Affinage

UNC13D

Protein unc-13 homolog D · UniProt Q70J99

Length
1090 aa
Mass
123.3 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Munc13-4 (UNC13D) is a Ca2+-dependent vesicle tethering and priming factor that drives SNARE-mediated membrane fusion in regulated secretory and endolysosomal pathways across hematopoietic and non-hematopoietic cells (PMID:14622600, PMID:22508512). It is essential for the priming step of cytolytic granule secretion in cytotoxic lymphocytes that precedes membrane fusion, and loss-of-function mutations in UNC13D cause familial hemophagocytic lymphohistiocytosis type 3 (FHL3) (PMID:14622600). Munc13-4 senses Ca2+ through its tandem C2A and C2B domains: C2A supports Ca2+-stimulated SNARE binding while C2B drives Ca2+-dependent membrane binding, and together these domains enable Munc13-4 to promote Ca2+-triggered SNARE complex formation and SNARE-dependent liposome fusion (PMID:22508512, PMID:29884704). As a monomeric prolate ellipsoid able to bridge two membranes, it acts as a Ca2+-dependent tether that corrals motile secretory vesicles beneath the plasma membrane and clusters acidic-phospholipid membranes (PMID:26637270, PMID:21693760). Recruitment to target organelles occurs through direct binding to GTP-loaded Rab27a/Rab27b via a non-canonical N-terminal Rab27-binding motif, and through Rab11, linking Munc13-4 to dense-core granules, secretory lysosomes, and recycling endosomes (PMID:14699162, PMID:21693760, PMID:26637356). Beyond exocytosis, Munc13-4 binds the endosomal SNARE syntaxin 7 (and VAMP8) to govern late endosomal maturation and endosomal TLR signaling, a function pharmacologically validated as required for endosomal TLR3/7/9 responses (PMID:26680738, PMID:41942734). This broad fusion-machinery role underlies its requirement in cytotoxic lymphocyte killing, platelet dense/alpha-granule release and hemostasis, neutrophil granule exocytosis and phagosomal maturation, mast cell degranulation, Weibel-Palade body exocytosis, and tumor-associated exosomal PD-L1 secretion (PMID:20435885, PMID:23115246, PMID:28450451, PMID:41083534).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2003 High

    Established Munc13-4 as the priming factor whose loss causes a human immunodeficiency, defining its role in regulated secretion and placing it upstream of membrane fusion in cytotoxic granule exocytosis.

    Evidence Patient UNC13D mutation analysis, tagged-protein localization, and exocytosis assays in cytotoxic T lymphocytes

    PMID:14622600

    Open questions at the time
    • Molecular fusion mechanism not defined at this stage
    • No biochemical reconstitution of the priming activity
  2. 2003 High

    Identified Munc13-4 as the direct effector of GTP-Rab27, explaining how the secretory machinery is recruited to and activated at granules.

    Evidence Affinity purification, in vitro recombinant binding assay, and permeabilized platelet secretion rescue

    PMID:14699162

    Open questions at the time
    • Binding interface on Munc13-4 not mapped
    • Did not establish how Rab27 binding couples to fusion
  3. 2006 Medium

    Mapped specific Munc13-4 residues required for stable Rab27a complex formation, linking disease mutations to loss of effector binding.

    Evidence Mammalian two-hybrid analysis of the L403P missense mutant

    PMID:16278825

    Open questions at the time
    • Two-hybrid only; no structural or biophysical binding measurement
    • Functional secretion consequence not directly tested here
  4. 2008 High

    Extended Munc13-4 function beyond lymphocytes to neutrophil and mast cell granule exocytosis and identified Ca2+-regulated membrane recruitment and a Doc2alpha partner.

    Evidence Cell fractionation, immunofluorescence, siRNA/KO mouse cells, phospholipid binding, and reciprocal co-IP

    PMID:18354201 PMID:18453599 PMID:18939952

    Open questions at the time
    • Precise SNARE machinery engaged not yet defined
    • Relative contribution of Ca2+ vs Rab recruitment not resolved
  5. 2009 Medium

    Showed receptor-specific, Rab27a-dependent recruitment of Munc13-4 to lytic granules, revealing signal-dependent control of where the machinery assembles.

    Evidence Confocal colocalization in primary and patient-derived NK cells with defined receptor stimulation

    PMID:19704116

    Open questions at the time
    • Mechanism of differential receptor coupling unknown
    • Single-lab, imaging-based
  6. 2011 High

    Defined the Munc13-4-Rab27a complex as a tether that corrals motile secretory lysosomes at the plasma membrane and mapped a non-canonical Rab27a-binding motif required for degranulation.

