FHL2
MCID: HMP012
MIFTS: 45

Hemophagocytic Lymphohistiocytosis, Familial, 2 (FHL2) malady

Categories: Genetic diseases, Rare diseases, Immune diseases, Blood diseases, Neuronal diseases

Aliases & Classifications for Hemophagocytic Lymphohistiocytosis, Familial, 2

Aliases & Descriptions for Hemophagocytic Lymphohistiocytosis, Familial, 2:

Name: Hemophagocytic Lymphohistiocytosis, Familial, 2 54 50 13 69
Familial Hemophagocytic Lymphohistiocytosis 2 12 24 66 29 14
Fhl2 12 50 24 66
Hplh2 12 50 66
Hlh2 12 50 66

Characteristics:

HPO:

32
hemophagocytic lymphohistiocytosis, familial, 2:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 54 603553
Disease Ontology 12 DOID:0110922
MedGen 40 C1863727
MeSH 42 D051359

Summaries for Hemophagocytic Lymphohistiocytosis, Familial, 2

OMIM : 54 Familial hemophagocytic lymphohistiocytosis-2 (FHL2) is an autosomal recessive disorder of immune dysregulation with... (603553) more...

MalaCards based summary : Hemophagocytic Lymphohistiocytosis, Familial, 2, also known as familial hemophagocytic lymphohistiocytosis 2, is related to hemophagocytic lymphohistiocytosis and rhabdomyosarcoma, and has symptoms including ataxia, seizures and hemiplegia. An important gene associated with Hemophagocytic Lymphohistiocytosis, Familial, 2 is PRF1 (Perforin 1), and among its related pathways/superpathways are Signaling by PTK6 and Bacterial invasion of epithelial cells. The drugs alemtuzumab and Cyclophosphamide have been mentioned in the context of this disorder. Affiliated tissues include t cells, bone and liver, and related phenotypes are cardiovascular system and respiratory system

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

UniProtKB/Swiss-Prot : 66 Familial hemophagocytic lymphohistiocytosis 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.

Related Diseases for Hemophagocytic Lymphohistiocytosis, Familial, 2

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



Diseases related to Hemophagocytic Lymphohistiocytosis, Familial, 2

Symptoms & Phenotypes for Hemophagocytic Lymphohistiocytosis, Familial, 2

Symptoms by clinical synopsis from OMIM:

603553

Clinical features from OMIM:

603553

Human phenotypes related to Hemophagocytic Lymphohistiocytosis, Familial, 2:

32 (show all 32)
id Description HPO Frequency HPO Source Accession
1 ataxia 32 HP:0001251
2 seizures 32 HP:0001250
3 hemiplegia 32 HP:0002301
4 muscular hypotonia 32 HP:0001252
5 failure to thrive 32 HP:0001508
6 encephalitis 32 HP:0002383
7 tetraplegia 32 HP:0002445
8 global developmental delay 32 HP:0001263
9 splenomegaly 32 HP:0001744
10 hepatomegaly 32 HP:0002240
11 increased intracranial pressure 32 HP:0002516
12 hypertonia 32 HP:0001276
13 hypertriglyceridemia 32 HP:0002155
14 anemia 32 HP:0001903
15 irritability 32 HP:0000737
16 thrombocytopenia 32 HP:0001873
17 jaundice 32 HP:0000952
18 coma 32 HP:0001259
19 hyponatremia 32 HP:0002902
20 meningitis 32 HP:0001287
21 lymphadenopathy 32 HP:0002716
22 increased serum ferritin 32 HP:0003281
23 leukopenia 32 HP:0001882
24 prolonged prothrombin time 32 HP:0008151
25 increased csf protein 32 HP:0002922
26 hypoalbuminemia 32 HP:0003073
27 hypoproteinemia 32 HP:0003075
28 increased total bilirubin 32 HP:0003573
29 generalized edema 32 HP:0007430
30 hemophagocytosis 32 HP:0012156
31 hypofibrinogenemia 32 HP:0011900
32 csf pleocytosis 32 HP:0012229

UMLS symptoms related to Hemophagocytic Lymphohistiocytosis, Familial, 2:


ataxia, hemiplegia, icterus, seizures, bulging fontanelle

MGI Mouse Phenotypes related to Hemophagocytic Lymphohistiocytosis, Familial, 2:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.35 DOCK1 HPSE IFT122 PRF1 WDR35
2 respiratory system MP:0005388 8.92 FOXD1 HPSE WDR35 DOCK1

