FHL3
MCID: HMP013
MIFTS: 39

Hemophagocytic Lymphohistiocytosis, Familial, 3 (FHL3)

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

Aliases & Classifications for Hemophagocytic Lymphohistiocytosis, Familial, 3

MalaCards integrated aliases for Hemophagocytic Lymphohistiocytosis, Familial, 3:

Name: Hemophagocytic Lymphohistiocytosis, Familial, 3 57 53 29 13 6 72
Hplh3 57 12 53 74
Hlh3 57 12 53 74
Familial Hemophagocytic Lymphohistiocytosis 3 12 74 15
Fhl3 57 12 74
Lymphohistiocytosis, Hemophagocytic, Familial, Type 3 40

Characteristics:

HPO:

32
hemophagocytic lymphohistiocytosis, familial, 3:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110923
MeSH 44 D051359
MedGen 42 C1837174
UMLS 72 C1837174

Summaries for Hemophagocytic Lymphohistiocytosis, Familial, 3

OMIM : 57 Secretion of the contents of cytolytic granules at the immunologic synapse is a highly regulated process essential for lymphocyte cytotoxicity. This process requires the rapid transfer of perforin (170280)-containing lytic granules to the target cell interface, followed by their docking and fusion with the plasma membrane. Familial hemophagocytic lymphohistiocytosis is a genetically heterogeneous condition characterized by defective cytotoxicity. For a more detailed description of FHL, see 267700. (608898)

MalaCards based summary : Hemophagocytic Lymphohistiocytosis, Familial, 3, also known as hplh3, is related to hemophagocytic lymphohistiocytosis, familial, 2 and hemophagocytic lymphohistiocytosis. An important gene associated with Hemophagocytic Lymphohistiocytosis, Familial, 3 is UNC13D (Unc-13 Homolog D), and among its related pathways/superpathways are Cell Cycle Control of Chromosomal Replication and GADD45 Pathway. Affiliated tissues include brain, and related phenotypes are anemia and granulocytopenia

Disease Ontology : 12 A hemophagocytic lymphohistiocytosis that has material basis in a mutation of UNC13D on chromosome 17q25.1.

UniProtKB/Swiss-Prot : 74 Familial hemophagocytic lymphohistiocytosis 3: 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, 3

Graphical network of the top 20 diseases related to Hemophagocytic Lymphohistiocytosis, Familial, 3:



Diseases related to Hemophagocytic Lymphohistiocytosis, Familial, 3

Symptoms & Phenotypes for Hemophagocytic Lymphohistiocytosis, Familial, 3

Human phenotypes related to Hemophagocytic Lymphohistiocytosis, Familial, 3:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 anemia 32 very rare (1%) HP:0001903
2 granulocytopenia 32 very rare (1%) HP:0001913
3 reduced natural killer cell activity 32 very rare (1%) HP:0012178
4 fever 32 HP:0001945
5 hypertriglyceridemia 32 HP:0002155
6 hepatosplenomegaly 32 HP:0001433
7 hypofibrinogenemia 32 HP:0011900
8 hemophagocytosis 32 HP:0012156

Clinical features from OMIM:

608898

Drugs & Therapeutics for Hemophagocytic Lymphohistiocytosis, Familial, 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Maximizing Mechanisms of Muscle Hypertrophy to Combat Sarcopenia in Older Adults Completed NCT02442479

Search NIH Clinical Center for Hemophagocytic Lymphohistiocytosis, Familial, 3

Genetic Tests for Hemophagocytic Lymphohistiocytosis, Familial, 3

Genetic tests related to Hemophagocytic Lymphohistiocytosis, Familial, 3:

# Genetic test Affiliating Genes
1 Hemophagocytic Lymphohistiocytosis, Familial, 3 29 UNC13D

Anatomical Context for Hemophagocytic Lymphohistiocytosis, Familial, 3

MalaCards organs/tissues related to Hemophagocytic Lymphohistiocytosis, Familial, 3:

41
Brain

Publications for Hemophagocytic Lymphohistiocytosis, Familial, 3

Articles related to Hemophagocytic Lymphohistiocytosis, Familial, 3:

