Protein unc-13 homolog D (Munc13-4) (UNC13D)

Protein unc-13 homolog D, commonly known as Munc13-4, is a critical regulator of vesicle priming and exocytosis, particularly within the immune system [UniProt: Q70Z35]. It is encoded by the UNC13D gene and is essential for the release of cytotoxic granules from natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) [PubMed: 14555994]. By facilitating the transition of docked vesicles to a fusion-competent state, Munc13-4 enables the delivery of perforin and granzymes to target cells, a process vital for immune surveillance and the control of hyperinflammation [NCBI: 201294]. Mutations in the UNC13D gene lead to Familial Hemophagocytic Lymphohistiocytosis type 3 (FHL3), a life-threatening condition characterized by overactive but ineffective immune cells and systemic inflammation [OMIM: 608897]. While there are currently no approved small-molecule drugs that directly target Munc13-4, it is a primary focus for gene therapy approaches aimed at restoring functional protein expression in hematopoietic stem cells [PubMed: 24163353]. Understanding its role in platelet secretion also suggests potential implications in cardiovascular health and thrombosis [PubMed: 15657415]. Monitoring CD107a surface expression on NK cells serves as a functional biomarker for Munc13-4 activity and is used in the diagnosis of FHL3 [PubMed: 15123586]. Therapeutic challenges include the precise delivery of gene therapy to the hematopoietic compartment and the risk of insertional mutagenesis [PubMed: 24163353].

Other names

Munc13-4HLH3FHL3JBSUnc13 homolog D

Not applicable (no approved drugs)