Drugs & Therapeutics for Hemophagocytic Lymphohistiocytosis, Familial, 2

Drugs for Hemophagocytic Lymphohistiocytosis, Familial, 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 38)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
alemtuzumab Approved, Investigational Phase 2,Phase 1 216503-57-0
2
Cyclophosphamide Approved, Investigational Phase 2,Phase 1 50-18-0, 6055-19-2 2907
3
Cytarabine Approved, Investigational Phase 2 147-94-4 6253
4
Busulfan Approved, Investigational Phase 1, Phase 2 55-98-1 2478
5
Fludarabine Approved Phase 1, Phase 2 21679-14-1, 75607-67-9 30751
6
Melphalan Approved Phase 1, Phase 2 148-82-3 4053 460612
7
Methylprednisolone Approved, Vet_approved Phase 1, Phase 2 83-43-2 6741
8
Prednisolone Approved, Vet_approved Phase 1, Phase 2 50-24-8 5755
9
Tacrolimus Approved, Investigational Phase 1, Phase 2 104987-11-3 445643 439492
10
Thiotepa Approved Phase 1, Phase 2 52-24-4 5453
11 Alkylating Agents Phase 2,Phase 1
12 Anti-Infective Agents Phase 2
13 Antimetabolites Phase 2,Phase 1
14 Antimetabolites, Antineoplastic Phase 2,Phase 1
15 Antineoplastic Agents, Alkylating Phase 2,Phase 1
16 Antirheumatic Agents Phase 2,Phase 1
17 Antiviral Agents Phase 2
18 Immunosuppressive Agents Phase 2,Phase 1
19 Antiemetics Phase 1, Phase 2
20 Anti-Inflammatory Agents Phase 1, Phase 2
21 Antineoplastic Agents, Hormonal Phase 1, Phase 2
22 Autonomic Agents Phase 1, Phase 2
23 Calcineurin Inhibitors Phase 1, Phase 2
24 Gastrointestinal Agents Phase 1, Phase 2
25 glucocorticoids Phase 1, Phase 2
26 Hormone Antagonists Phase 1, Phase 2
27 Hormones Phase 1, Phase 2
28 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 1, Phase 2
29 Liver Extracts Phase 1, Phase 2
30 Methylprednisolone acetate Phase 1, Phase 2
31 Methylprednisolone Hemisuccinate Phase 1, Phase 2
32 Neuroprotective Agents Phase 1, Phase 2
33 Peripheral Nervous System Agents Phase 1, Phase 2
34 Pharmaceutical Solutions Phase 1, Phase 2
35 Prednisolone acetate Phase 1, Phase 2
36 Prednisolone hemisuccinate Phase 1, Phase 2
37 Prednisolone phosphate Phase 1, Phase 2
38 Protective Agents Phase 1, Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase
1 T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts Recruiting NCT00368355 Phase 2
2 CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant Recruiting NCT02061800 Phase 1, Phase 2
3 Administration of Donor T Cells With the Caspase-9 Suicide Gene Active, not recruiting NCT01494103 Phase 1
4 CASPALLO: Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene Active, not recruiting NCT00710892 Phase 1

Search NIH Clinical Center for Hemophagocytic Lymphohistiocytosis, Familial, 2

Genetic Tests for Hemophagocytic Lymphohistiocytosis, Familial, 2

Genetic tests related to Hemophagocytic Lymphohistiocytosis, Familial, 2:

id Genetic test Affiliating Genes
1 Hemophagocytic Lymphohistiocytosis, Familial, 2 29
2 Familial Hemophagocytic Lymphohistiocytosis 2 24 PRF1

Anatomical Context for Hemophagocytic Lymphohistiocytosis, Familial, 2

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

39
T Cells, Bone, Liver, Bone Marrow, Lymph Node, Spleen, Nk Cells

Publications for Hemophagocytic Lymphohistiocytosis, Familial, 2

Variations for Hemophagocytic Lymphohistiocytosis, Familial, 2

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

66
id 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
8 PRF1 p.Ile224Asn VAR_010774

