, Familial, 2:

(show top 50) (show all 410)

#	Title	Authors	PMID	Year
1	Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations. ⁶ ⁶¹ ⁵⁷	Trizzino A...Histiocyte Society HLH Study group	17873118	2008
2	Hemophagocytic lymphohistiocytosis with neurological presentation: MRI findings and a nearly miss diagnosis. ⁵⁷ ⁶	Chiapparini L...Savoiardo M	21234777	2011
3	Characterisation of diverse PRF1 mutations leading to decreased natural killer cell activity in North American families with haemophagocytic lymphohistiocytosis. ⁵⁷ ⁶	Molleran Lee S...Filipovich AH	14757862	2004
4	Adult onset and atypical presentation of hemophagocytic lymphohistiocytosis in siblings carrying PRF1 mutations. ⁵⁷ ⁶	Clementi R...Arico M	12229880	2002
5	Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis. ⁵⁷ ⁶	Goransdotter Ericson K...Henter J	11179007	2001
6	Perforin gene defects in familial hemophagocytic lymphohistiocytosis. ⁶ ⁵⁷	Stepp SE...Kumar V	10583959	1999
7	Predominant Neurologic Manifestations Seen in a Patient With a Biallelic Perforin1 Mutation (PRF1; p.R225W). ⁶¹ ⁶	Madkaikar M...Patil V	27271812	2017
8	Spectrum of Atypical Clinical Presentations in Patients with Biallelic PRF1 Missense Mutations. ⁶ ⁶¹	Tesi B...Meeths M	26184781	2015
9	Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) caused by deep intronic mutation and inversion in UNC13D. ⁶ ⁶¹	Meeths M...Bryceson YT	21931115	2011
10	Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes. ⁶ ⁶¹	Nagai K...Yasukawa M	21152410	2010
11	Mutations in the perforin gene in children with hemophagocytic lymphohistiocytosis. ⁶ ⁶¹	Lu G...Yang S	20092789	2009
12	Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients. ⁶¹ ⁶	Bryceson YT...Ljunggren HG	17525286	2007
13	Late-onset cases of familial hemophagocytic lymphohistiocytosis with missense perforin gene mutations. ⁶¹ ⁶	Ueda I...Imashuku S	17266056	2007
14	Genetic subtypes of familial hemophagocytic lymphohistiocytosis: correlations with clinical features and cytotoxic T lymphocyte/natural killer cell functions. ⁶ ⁶¹	Ishii E...Yasukawa M	15632205	2005
15	Perforin defects of primary haemophagocytic lymphohistiocytosis in Japan. ⁶ ⁶¹	Suga N...Hara T	11841437	2002
16	Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis. ⁵⁷	Locatelli F...de Min C	32374962	2020
17	A three-year follow-up study evaluating clinical utility of exome sequencing and diagnostic potential of reanalysis. ⁶	Fung JLF...Chung BHY	32963807	2020
18	Neurological Abnormality Could be the First and Only Symptom of Familial Hemophagocytic Lymphohistiocytosis: Report of Two Families. ⁶	Zhao YZ...Zhang R	30539918	2018
19	Comprehensive Genetic Results for Primary Immunodeficiency Disorders in a Highly Consanguineous Population. ⁶	Al-Herz W...Notarangelo LD	30697212	2018
20	Primary hemophagocytic lymphohistiocytosis in adults: the utility of family surveys in a single-center study from China. ⁶	Jin Z...Wang Z	29357941	2018
21	Germline cytotoxic lymphocytes defective mutations in Chinese patients with lymphoma. ⁶	Chen X...Liu H	29113160	2017
22	Previously undiagnosed fatal familial haemophagocytic lymphohistiocytosis in a 24-year-old woman. ⁶	Barmettler S...Price C	26903364	2016
23	Targeted high-throughput sequencing for genetic diagnostics of hemophagocytic lymphohistiocytosis. ⁶	Tesi B...Bryceson YT	26684649	2015
24	Accuracy of flow cytometric perforin screening for detecting patients with FHL due to PRF1 mutations. ⁶	Abdalgani M...Marsh RA	26450956	2015
25	Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and clinical findings. ⁶	Willig LK...Kingsmore SF	25937001	2015
