Alt. symbols: Munc13-4

Approved name: unc-13 homolog D
Alt. names: unc-13 homolog D (C. elegans)

Location: 17q25.1: 75827225 - 75844785 (-)
Gene type: protein_coding, 21 transcripts.

Scores: LoFtool: 0.763000 | pLI: 0.00000000 | LOEUF: 0.773

HGNC: 23147

NCBI: 201294, RefSeq: NG_007266.1

Ensembl: ENSG00000092929.13

LRG_122 | Status: public

OMIM: 608897

Expression | ProteinAtlas

Munc13-4 is a member of the Munc13-like family of proteins. It is highly expressed in CTL, NK cells, and mast cells and it is involved in granule exocytosis. Once granules are tethered to the plasma membrane, a priming step is required to enable fusion of the granule membrane with the plasma membrane. In this priming step, granules interact with a docking complex composed of Munc18-2 and Syntaxin-11. Thus, Munc13-4 triggers the switch of syntaxin-11 from a closed to an open conformation enabling fusion.

Biallelic missense, nonsense, frameshift and deep intronic UNC13D mutations are associated with autosomal recessive familial Hemophagocytic lymphohistiocytosis (fHLH) type 3 [MIM:608898] (PMID: 32076423), though immune dysregulation may present in other ways prior to the onset of frank HLH/macrophage activation syndrome (MAS) (PMID: 32222431, 28848550). In terms of monoallelic phenotypes, emerging evidence suggests that heterozygous loss-of-function may predispose to either malignant or non-mali gnant lymphoproliferation. One study reported missense variants C112S, V781I, I848L and A995P associated with autoimmune lymphoproliferative syndrome (ALPS) susceptibility and reduced granule exocytosis on in vitro assay (PMID: 23840885), while another reported an association between UNC13D haploinsufficiency and increased risk for lymphoma (PMID: 30758854). Additionally, heterozygous missense variants in UNC13D (R156W and R587C) were associated with decreased platelet degranulation, increased bleeding tendencies and/or thrombocytopenia in one study (PMID: 28399723). [Load More]