    Evidence Rab27a-binding motif mutagenesis, FHL3 patient CTL complementation, mast cell rescue, and TIRF imaging; C-terminal C2B truncation analysis

    PMID:21693760 PMID:21755595

    Open questions at the time
    • Tethering vs priming activities not biochemically separated here
    • Structural basis of motif recognition not solved
  7. 2012 High

    Demonstrated biochemically that Munc13-4 is a Ca2+ sensor that promotes Ca2+-dependent SNARE complex formation and SNARE-mediated liposome fusion via its C2 domains, the first such priming factor activity reconstituted in vitro.

    Evidence In vitro Ca2+ binding, C2 Ca2+-residue mutagenesis, SNARE binding, liposome fusion reconstitution, and permeable cell exocytosis assays

    PMID:22508512

    Open questions at the time
    • Identity of physiological SNAREs at each compartment not fully resolved
    • Stoichiometry of fusion machinery not defined
  8. 2012 High

    Revealed Rab27a-independent Munc13-4 functions in phagosomal maturation/bacterial killing and PIP2/AP-2-dependent endocytic recycling needed to sustain serial killing.

    Evidence Munc13-4 KO mouse neutrophils with Rab27a KO comparison; PIP5K-gamma silencing, raft fractionation, and serial killing assays

    PMID:22271450 PMID:23115246

    Open questions at the time
    • How Munc13-4 is recruited independently of Rab27a not defined
    • Recycling-pathway role rests on single-lab Medium evidence
  9. 2013 Medium

    Established genetic epistasis placing Munc13-4 downstream of Rab27b (not only Rab27a) in mast cell degranulation.

    Evidence Multiple KO mouse BMMC models with double-knockout degranulation assays

    PMID:23281710

    Open questions at the time
    • Tissue-specific Rab27 isoform preference mechanism unclear
    • Single study
  10. 2014 High

    Defined transcriptional control of UNC13D through an intronic enhancer/alternative promoter, showing how non-coding disease variants reduce Munc13-4 expression.

    Evidence EMSA, ChIP, reporter assays, and patient PBMC qPCR identifying ELF1/STAT4/BRG1 regulation and the c.118-308C>T variant; complementary Rab27a-side interaction mapping

    PMID:24842371 PMID:25312756

    Open questions at the time
    • Full set of regulatory inputs not enumerated
    • Rab27a-side mapping is Medium-confidence patient-mutation work
  11. 2015 High

    Expanded the partner repertoire to Rab11 and the endosomal SNARE syntaxin 7/VAMP8, establishing Munc13-4 roles in recycling-endosome trafficking and late endosomal maturation distinct from classical exocytosis.

    Evidence TR-FRET/co-IP binding, super-resolution and live-cell imaging, KO neutrophils, Ca2+-binding and STX7-binding mutant rescue; AUC and proteoliposome fusion

    PMID:26637270 PMID:26637356 PMID:26680738

    Open questions at the time
    • How a single Munc13-4 selects among Rab11/Rab27/SNARE partners not resolved
    • Structural basis of monomeric membrane bridging inferred from AUC dimensions
  12. 2016 Medium

    Identified a Rab27-Munc13-4-Rab37 ternary complex through which Rab37 negatively regulates degranulation, adding a brake to the priming machinery.

    Evidence Co-IP, siRNA epistasis, and degranulation assays in RBL-2H3 cells

    PMID:26931073

    Open questions at the time
    • GTP-independent Rab37 binding mechanism unexplained
    • Single-lab
  13. 2017 High

    Showed Munc13-4 catalyzes both heterotypic granule-plasma membrane and homotypic granule-granule fusion and engages late endosomal SNARE complexes, broadening its fusion-machinery role; also defined it as a Weibel-Palade body tether in endothelium.

    Evidence Liposome fusion with exocytic and endosomal Q-SNAREs, Ca2+-binding mutants, TIRF imaging; TIRF/co-IP and VWF secretion assays with S100A10

    PMID:28100639 PMID:28450451

    Open questions at the time
    • Recruitment determinants in endothelial cells (S100A10 role) Medium-confidence
    • Switch between homotypic and heterotypic fusion not mechanistically defined
  14. 2018 High

    Confirmed both C2 domains as functionally required Ca2+ sensors controlling fusion-pore Ca2+ sensitivity, and established Munc13-4 as a rate-limiting determinant of platelet-driven thrombosis and inflammation in vivo.