26	Patients with Griscelli syndrome and normal pigmentation identify RAB27A mutations that selectively disrupt MUNC13-4 binding. ⁶	Cetica V...Arico M	25312756	2015
27	Mitochondrial dysfunction and risk of cancer. ⁶	Lund M...Vissing J	25742477	2015
28	Primary lymphoma of the brain in a young man whose brother died of hemophagocytic lymphohistiocytosis: case report. ⁶	Dzoljic E...Kostic V	25845254	2015
29	Clinical exome sequencing for genetic identification of rare Mendelian disorders. ⁶	Lee H...Nelson SF	25326637	2014
30	[Analysis of clinical phenotype and genetic mutations of a pedigree of familial hemophagocytic lymphohistiocytosis]. ⁶	Sun S...Gao J	25297583	2014
31	Synergistic defects of different molecules in the cytotoxic pathway lead to clinical familial hemophagocytic lymphohistiocytosis. ⁶	Zhang K...Filipovich AH	24916509	2014
32	Remission and relapse of hemophagocytic lymphohistiocytosis in a patient harboring a PRF1 homozygous mutation: a case report. ⁶	Huang Z...Shen K	23073044	2014
33	Genetic features of late onset primary hemophagocytic lymphohistiocytosis in adolescence or adulthood. ⁶	Wang Y...Ye L	25233452	2014
34	Recurrent subacute post-viral onset of ataxia associated with a PRF1 mutation. ⁶	Dias C...Boerkoel CF	23443029	2013
35	Familial haemophagocytic lymphohistiocytosis in twin infants. ⁶	Higa B...Velankar M	23255033	2013
36	Analyses of the PRF1 gene in individuals with hemophagocytic lymphohystiocytosis reveal the common haplotype R54C/A91V in Colombian unrelated families associated with late onset disease. ⁶	Sanchez IP...Trujillo-Vargas CM	22437823	2012
37	Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. ⁶	Zhizhuo H...Kunling S	21674762	2012
38	Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. ⁶	Zhang K...Filipovich AH	21881043	2011
39	Familial hemophagocytic lymphohistiocytosis in a pediatric patient diagnosed by brain magnetic resonance imaging. ⁶	van Egmond ME...van der Knaap MS	21959744	2011
40	Hydrops fetalis and early neonatal multiple organ failure in familial hemophagocytic lymphohistiocytosis. ⁶	Vermeulen MJ...van de Kamp JM	19595804	2009
41	Temperature sensitivity of human perforin mutants unmasks subtotal loss of cytotoxicity, delayed FHL, and a predisposition to cancer. ⁶	Chia J...Voskoboinik I	19487666	2009
42	Clinical and molecular aspects of Turkish familial hemophagocytic lymphohistiocytosis patients with perforin mutations. ⁶	Okur H...Gurgey A	18190960	2008
43	A teenage boy with late onset hemophagocytic lymphohistiocytosis with predominant neurologic disease and perforin deficiency. ⁶	Beaty AD...Knutsen AP	18074390	2008
44	Patients of African ancestry with hemophagocytic lymphohistiocytosis share a common haplotype of PRF1 with a 50delT mutation. ⁶	Lee SM...Filipovich AH	16860143	2006
45	Aberrant maturation of mutant perforin underlies the clinical diversity of hemophagocytic lymphohistiocytosis. ⁶	Risma KA...Sumegi J	16374518	2006
46	Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. ⁶	Zur Stadt U...Hennies HC	16278825	2006
47	Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations. ⁶	Vogt G...Casanova JL	15924140	2005
48	A proportion of patients with lymphoma may harbor mutations of the perforin gene. ⁶	Clementi R...Roncarolo MG	15728124	2005
49	A functional analysis of the putative polymorphisms A91V and N252S and 22 missense perforin mutations associated with familial hemophagocytic lymphohistiocytosis. ⁶	Voskoboinik I...Trapani JA	15755897	2005
50	Unusual immunophenotype of CD8+ T cells in familial hemophagocytic lymphohistiocytosis. ⁶	Karandikar NJ...McKenna RW	15205266	2004

