RGD Reference Report - Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).

Authors: Feldmann, J  Callebaut, I  Raposo, G  Certain, S  Bacq, D  Dumont, C  Lambert, N  Ouachee-Chardin, M  Chedeville, G  Tamary, H  Minard-Colin, V  Vilmer, E  Blanche, S  Le Deist, F  Fischer, A  De Saint Basile, G 
Citation: Feldmann J, etal., Cell. 2003 Nov 14;115(4):461-73.
RGD ID: 1600451
Pubmed: PMID:14622600   (View Abstract at PubMed)

Secretion of cytolytic granules content at the immunological synapse is a highly regulated process essential for lymphocyte cytotoxicity. This process requires the rapid transfer of perforin containing lytic granules to the target cell interface, followed by their docking and fusion with the plasma membrane. Defective cytotoxicity characterizes a genetically heterogeneous condition named familial hemophagocytic lymphohistiocytosis (FHL), which can be associated with perforin deficiency. The locus of a perforin (+) FHL subtype (FHL3), observed in 10 patients, was mapped to 17q25. This region contains hMunc13-4, a member of the Munc13 family of proteins involved in vesicle priming function. HMunc13-4 mutations were shown to cause FHL3. HMunc13-4 deficiency results in defective cytolytic granule exocytosis, despite polarization of the secretory granules and docking with the plasma membrane. Expressed tagged hMunc13-4 localizes with cytotoxic granules at the immunological synapse. HMunc13-4 is therefore essential for the priming step of cytolytic granules secretion preceding vesicle membrane fusion.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
UNC13DHumanfamilial hemophagocytic lymphohistiocytosis 3 susceptibilityIAGP DNA:deletions more ...RGD 
Unc13dRatfamilial hemophagocytic lymphohistiocytosis 3 susceptibilityISOUNC13D (Homo sapiens)DNA:deletions more ...RGD 
Unc13dMousefamilial hemophagocytic lymphohistiocytosis 3 susceptibilityISOUNC13D (Homo sapiens)DNA:deletions more ...RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
UNC13DHumanDecreased liver function susceptibilityIAGP DNA:deletions more ...RGD 
UNC13DHumanHepatosplenomegaly susceptibilityIAGP DNA:deletions more ...RGD 
UNC13DHumanHypertriglyceridemia susceptibilityIAGP DNA:deletions more ...RGD 
UNC13DHumanHypofibrinogenemia susceptibilityIAGP DNA:deletions more ...RGD 
UNC13DHumanPancytopenia susceptibilityIAGP DNA:deletions more ...RGD 
Objects Annotated

Genes (Rattus norvegicus)
Unc13d  (unc-13 homolog D)

Genes (Mus musculus)
Unc13d  (unc-13 homolog D)

Genes (Homo sapiens)
UNC13D  (unc-13 homolog D)


Additional Information