    Evidence C2A/C2B aspartate mutagenesis with single-granule TIRF and cytotoxicity in NK cells; platelet-specific conditional KO with thrombosis, bleeding, and airway inflammation models

    PMID:29674495 PMID:29884704

    Open questions at the time
    • Quantitative Ca2+-sensing model across cell types incomplete
    • Indirect alpha-granule effect mechanism not resolved
  15. 2018 Medium

    Extended UNC13D dysregulation to additional non-coding disease variants and to autocrine TNF production in mast cells.

    Evidence EMSA/enhancer reporter and patient PBMC analysis of the NF-kB-disrupting c.117+143A>G variant; KO/rescue and TNF receptor antagonist in RBL-2H3 cells

    PMID:29409136 PMID:31897916

    Open questions at the time
    • How a secretion factor controls cytokine production not mechanistically defined
    • Single-lab studies
  16. 2019 Medium

    Linked Munc13-4 endosomal function to autophagy regulation via a TFEB-dependent program, connecting endolysosomal trafficking to lysosomal biogenesis.

    Evidence KO cells with WT vs STX7-binding-mutant rescue, autophagy flux assays, TFEB knockdown, and a cystinosis cell model

    PMID:30892133

    Open questions at the time
    • Direct vs indirect link to TFEB unresolved
    • Single-lab
  17. 2020 Medium

    Resolved the functional significance of UNC13D isoforms, showing the alternative N-terminal isoform is interchangeable for localization and exocytic rescue.

    Evidence Isoform-specific antibodies and FHL3 patient T cell complementation

    PMID:32582217

    Open questions at the time
    • Possible isoform-specific functions outside exocytosis untested
    • Single-lab
  18. 2018 High

    Demonstrated a Munc13-4-dependent Ca2+-stimulated exosome release pathway controlling MVB biogenesis and tumor matrix degradation through Rab11-dependent trafficking.

    Evidence siRNA knockdown, Ca2+-binding mutant rescue, CD63-pHluorin imaging, MVB morphology, MT1-MMP trafficking and ECM degradation assays

    PMID:29930202

    Open questions at the time
    • How Munc13-4 directs MVB-versus-secretory fates not defined
    • Cancer-cell specificity of the pathway not established
  19. 2022 Medium

    Uncovered a non-secretory regulatory role at the ER, where UNC13D restrains STING oligomerization and DNA-sensing innate immune signaling.

    Evidence Co-localization, co-IP/domain mapping, KO/KD cells, IFN-beta readouts, and STING inhibitor rescue

    PMID:36125406

    Open questions at the time
    • How a fusion factor localizes to ER and inhibits STING unclear
    • Single-lab
  20. 2024 Medium

    Defined a RAB11-UNC13D-FAK axis coupling recycling-endosome exocytosis to focal adhesion turnover and cancer cell migration.

    Evidence Co-IP/FERM-domain mapping, Ca2+-dependent FAK phosphorylation, and migration assays

    PMID:39210440

    Open questions at the time
    • Direct FAK interaction needs structural validation
    • Single-lab
  21. 2025 High

    Provided structural insight into the Munc13-4-Rab27a complex and defined a Munc13-4-PD-L1-HRS ternary complex driving exosomal PD-L1 secretion and immune evasion, validated by a disruptive peptide.

    Evidence Cryo-EM of Munc13-4-Rab27a, ternary co-IP, tumor-cell deletion, exosome PD-L1 assays, peptide inhibition, and in vivo tumor models

    PMID:41083534

    Open questions at the time
    • Atomic interface of PD-L1/HRS engagement not resolved
    • Generality across tumor types untested
  22. 2025 Medium

    Implicated Munc13-4 as a central regulator of crinophagy via secretory granule-lysosome fusion in endocrine cells.

    Evidence siRNA screen with live-cell SG-lysosome merge assay and Ca2+ manipulation (preprint)

    PMID:40951263

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Direct binding to the identified HOPS/SNARE machinery not biochemically shown
  23. 2026 High

    Pharmacologically validated the Munc13-4-STX7 interaction as mechanistically required for endolysosomal flux and endosomal TLR signaling, establishing it as a druggable inflammatory node.

    Evidence Small-molecule (ENDOtollin) inhibitors, endolysosomal flux and TLR signaling assays, and an in vivo CpG inflammation model