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Genes for Hemophagocytic Lymphohistiocytosis, Familial, 2

Genes related to Hemophagocytic Lymphohistiocytosis, Familial, 2 (2 elite genes):

(show all 23)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	PRF1	Perforin 1	Protein Coding	1348.14	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative variation ⁷² Genetic Tests ²⁹ Likely pathogenic ⁶ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)	10583959
2	LIFR	LIF Receptor Subunit Alpha	Protein Coding	400	Pathogenic ⁶	14740318
3	CFAP47	Cilia And Flagella Associated Protein 47	Protein Coding	14.46	DISEASES inferred ¹⁵ ¹⁵ ¹⁵
4	SYS1	SYS1 Golgi Trafficking Protein	Protein Coding	7.5	DISEASES inferred ¹⁵
5	ADAMTS20	ADAM Metallopeptidase With Thrombospondin Type 1 Motif 20	Protein Coding	6.68	DISEASES inferred ¹⁵
6	ZNF362	Zinc Finger Protein 362	Protein Coding	6.65	DISEASES inferred ¹⁵
7	UNC119	Unc-119 Lipid Binding Chaperone	Protein Coding	6.52	DISEASES inferred ¹⁵
8	GNLY	Granulysin	Protein Coding	6.36	DISEASES inferred ¹⁵
9	SNORA72	Small Nucleolar RNA, H/ACA Box 72	RNA Gene	6.33	DISEASES inferred ¹⁵
10	CDH15	Cadherin 15	Protein Coding	6.23	DISEASES inferred ¹⁵
11	FHL2	Four And A Half LIM Domains 2	Protein Coding	6.12	DISEASES inferred ¹⁵
12	SNORD75	Small Nucleolar RNA, C/D Box 75	RNA Gene	6.12	DISEASES inferred ¹⁵
13	STX11	Syntaxin 11	Protein Coding	6.08	DISEASES inferred ¹⁵
14	CES1	Carboxylesterase 1	Protein Coding	6.03	DISEASES inferred ¹⁵
15	TCF3	Transcription Factor 3	Protein Coding	5.98	DISEASES inferred ¹⁵
16	GET4	Guided Entry Of Tail-Anchored Proteins Factor 4	Protein Coding	5.95	DISEASES inferred ¹⁵
17	MEX3D	Mex-3 RNA Binding Family Member D	Protein Coding	5.92	DISEASES inferred ¹⁵
18	CDH3	Cadherin 3	Protein Coding	5.87	DISEASES inferred ¹⁵
19	NOTCH1	Notch Receptor 1	Protein Coding	5.78	DISEASES inferred ¹⁵
20	SCRT1	Scratch Family Transcriptional Repressor 1	Protein Coding	5.73	DISEASES inferred ¹⁵
21	NSRP1	Nuclear Speckle Splicing Regulatory Protein 1	Protein Coding	5.69	DISEASES inferred ¹⁵
22	ELMO3	Engulfment And Cell Motility 3	Protein Coding	5.66	DISEASES inferred ¹⁵
23	STXBP2	Syntaxin Binding Protein 2	Protein Coding	5.63	DISEASES inferred ¹⁵

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Variations for Hemophagocytic Lymphohistiocytosis, Familial, 2

ClinVar genetic disease variations for Hemophagocytic Lymphohistiocytosis, Familial, 2:

⁶ (show top 50) (show all 227)

