MCID: HMP013
MIFTS: 32

Hemophagocytic Lymphohistiocytosis, Familial, 3

Categories: Genetic diseases, Rare diseases, Immune diseases, Blood diseases, Neuronal 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 73
Hplh3 57 12 53 75
Hlh3 57 12 53 75
Familial Hemophagocytic Lymphohistiocytosis 3 12 75 15
Fhl3 57 12 75
Lymphohistiocytosis, Hemophagocytic, Familial, Type 3 40

Characteristics:

HPO:

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


Classifications:



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 and glioma. 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. Related phenotypes are hepatosplenomegaly and anemia

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

UniProtKB/Swiss-Prot : 75 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

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

Diseases related to Hemophagocytic Lymphohistiocytosis, Familial, 3 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hemophagocytic lymphohistiocytosis 10.1
2 glioma 10.1
3 breast cancer 9.9
4 deep angioma 9.8 ANXA2 VWF
5 intramuscular hemangioma 9.6 ANXA2 VWF

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

Clinical features from OMIM:

608898

Human phenotypes related to Hemophagocytic Lymphohistiocytosis, Familial, 3:

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

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 Not Applicable

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

Publications for Hemophagocytic Lymphohistiocytosis, Familial, 3

Articles related to Hemophagocytic Lymphohistiocytosis, Familial, 3:

# Title Authors Year
1
The 253-kb inversion and deep intronic mutations in UNC13D are present in North American patients with familial hemophagocytic lymphohistiocytosis 3. ( 24470399 )
2014