# Title Authors PMID Year
1
Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. 8 71
16825436 2006
2
Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. 8 71
16278825 2006
3
Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). 8 71
14622600 2003
4
Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis. 8
17993578 2008
5
Hemophagocytic Lymphohistiocytosis, Familial 71
20301617 2006
6
Pho4 Is Essential for Dissemination of Cryptococcus neoformans to the Host Brain by Promoting Phosphate Uptake and Growth at Alkaline pH. 38
28144629 2017

Variations for Hemophagocytic Lymphohistiocytosis, Familial, 3

ClinVar genetic disease variations for Hemophagocytic Lymphohistiocytosis, Familial, 3:

6 (show top 50) (show all 134)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 UNC13D NM_199242.2(UNC13D): c.2695C> T (p.Arg899Ter) single nucleotide variant Pathogenic rs766657895 17:73826673-73826673 17:75830592-75830592
2 UNC13D NM_199242.2(UNC13D): c.2346_2349del (p.Arg782fs) deletion Pathogenic rs764196809 17:73830174-73830177 17:75834093-75834096
3 UNC13D NM_199242.2(UNC13D): c.118-308C> T single nucleotide variant Pathogenic rs959968589 17:73839908-73839908 17:75843827-75843827
4 UNC13D NM_199242.2(UNC13D): c.1828_1839del (p.Arg610_Gln613del) deletion Pathogenic rs796065024 17:73831499-73831510 17:75835418-75835429
5 UNC13D NM_199242.2(UNC13D): c.216del (p.Asn73fs) deletion Pathogenic rs796065025 17:73839285-73839285 17:75843204-75843204
6 UNC13D NM_199242.2(UNC13D): c.1754dup (p.His586fs) duplication Pathogenic rs796065026 17:73831584-73831584 17:75835503-75835503
7 UNC13D NM_199242.2(UNC13D): c.1389+1G> A single nucleotide variant Pathogenic rs777759523 17:73832419-73832419 17:75836338-75836338
8 UNC13D NM_199242.2(UNC13D): c.766C> T (p.Arg256Ter) single nucleotide variant Pathogenic rs121434352 17:73836398-73836398 17:75840317-75840317
9 UNC13D NM_199242.2(UNC13D): c.753+1G> T single nucleotide variant Pathogenic rs201908137 17:73836587-73836587 17:75840506-75840506
10 UNC13D NM_199242.2(UNC13D): c.1208T> C (p.Leu403Pro) single nucleotide variant Pathogenic rs121434353 17:73832743-73832743 17:75836662-75836662
11 UNC13D NM_199242.2(UNC13D): c.2570T> G (p.Phe857Cys) single nucleotide variant Pathogenic rs121434354 17:73827234-73827234 17:75831153-75831153
12 UNC13D NM_199242.2(UNC13D): c.1472T> A (p.Leu491Ter) single nucleotide variant Pathogenic rs1555601754 17:73832165-73832165 17:75836084-75836084
13 UNC13D NM_199242.2(UNC13D): c.3011_3014dup (p.Tyr1006fs) duplication Pathogenic 17:73825005-73825008 17:75828924-75828927
14 UNC13D NM_199242.2(UNC13D): c.1768C> T (p.Gln590Ter) single nucleotide variant Pathogenic 17:73831570-73831570 17:75835489-75835489
15 UNC13D NM_199242.2(UNC13D): c.2258_2267delinsTACCTTGTCCGA (p.Gly753fs) indel Pathogenic 17:73830437-73830446 17:75834356-75834365
16 UNC13D NM_199242.2(UNC13D): c.520C> T (p.Gln174Ter) single nucleotide variant Pathogenic 17:73838563-73838563 17:75842482-75842482
17 UNC13D NM_199242.2(UNC13D): c.2293G> T (p.Glu765Ter) single nucleotide variant Pathogenic 17:73830411-73830411 17:75834330-75834330
18 UNC13D NM_199242.2(UNC13D): c.2447+1G> A single nucleotide variant Likely pathogenic 17:73829046-73829046 17:75832965-75832965
19 UNC13D NM_199242.2(UNC13D): c.859-1G> C single nucleotide variant Likely pathogenic 17:73836192-73836192 17:75840111-75840111
20 UNC13D NM_199242.2(UNC13D): c.569+5G> A single nucleotide variant Likely pathogenic 17:73838509-73838509 17:75842428-75842428
21 UNC13D NM_199242.2(UNC13D): c.247C> T (p.Arg83Ter) single nucleotide variant Likely pathogenic 17:73839254-73839254 17:75843173-75843173
22 UNC13D NM_199242.2(UNC13D): c.1727+1G> A single nucleotide variant Likely pathogenic rs754882266 17:73831727-73831727 17:75835646-75835646
23 UNC13D NM_199242.2(UNC13D): c.1299-1G> A single nucleotide variant Likely pathogenic rs1555601863 17:73832511-73832511 17:75836430-75836430
24 UNC13D NM_199242.2(UNC13D): c.2709+1G> A single nucleotide variant Likely pathogenic rs1555600214 17:73826658-73826658 17:75830577-75830577
25 UNC13D NM_199242.2(UNC13D): c.2542A> C (p.Ile848Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs144968313 17:73827335-73827335 17:75831254-75831254