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	Position
1	PRF1	PRF1, 1-BP DEL, 50T	Deletion	Pathogenic	13708		GRCh37: GRCh38:
2	PRF1	NM_001083116.3(PRF1):c.190C>T (p.Gln64Ter)	SNV	Pathogenic	13710	rs104894180	GRCh37: 10:72360469-72360469 GRCh38: 10:70600713-70600713
3	PRF1	NM_001083116.3(PRF1):c.673C>T (p.Arg225Trp)	SNV	Pathogenic	13711	rs28933973	GRCh37: 10:72358804-72358804 GRCh38: 10:70599048-70599048
4	PRF1	NM_001083116.3(PRF1):c.1286G>A (p.Gly429Glu)	SNV	Pathogenic	13712	rs104894181	GRCh37: 10:72358191-72358191 GRCh38: 10:70598435-70598435
5	PRF1	NM_001083116.3(PRF1):c.1034C>T (p.Pro345Leu)	SNV	Pathogenic	13713	rs28933374	GRCh37: 10:72358443-72358443 GRCh38: 10:70598687-70598687
6	PRF1	NM_001083116.3(PRF1):c.836G>A (p.Cys279Tyr)	SNV	Pathogenic	13714	rs104894182	GRCh37: 10:72358641-72358641 GRCh38: 10:70598885-70598885
7	PRF1	NM_001083116.3(PRF1):c.548T>G (p.Val183Gly)	SNV	Pathogenic	13715	rs104894183	GRCh37: 10:72358929-72358929 GRCh38: 10:70599173-70599173
8	PRF1	NM_001083116.3(PRF1):c.1090_1091del (p.Leu364fs)	Deletion	Pathogenic	13721	rs771552960	GRCh37: 10:72358386-72358387 GRCh38: 10:70598630-70598631
9	PRF1	NM_001083116.3(PRF1):c.207del (p.Asp70fs)	Deletion	Pathogenic	13722	rs786205093	GRCh37: 10:72360452-72360452 GRCh38: 10:70600696-70600696
10	PRF1	NM_001083116.3(PRF1):c.1246C>T (p.Gln416Ter)	SNV	Pathogenic	13723	rs193302876	GRCh37: 10:72358231-72358231 GRCh38: 10:70598475-70598475
11	PRF1	NM_001083116.3(PRF1):c.133G>A (p.Gly45Arg)	SNV	Pathogenic	468300	rs578092914	GRCh37: 10:72360526-72360526 GRCh38: 10:70600770-70600770
12	PRF1	NM_001083116.3(PRF1):c.1349C>T (p.Thr450Met)	SNV	Pathogenic	468301	rs189650890	GRCh37: 10:72358128-72358128 GRCh38: 10:70598372-70598372
13	PRF1	NM_001083116.3(PRF1):c.1385C>A (p.Ser462Ter)	SNV	Pathogenic	561093	rs1564723653	GRCh37: 10:72358092-72358092 GRCh38: 10:70598336-70598336
14	PRF1	NC_000010.11:g.(?_70598033)_(70600922_?)del	Deletion	Pathogenic	831689		GRCh37: 10:72357789-72360678 GRCh38:
15	PRF1	NM_001083116.3(PRF1):c.1081A>T (p.Arg361Trp)	SNV	Pathogenic	502548	rs752858869	GRCh37: 10:72358396-72358396 GRCh38: 10:70598640-70598640
16	PRF1	NM_001083116.3(PRF1):c.658G>A (p.Gly220Ser)	SNV	Pathogenic	961631		GRCh37: 10:72358819-72358819 GRCh38: 10:70599063-70599063
17	PRF1	NM_001083116.3(PRF1):c.844AAG[3] (p.Lys285del)	Microsatellite	Pathogenic	971288		GRCh37: 10:72358622-72358624 GRCh38: 10:70598866-70598868
18	PRF1	NM_001083116.3(PRF1):c.781G>A (p.Glu261Lys)	SNV	Pathogenic	976231		GRCh37: 10:72358696-72358696 GRCh38: 10:70598940-70598940