Variations for Hemophagocytic Lymphohistiocytosis, Familial, 3

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

6
(show top 50) (show all 136)
# Gene Variation Type Significance SNP ID Assembly Location
1 UNC13D NM_199242.2(UNC13D): c.1828_1839delCGCGCTGTGCAG (p.Arg610_Gln613del) deletion Pathogenic rs796065024 GRCh38 Chromosome 17, 75835418: 75835429
2 UNC13D NM_199242.2(UNC13D): c.1828_1839delCGCGCTGTGCAG (p.Arg610_Gln613del) deletion Pathogenic rs796065024 GRCh37 Chromosome 17, 73831499: 73831510
3 UNC13D NM_199242.2(UNC13D): c.216delC (p.Asn73Thrfs) deletion Pathogenic rs796065025 GRCh38 Chromosome 17, 75843204: 75843204
4 UNC13D NM_199242.2(UNC13D): c.216delC (p.Asn73Thrfs) deletion Pathogenic rs796065025 GRCh37 Chromosome 17, 73839285: 73839285
5 UNC13D NM_199242.2(UNC13D): c.1754dupT (p.His586Profs) duplication Pathogenic rs796065026 GRCh37 Chromosome 17, 73831584: 73831584
6 UNC13D NM_199242.2(UNC13D): c.1754dupT (p.His586Profs) duplication Pathogenic rs796065026 GRCh38 Chromosome 17, 75835503: 75835503
7 UNC13D NM_199242.2(UNC13D): c.1389+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs777759523 GRCh37 Chromosome 17, 73832419: 73832419
8 UNC13D NM_199242.2(UNC13D): c.1389+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs777759523 GRCh38 Chromosome 17, 75836338: 75836338
9 UNC13D NM_199242.2(UNC13D): c.766C> T (p.Arg256Ter) single nucleotide variant Pathogenic rs121434352 GRCh37 Chromosome 17, 73836398: 73836398
10 UNC13D NM_199242.2(UNC13D): c.766C> T (p.Arg256Ter) single nucleotide variant Pathogenic rs121434352 GRCh38 Chromosome 17, 75840317: 75840317
11 UNC13D NM_199242.2(UNC13D): c.753+1G> T single nucleotide variant Pathogenic rs201908137 GRCh38 Chromosome 17, 75840506: 75840506
12 UNC13D NM_199242.2(UNC13D): c.753+1G> T single nucleotide variant Pathogenic rs201908137 GRCh37 Chromosome 17, 73836587: 73836587
13 UNC13D NM_199242.2(UNC13D): c.1208T> C (p.Leu403Pro) single nucleotide variant Pathogenic rs121434353 GRCh37 Chromosome 17, 73832743: 73832743
14 UNC13D NM_199242.2(UNC13D): c.1208T> C (p.Leu403Pro) single nucleotide variant Pathogenic rs121434353 GRCh38 Chromosome 17, 75836662: 75836662
15 UNC13D NM_199242.2(UNC13D): c.2570T> G (p.Phe857Cys) single nucleotide variant Pathogenic rs121434354 GRCh37 Chromosome 17, 73827234: 73827234
16 UNC13D NM_199242.2(UNC13D): c.2570T> G (p.Phe857Cys) single nucleotide variant Pathogenic rs121434354 GRCh38 Chromosome 17, 75831153: 75831153
17 UNC13D NM_199242.2(UNC13D): c.2588G> A (p.Gly863Asp) single nucleotide variant Uncertain significance rs140184929 GRCh37 Chromosome 17, 73827216: 73827216
18 UNC13D NM_199242.2(UNC13D): c.2588G> A (p.Gly863Asp) single nucleotide variant Uncertain significance rs140184929 GRCh38 Chromosome 17, 75831135: 75831135
19 UNC13D NM_199242.2(UNC13D): c.1228A> C (p.Ile410Leu) single nucleotide variant Uncertain significance rs117221419 GRCh38 Chromosome 17, 75836642: 75836642
20 UNC13D NM_199242.2(UNC13D): c.1228A> C (p.Ile410Leu) single nucleotide variant Uncertain significance rs117221419 GRCh37 Chromosome 17, 73832723: 73832723
21 UNC13D NM_199242.2(UNC13D): c.1579C> T (p.Arg527Trp) single nucleotide variant Benign/Likely benign rs75366116 GRCh37 Chromosome 17, 73831953: 73831953
22 UNC13D NM_199242.2(UNC13D): c.1579C> T (p.Arg527Trp) single nucleotide variant Benign/Likely benign rs75366116 GRCh38 Chromosome 17, 75835872: 75835872
23 UNC13D NM_199242.2(UNC13D): c.3252T> C (p.His1084=) single nucleotide variant Benign/Likely benign rs61753922 GRCh38 Chromosome 17, 75827986: 75827986
24 UNC13D NM_199242.2(UNC13D): c.3252T> C (p.His1084=) single nucleotide variant Benign/Likely benign rs61753922 GRCh37 Chromosome 17, 73824067: 73824067
25 UNC13D NM_199242.2(UNC13D): c.3198A> G (p.Glu1066=) single nucleotide variant Benign rs7210574 GRCh38 Chromosome 17, 75828040: 75828040
26 UNC13D NM_199242.2(UNC13D): c.3198A> G (p.Glu1066=) single nucleotide variant Benign rs7210574 GRCh37 Chromosome 17, 73824121: 73824121
27 UNC13D NM_199242.2(UNC13D): c.2896C> T (p.Arg966Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs118049905 GRCh37 Chromosome 17, 73826167: 73826167
28 UNC13D NM_199242.2(UNC13D): c.2896C> T (p.Arg966Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs118049905 GRCh38 Chromosome 17, 75830086: 75830086
29 UNC13D NM_199242.2(UNC13D): c.2782C> T (p.Arg928Cys) single nucleotide variant Benign/Likely benign rs35037984 GRCh38 Chromosome 17, 75830410: 75830410