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

6 (show all 14)
id Gene Variation Type Significance SNP ID Assembly Location
1 PRF1 PRF1, 1-BP DEL, 50T deletion Pathogenic
2 PRF1 NM_001083116.1(PRF1): c.1122G> A (p.Trp374Ter) single nucleotide variant Pathogenic rs104894176 GRCh37 Chromosome 10, 72358355: 72358355
3 PRF1 NM_001083116.1(PRF1): c.190C> T (p.Gln64Ter) single nucleotide variant Pathogenic rs104894180 GRCh37 Chromosome 10, 72360469: 72360469
4 PRF1 NM_001083116.1(PRF1): c.673C> T (p.Arg225Trp) single nucleotide variant Pathogenic rs28933973 GRCh37 Chromosome 10, 72358804: 72358804
5 PRF1 NM_001083116.1(PRF1): c.1286G> A (p.Gly429Glu) single nucleotide variant Pathogenic rs104894181 GRCh37 Chromosome 10, 72358191: 72358191
6 PRF1 NM_001083116.1(PRF1): c.1034C> T (p.Pro345Leu) single nucleotide variant Pathogenic rs28933374 GRCh37 Chromosome 10, 72358443: 72358443
7 PRF1 NM_001083116.1(PRF1): c.836G> A (p.Cys279Tyr) single nucleotide variant Pathogenic rs104894182 GRCh37 Chromosome 10, 72358641: 72358641
8 PRF1 NM_001083116.1(PRF1): c.548T> G (p.Val183Gly) single nucleotide variant Pathogenic rs104894183 GRCh37 Chromosome 10, 72358929: 72358929
9 PRF1 NM_001083116.1(PRF1): c.1304C> T (p.Thr435Met) single nucleotide variant Pathogenic rs28933376 GRCh37 Chromosome 10, 72358173: 72358173
10 PRF1 NM_005041.4(PRF1): c.1090_1091delCT (p.Leu364Glufs) deletion Pathogenic rs771552960 GRCh38 Chromosome 10, 70598630: 70598631
11 PRF1 NM_005041.4(PRF1): c.207delC (p.Asp70Thrfs) deletion Pathogenic rs786205093 GRCh37 Chromosome 10, 72360452: 72360452
12 PRF1 NM_001083116.1(PRF1): c.1246C> T (p.Gln416Ter) single nucleotide variant Pathogenic rs193302876 GRCh37 Chromosome 10, 72358231: 72358231
13 PRF1 NM_005041.4(PRF1): c.1337A> C (p.Gln446Pro) single nucleotide variant Likely pathogenic rs751161742 GRCh38 Chromosome 10, 70598384: 70598384
14 PRF1 NM_001083116.1(PRF1): c.1120T> G (p.Trp374Gly) single nucleotide variant Likely pathogenic rs1060499556 GRCh37 Chromosome 10, 72358357: 72358357

Expression for Hemophagocytic Lymphohistiocytosis, Familial, 2

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

Pathways for Hemophagocytic Lymphohistiocytosis, Familial, 2

GO Terms for Hemophagocytic Lymphohistiocytosis, Familial, 2

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

id Name GO ID Score Top Affiliating Genes
1 ciliary basal body GO:0036064 9.16 IFT122 WDR35
2 ciliary tip GO:0097542 8.96 IFT122 WDR35
3 intraciliary transport particle A GO:0030991 8.62 IFT122 WDR35

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

id Name GO ID Score Top Affiliating Genes
1 Fc-gamma receptor signaling pathway involved in phagocytosis GO:0038096 9.37 DOCK1 ELMO2
2 vascular endothelial growth factor receptor signaling pathway GO:0048010 9.32 DOCK1 ELMO2
3 phagocytosis GO:0006909 9.26 DOCK1 ELMO2
4 intraciliary transport involved in cilium assembly GO:0035735 9.16 IFT122 WDR35
5 protein localization to cilium GO:0061512 8.96 IFT122 WDR35
6 intraciliary retrograde transport GO:0035721 8.62 IFT122 WDR35

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

id Name GO ID Score Top Affiliating Genes
1 SH3 domain binding GO:0017124 8.62 DOCK1 ELMO2

Sources for Hemophagocytic Lymphohistiocytosis, Familial, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
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48 NDF-RT
51 NINDS
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60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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