19	PRF1	NM_001083116.3(PRF1):c.50del (p.Leu17fs)	Deletion	Pathogenic	468305	rs147035858	GRCh37: 10:72360609-72360609 GRCh38: 10:70600853-70600853
20	LIFR	NM_001127671.2(LIFR):c.653dup (p.Glu219fs)	Duplication	Pathogenic	281444	rs886042160	GRCh37: 5:38511974-38511975 GRCh38: 5:38511872-38511873
21	PRF1	NM_001083116.3(PRF1):c.666C>A (p.His222Gln)	SNV	Pathogenic	280112	rs751247865	GRCh37: 10:72358811-72358811 GRCh38: 10:70599055-70599055
22	PRF1	NM_001083116.3(PRF1):c.487del (p.His163fs)	Deletion	Pathogenic	848608		GRCh37: 10:72360172-72360172 GRCh38: 10:70600416-70600416
23	PRF1	NM_001083116.3(PRF1):c.1122G>A (p.Trp374Ter)	SNV	Pathogenic	13709	rs104894176	GRCh37: 10:72358355-72358355 GRCh38: 10:70598599-70598599
24	PRF1	NM_001083116.3(PRF1):c.445G>A (p.Gly149Ser)	SNV	Pathogenic	520942	rs147462227	GRCh37: 10:72360214-72360214 GRCh38: 10:70600458-70600458
25	PRF1	NM_001083116.3(PRF1):c.1A>G (p.Met1Val)	SNV	Pathogenic	1029054		GRCh37: 10:72360658-72360658 GRCh38: 10:70600902-70600902
26	PRF1	NM_001083116.3(PRF1):c.148G>A (p.Val50Met)	SNV	Pathogenic/Likely pathogenic	802584	rs776299562	GRCh37: 10:72360511-72360511 GRCh38: 10:70600755-70600755
27	PRF1	NM_001083116.3(PRF1):c.160C>T (p.Arg54Cys)	SNV	Pathogenic/Likely pathogenic	802583	rs200430442	GRCh37: 10:72360499-72360499 GRCh38: 10:70600743-70600743
28	PRF1	NM_001083116.3(PRF1):c.1337A>C (p.Gln446Pro)	SNV	Pathogenic/Likely pathogenic	216986	rs751161742	GRCh37: 10:72358140-72358140 GRCh38: 10:70598384-70598384
29	PRF1	NM_001083116.3(PRF1):c.1120T>G (p.Trp374Gly)	SNV	Likely pathogenic	397653	rs1060499556	GRCh37: 10:72358357-72358357 GRCh38: 10:70598601-70598601
30	PRF1	NM_001083116.3(PRF1):c.1175del (p.Pro392fs)	Deletion	Likely pathogenic	523032	rs1554867753	GRCh37: 10:72358302-72358302 GRCh38: 10:70598546-70598546
31	PRF1	NM_001083116.3(PRF1):c.659G>A (p.Gly220Asp)	SNV	Likely pathogenic	802582	rs202217604	GRCh37: 10:72358818-72358818 GRCh38: 10:70599062-70599062
32	PRF1	NM_001083116.3(PRF1):c.1018G>A (p.Asp340Asn)	SNV	Likely pathogenic	929472	rs754079962	GRCh37: 10:72358459-72358459 GRCh38: 10:70598703-70598703
33	PRF1	NM_001083116.3(PRF1):c.1046T>C (p.Leu349Pro)	SNV	Likely pathogenic	915285		GRCh37: 10:72358431-72358431 GRCh38: 10:70598675-70598675
34	PRF1	NM_001083116.3(PRF1):c.386G>C (p.Trp129Ser)	SNV	Likely pathogenic	548929	rs768849283	GRCh37: 10:72360273-72360273 GRCh38: 10:70600517-70600517
35	PRF1	NM_001083116.3(PRF1):c.1066C>T (p.Arg356Trp)	SNV	Likely pathogenic	959332		GRCh37: 10:72358411-72358411 GRCh38: 10:70598655-70598655