30 UNC13D NM_199242.2(UNC13D): c.2782C> T (p.Arg928Cys) single nucleotide variant Benign/Likely benign rs35037984 GRCh37 Chromosome 17, 73826491: 73826491
31 UNC13D NM_199242.2(UNC13D): c.2599A> G (p.Lys867Glu) single nucleotide variant Benign rs1135688 GRCh38 Chromosome 17, 75831124: 75831124
32 UNC13D NM_199242.2(UNC13D): c.2599A> G (p.Lys867Glu) single nucleotide variant Benign rs1135688 GRCh37 Chromosome 17, 73827205: 73827205
33 UNC13D NM_199242.2(UNC13D): c.2052C> G (p.Leu684=) single nucleotide variant Conflicting interpretations of pathogenicity rs150861045 GRCh38 Chromosome 17, 75834657: 75834657
34 UNC13D NM_199242.2(UNC13D): c.2052C> G (p.Leu684=) single nucleotide variant Conflicting interpretations of pathogenicity rs150861045 GRCh37 Chromosome 17, 73830738: 73830738
35 UNC13D NM_199242.2(UNC13D): c.1977C> T (p.Thr659=) single nucleotide variant Benign/Likely benign rs2290770 GRCh37 Chromosome 17, 73831016: 73831016
36 UNC13D NM_199242.2(UNC13D): c.1977C> T (p.Thr659=) single nucleotide variant Benign/Likely benign rs2290770 GRCh38 Chromosome 17, 75834935: 75834935
37 UNC13D NM_199242.2(UNC13D): c.888G> C (p.Pro296=) single nucleotide variant Benign rs7223416 GRCh38 Chromosome 17, 75840081: 75840081
38 UNC13D NM_199242.2(UNC13D): c.888G> C (p.Pro296=) single nucleotide variant Benign rs7223416 GRCh37 Chromosome 17, 73836162: 73836162
39 UNC13D NM_199242.2(UNC13D): c.847A> G (p.Ile283Val) single nucleotide variant Benign rs61754871 GRCh38 Chromosome 17, 75840236: 75840236
40 UNC13D NM_199242.2(UNC13D): c.847A> G (p.Ile283Val) single nucleotide variant Benign rs61754871 GRCh37 Chromosome 17, 73836317: 73836317
41 UNC13D NM_199242.2(UNC13D): c.279C> T (p.Pro93=) single nucleotide variant Likely benign rs3744007 GRCh38 Chromosome 17, 75843056: 75843056
42 UNC13D NM_199242.2(UNC13D): c.279C> T (p.Pro93=) single nucleotide variant Likely benign rs3744007 GRCh37 Chromosome 17, 73839137: 73839137
43 UNC13D NM_199242.2(UNC13D): c.175G> A (p.Ala59Thr) single nucleotide variant Benign rs9904366 GRCh38 Chromosome 17, 75843245: 75843245
44 UNC13D NM_199242.2(UNC13D): c.175G> A (p.Ala59Thr) single nucleotide variant Benign rs9904366 GRCh37 Chromosome 17, 73839326: 73839326
45 UNC13D NM_199242.2(UNC13D): c.154-19G> A single nucleotide variant Benign rs3744009 GRCh38 Chromosome 17, 75843285: 75843285
46 UNC13D NM_199242.2(UNC13D): c.154-19G> A single nucleotide variant Benign rs3744009 GRCh37 Chromosome 17, 73839366: 73839366
47 UNC13D NM_199242.2(UNC13D): c.99G> A (p.Pro33=) single nucleotide variant Conflicting interpretations of pathogenicity rs147886860 GRCh37 Chromosome 17, 73840320: 73840320
48 UNC13D NM_199242.2(UNC13D): c.99G> A (p.Pro33=) single nucleotide variant Conflicting interpretations of pathogenicity rs147886860 GRCh38 Chromosome 17, 75844239: 75844239
49 UNC13D NM_199242.2(UNC13D): c.24G> A (p.Pro8=) single nucleotide variant Conflicting interpretations of pathogenicity rs143320460 GRCh38 Chromosome 17, 75844314: 75844314
50 UNC13D NM_199242.2(UNC13D): c.24G> A (p.Pro8=) single nucleotide variant Conflicting interpretations of pathogenicity rs143320460 GRCh37 Chromosome 17, 73840395: 73840395

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 CDK7 CDK8
2 10.66 CDK7 CDK8
3 10.43 ANXA2 S100A10
4 9.74 ANXA2 S100A10

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 extrinsic component of plasma membrane GO:0019897 8.96 ANXA2 S100A10
2 Weibel-Palade body GO:0033093 8.62 UNC13D VWF

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 ANXA2 S100A10
2 positive regulation of substrate adhesion-dependent cell spreading GO:1900026 9.26 S100A10 UNC13D
3 positive regulation of binding GO:0051099 9.16 ANXA2 S100A10
4 vesicle budding from membrane GO:0006900 8.96 ANXA2 S100A10
5 membrane raft assembly GO:0001765 8.62 ANXA2 S100A10

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 9.7 ANXA2 ASCL1 CDK7 CDK8 GET4 RTL10
2 cyclin-dependent protein serine/threonine kinase activity GO:0004693 9.16 CDK7 CDK8
3 RNA polymerase II carboxy-terminal domain kinase activity GO:0008353 8.62 CDK7 CDK8

Sources for Hemophagocytic Lymphohistiocytosis, Familial, 3

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9 Cosmic
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17 ExPASy
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69 SNOMED-CT via HPO
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74 UMLS via Orphanet
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