26 UNC13D NM_199242.2(UNC13D): c.444G> A (p.Gly148=) single nucleotide variant Conflicting interpretations of pathogenicity rs373551579 17:73838639-73838639 17:75842558-75842558
27 UNC13D NM_199242.2(UNC13D): c.2341G> A (p.Val781Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs149871493 17:73830182-73830182 17:75834101-75834101
28 UNC13D NM_199242.2(UNC13D): c.227C> T (p.Thr76Met) single nucleotide variant Conflicting interpretations of pathogenicity rs78028658 17:73839274-73839274 17:75843193-75843193
29 UNC13D NM_199242.2(UNC13D): c.2983G> C (p.Ala995Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs138760432 17:73825036-73825036 17:75828955-75828955
30 UNC13D NM_199242.2(UNC13D): c.2335G> A (p.Val779Met) single nucleotide variant Conflicting interpretations of pathogenicity rs113861754 17:73830188-73830188 17:75834107-75834107
31 UNC13D NM_199242.2(UNC13D): c.1228A> C (p.Ile410Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs117221419 17:73832723-73832723 17:75836642-75836642
32 UNC13D NM_199242.2(UNC13D): c.2052C> G (p.Leu684=) single nucleotide variant Conflicting interpretations of pathogenicity rs150861045 17:73830738-73830738 17:75834657-75834657
33 UNC13D NM_199242.2(UNC13D): c.2896C> T (p.Arg966Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs118049905 17:73826167-73826167 17:75830086-75830086
34 UNC13D NM_199242.2(UNC13D): c.99G> A (p.Pro33=) single nucleotide variant Conflicting interpretations of pathogenicity rs147886860 17:73840320-73840320 17:75844239-75844239
35 UNC13D NM_199242.2(UNC13D): c.24G> A (p.Pro8=) single nucleotide variant Conflicting interpretations of pathogenicity rs143320460 17:73840395-73840395 17:75844314-75844314
36 UNC13D NM_199242.2(UNC13D): c.904C> T (p.Leu302Phe) single nucleotide variant Conflicting interpretations of pathogenicity rs55661958 17:73836146-73836146 17:75840065-75840065
37 UNC13D NM_199242.2(UNC13D): c.3033C> T (p.Ala1011=) single nucleotide variant Conflicting interpretations of pathogenicity rs144730861 17:73824986-73824986 17:75828905-75828905
38 UNC13D NM_199242.2(UNC13D): c.2044C> T (p.Arg682Cys) single nucleotide variant Uncertain significance rs755931780 17:73830746-73830746 17:75834665-75834665
39 UNC13D NM_199242.2(UNC13D): c.1772C> T (p.Pro591Leu) single nucleotide variant Uncertain significance rs144852879 17:73831566-73831566 17:75835485-75835485
40 UNC13D NM_199242.2(UNC13D): c.3079G> A (p.Gly1027Arg) single nucleotide variant Uncertain significance rs776703437 17:73824940-73824940 17:75828859-75828859
41 UNC13D NM_199242.2(UNC13D): c.3141C> A (p.Pro1047=) single nucleotide variant Uncertain significance rs866899109 17:73824878-73824878 17:75828797-75828797
42 UNC13D NM_199242.2(UNC13D): c.972C> T (p.Asp324=) single nucleotide variant Uncertain significance rs368990813 17:73836003-73836003 17:75839922-75839922
43 UNC13D NM_199242.2(UNC13D): c.2761C> T (p.Arg921Cys) single nucleotide variant Uncertain significance rs373079371 17:73826512-73826512 17:75830431-75830431
44 UNC13D NM_199242.2(UNC13D): c.1580G> A (p.Arg527Gln) single nucleotide variant Uncertain significance rs775555882 17:73831952-73831952 17:75835871-75835871
45 UNC13D NM_199242.2(UNC13D): c.1240C> T (p.Arg414Cys) single nucleotide variant Uncertain significance rs750811263 17:73832711-73832711 17:75836630-75836630
46 UNC13D NM_199242.2(UNC13D): c.2588G> A (p.Gly863Asp) single nucleotide variant Uncertain significance rs140184929 17:73827216-73827216 17:75831135-75831135
47 UNC13D NM_199242.2(UNC13D): c.1607G> T (p.Arg536Leu) single nucleotide variant Uncertain significance rs143305366 17:73831848-73831848 17:75835767-75835767
48 UNC13D NM_199242.2(UNC13D): c.859-4G> A single nucleotide variant Uncertain significance rs373239557 17:73836195-73836195 17:75840114-75840114
49 UNC13D NM_199242.2(UNC13D): c.3160A> G (p.Ile1054Val) single nucleotide variant Uncertain significance rs150952348 17:73824159-73824159 17:75828078-75828078
50 UNC13D NM_199242.2(UNC13D): c.70C> A (p.Arg24Ser) single nucleotide variant Uncertain significance rs749234163 17:73840349-73840349 17:75844268-75844268