36	PRF1	NM_001083116.3(PRF1):c.921del (p.His308fs)	Deletion	Likely pathogenic	973565		GRCh37: 10:72358556-72358556 GRCh38: 10:70598800-70598800
37	PRF1	NM_001083116.3(PRF1):c.1140G>A (p.Pro380=)	SNV	Conflicting interpretations of pathogenicity	723839	rs144926997	GRCh37: 10:72358337-72358337 GRCh38: 10:70598581-70598581
38	PRF1	NM_001083116.3(PRF1):c.286C>A (p.Arg96=)	SNV	Conflicting interpretations of pathogenicity	300334	rs144024245	GRCh37: 10:72360373-72360373 GRCh38: 10:70600617-70600617
39	PRF1	NM_001083116.3(PRF1):c.111C>T (p.Phe37=)	SNV	Conflicting interpretations of pathogenicity	785783	rs547321451	GRCh37: 10:72360548-72360548 GRCh38: 10:70600792-70600792
40	PRF1	NM_001083116.3(PRF1):c.519G>A (p.Thr173=)	SNV	Conflicting interpretations of pathogenicity	789534	rs112883709	GRCh37: 10:72360140-72360140 GRCh38: 10:70600384-70600384
41	PRF1	NM_001083116.3(PRF1):c.368G>A (p.Arg123His)	SNV	Conflicting interpretations of pathogenicity	789535	rs139336186	GRCh37: 10:72360291-72360291 GRCh38: 10:70600535-70600535
42	PRF1	NM_001083116.3(PRF1):c.630C>T (p.Pro210=)	SNV	Conflicting interpretations of pathogenicity	257405	rs144004164	GRCh37: 10:72358847-72358847 GRCh38: 10:70599091-70599091
43	PRF1	NM_001083116.3(PRF1):c.132C>A (p.Ala44=)	SNV	Conflicting interpretations of pathogenicity	300335	rs181323749	GRCh37: 10:72360527-72360527 GRCh38: 10:70600771-70600771
44	PRF1	NM_001083116.3(PRF1):c.1620A>G (p.Gln540=)	SNV	Conflicting interpretations of pathogenicity	715355	rs149776121	GRCh37: 10:72357857-72357857 GRCh38: 10:70598101-70598101
45	PRF1	NM_001083116.3(PRF1):c.1000G>A (p.Gly334Ser)	SNV	Conflicting interpretations of pathogenicity	536223	rs145463632	GRCh37: 10:72358477-72358477 GRCh38: 10:70598721-70598721
46	PRF1	NM_001083116.3(PRF1):c.807C>T (p.His269=)	SNV	Conflicting interpretations of pathogenicity	257407	rs147453010	GRCh37: 10:72358670-72358670 GRCh38: 10:70598914-70598914
47	PRF1	NM_001083116.3(PRF1):c.519G>C (p.Thr173=)	SNV	Conflicting interpretations of pathogenicity	536227	rs112883709	GRCh37: 10:72360140-72360140 GRCh38: 10:70600384-70600384
48	PRF1	NM_001083116.3(PRF1):c.1153C>T (p.Arg385Trp)	SNV	Conflicting interpretations of pathogenicity	536228	rs551046401	GRCh37: 10:72358324-72358324 GRCh38: 10:70598568-70598568
49	PRF1	NM_001083116.3(PRF1):c.1310C>T (p.Ala437Val)	SNV	Conflicting interpretations of pathogenicity	300327	rs138126912	GRCh37: 10:72358167-72358167 GRCh38: 10:70598411-70598411
50	PRF1	NM_001083116.3(PRF1):c.1444G>T (p.Val482Phe)	SNV	Uncertain significance	578652	rs760962796	GRCh37: 10:72358033-72358033 GRCh38: 10:70598277-70598277