Expression for Hemophagocytic Lymphohistiocytosis, Familial, 3

Search GEO for disease gene expression data for Hemophagocytic Lymphohistiocytosis, Familial, 3.

Pathways for Hemophagocytic Lymphohistiocytosis, Familial, 3

Pathways related to Hemophagocytic Lymphohistiocytosis, Familial, 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.89 CDK8 CDK7
2 10.66 CDK8 CDK7
3 10.43 S100A10 ANXA2
4 9.74 S100A10 ANXA2

GO Terms for Hemophagocytic Lymphohistiocytosis, Familial, 3

Cellular components related to Hemophagocytic Lymphohistiocytosis, Familial, 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 collagen-containing extracellular matrix GO:0062023 9.33 VWF S100A10 ANXA2
2 extrinsic component of plasma membrane GO:0019897 8.96 S100A10 ANXA2
3 Weibel-Palade body GO:0033093 8.62 VWF UNC13D

Biological processes related to Hemophagocytic Lymphohistiocytosis, Familial, 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein heterotetramerization GO:0051290 9.32 S100A10 ANXA2
2 positive regulation of substrate adhesion-dependent cell spreading GO:1900026 9.26 UNC13D S100A10
3 vesicle budding from membrane GO:0006900 9.16 S100A10 ANXA2
4 positive regulation of binding GO:0051099 8.96 S100A10 ANXA2
5 membrane raft assembly GO:0001765 8.62 S100A10 ANXA2

Molecular functions related to Hemophagocytic Lymphohistiocytosis, Familial, 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.9 VWF UNC13D SNAI1 S100A10 RTL10 GET4
2 E-box binding GO:0070888 9.26 SNAI1 ASCL1
3 cyclin-dependent protein serine/threonine kinase activity GO:0004693 8.96 CDK8 CDK7
4 RNA polymerase II CTD heptapeptide repeat kinase activity GO:0008353 8.62 CDK8 CDK7

Sources for Hemophagocytic Lymphohistiocytosis, Familial, 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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36 IUPHAR
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44 MeSH
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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