UniProtKB/Swiss-Prot genetic disease variations for Hemophagocytic Lymphohistiocytosis, Familial, 2:

⁷²

#	Symbol	AA change	Variation ID	SNP ID
1	PRF1	p.Val183Gly	VAR_010744	rs104894183
2	PRF1	p.Arg225Trp	VAR_010745	rs28933973
3	PRF1	p.Asn252Ser	VAR_010746	rs28933375
4	PRF1	p.Cys279Tyr	VAR_010747	rs104894182
5	PRF1	p.Pro345Leu	VAR_010748	rs28933374
6	PRF1	p.Gly429Glu	VAR_010749	rs104894181
7	PRF1	p.Val50Met	VAR_010772	rs776299562
8	PRF1	p.Ile224Asn	VAR_010774

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Expression for Hemophagocytic Lymphohistiocytosis, Familial, 2

Search GEO for disease gene expression data for Hemophagocytic Lymphohistiocytosis, Familial, 2.

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Pathways for Hemophagocytic Lymphohistiocytosis, Familial, 2

Pathways related to Hemophagocytic Lymphohistiocytosis, Familial, 2 according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	Presenilin-Mediated Signaling ⁶³	10.95	NOTCH1 CDH3 CDH15

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GO Terms for Hemophagocytic Lymphohistiocytosis, Familial, 2

Cellular components related to Hemophagocytic Lymphohistiocytosis, Familial, 2 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	cytolytic granule	GO:0044194	8.62	PRF1 GNLY

Biological processes related to Hemophagocytic Lymphohistiocytosis, Familial, 2 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	positive regulation of muscle cell differentiation	GO:0051149	8.62	TCF3 CDH15

Molecular functions related to Hemophagocytic Lymphohistiocytosis, Familial, 2 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	bHLH transcription factor binding	GO:0043425	8.62	TCF3 FHL2

Sources

Sources for Hemophagocytic Lymphohistiocytosis, Familial, 2

¹ BioSystems

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¹⁰ dbSNP

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²⁷ GEO DataSets

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³¹ HPO

³² ICD10

³³ ICD10 via Orphanet

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⁵¹ NDF-RT

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⁵⁵ Novus Biologicals

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 05-Apr-2021)

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubMed

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⁶⁵ Reactome

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⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ Tocris

⁷⁰ UMLS

⁷¹ UMLS via Orphanet

⁷² UniProtKB/Swiss-Prot

⁷³ Wikipedia

Hemophagocytic Lymphohistiocytosis, Familial, 2 (FHL2)

Aliases & Classifications for Hemophagocytic Lymphohistiocytosis, Familial, 2

MalaCards integrated aliases for Hemophagocytic Lymphohistiocytosis, Familial, 2:

Characteristics:

OMIM®:

HPO:

Classifications:

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Summaries for Hemophagocytic Lymphohistiocytosis, Familial, 2

Related Diseases for Hemophagocytic Lymphohistiocytosis, Familial, 2

Diseases in the Hemophagocytic Lymphohistiocytosis family:

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Graphical network of the top 20 diseases related to Hemophagocytic Lymphohistiocytosis, Familial, 2:

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Human phenotypes related to Hemophagocytic Lymphohistiocytosis, Familial, 2:

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ClinVar genetic disease variations for Hemophagocytic Lymphohistiocytosis, Familial, 2:

UniProtKB/Swiss-Prot genetic disease variations for Hemophagocytic Lymphohistiocytosis, Familial, 2:

Expression for Hemophagocytic Lymphohistiocytosis, Familial, 2

Pathways for Hemophagocytic Lymphohistiocytosis, Familial, 2

Pathways related to Hemophagocytic Lymphohistiocytosis, Familial, 2 according to GeneCards Suite gene sharing:

GO Terms for Hemophagocytic Lymphohistiocytosis, Familial, 2

Cellular components related to Hemophagocytic Lymphohistiocytosis, Familial, 2 according to GeneCards Suite gene sharing:

Biological processes related to Hemophagocytic Lymphohistiocytosis, Familial, 2 according to GeneCards Suite gene sharing:

Molecular functions related to Hemophagocytic Lymphohistiocytosis, Familial, 2 according to GeneCards Suite gene sharing:

Sources for Hemophagocytic Lymphohistiocytosis, Familial, 2