    PMID:41942734

    Open questions at the time
    • Selectivity of Munc13-4-STX7 disruption versus other SNARE interactions not fully mapped
    • Long-term consequences of chronic inhibition unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single Munc13-4 protein integrates competing Rab (Rab27a/b, Rab11, Rab37) and SNARE (exocytic vs syntaxin 7/VAMP8) partners to select among exocytosis, endosomal maturation, autophagy, and ER-based STING regulation in a cell-type- and signal-specific manner remains unresolved.
  • No unified structural/biophysical model of partner selection
  • Mechanism of compartment-specific recruitment incompletely defined
  • Non-secretory ER/STING role mechanistically isolated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140299 molecular sensor activity 3
Localization
GO:0005764 lysosome 3 GO:0005768 endosome 3 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 3 R-HSA-109582 Hemostasis 2 R-HSA-9612973 Autophagy 1
Partners
DOC2APTK2RAB11ARAB27ARAB27BSTING1STX7VAMP8
Complex memberships
Munc13-4-PD-L1-HRS complexMunc13-4-Rab27a complexRAB11-UNC13D-FAK complexRab27-Munc13-4-Rab37 ternary complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Munc13-4 (hMunc13-4) is essential for the priming step of cytolytic granule secretion preceding vesicle membrane fusion in cytotoxic T lymphocytes. Mutations in UNC13D cause FHL3. Deficiency results in defective cytolytic granule exocytosis despite normal polarization and docking of granules to the plasma membrane. Expressed tagged hMunc13-4 localizes with cytotoxic granules at the immunological synapse. Patient mutation analysis, subcellular localization of tagged protein (fluorescence microscopy), functional exocytosis assay in patient cells Cell High 14622600
2003 Munc13-4 is a GTP-Rab27A- and Rab27B-binding protein in platelets. Recombinant Munc13-4 directly binds GTP-Rab27A and Rab27B in vitro but not other GTPases, and enhances dense core granule secretion in a permeabilized platelet assay. Inhibition of secretion by unprenylated Rab27A was rescued by addition of Munc13-4, demonstrating that Munc13-4 mediates the effector function of GTP-Rab27. Affinity purification, in vitro binding assay (recombinant proteins), permeabilized platelet secretion assay with rescue experiment The Journal of biological chemistry High 14699162
2006 Missense mutation Leu403Pro in hMunc13-4 prevents formation of a stable hMunc13-4/Rab27a complex in vitro, demonstrating that specific residues in Munc13-4 are required for Rab27a interaction. Mammalian two-hybrid system (functional protein interaction assay in vitro) Human mutation Medium 16278825
2008 In human neutrophils, Munc13-4 is mainly cytosolic at rest and is rapidly recruited to membranes following fMLF stimulation in a Ca2+-dependent manner. A pool of Munc13-4 associated with secondary and tertiary granules is relocalized to the plasma membrane after fMLF stimulation. C2 domains of Munc13-4 bind phospholipid vesicles in a Ca2+-independent manner. Knockdown of Munc13-4 decreases tertiary granule exocytosis; overexpression enhances MMP-9 secretion. Cell fractionation, immunofluorescence, siRNA knockdown, phospholipid binding assay, secretion ELISA Journal of immunology Medium 18453599
2008 Doc2alpha co-localizes with Munc13-4 on secretory lysosomes in mast cells and interacts with Munc13-4 through two regions: the N-terminus (containing the Munc13-1-interacting domain) and the C-terminus (C2B domain). This Doc2alpha–Munc13-4 complex regulates Ca2+-dependent secretory lysosome exocytosis; mutations in either binding region or Doc2alpha knockdown impair exocytosis, rescued by Munc13-4 coexpression. Co-immunoprecipitation, co-localization (confocal microscopy), dominant-negative mutant expression, siRNA knockdown, rescue experiment, knockout mouse BMMC assay Journal of immunology High 18354201
2008 Munc13-4 regulates exocytosis of multiple neutrophil granule subsets (gelatinase/tertiary granules). Munc13-4 localizes at secretory organelles in neutrophils. Using Munc13-4-deficient (Jinx) mouse neutrophils, Munc13-4 was shown to be required for exocytosis of various secretory organelles, though CD11b mobilization was not affected. siRNA, total internal reflection fluorescence microscopy, Unc13d(Jinx) knockout mouse neutrophils, granule secretion assays Traffic High 18939952
2009 Munc13-4 and Rab27a are recruited to lytic granules in a stimulus-dependent manner in NK cells, but different receptor signals preferentially recruit Rab27a vs. Munc13-4: NKG2D and LFA-1 engagement induced Rab27a but not Munc13-4 colocalization with perforin, while CD16 (ADCC receptor) engagement induced Munc13-4 but not Rab27a colocalization. Colocalization of Munc13-4 with perforin was Rab27a-dependent. Immunofluorescence confocal microscopy of primary NK cells, receptor-specific stimulation, patient cells (Rab27a- and Munc13-4-deficient) Blood Medium 19704116
2010 Munc13-4 is a limiting factor in platelet secretion and hemostasis. Unc13d(Jinx) platelets lack Munc13-4 and show complete ablation of dense granule release and severe impairment of alpha-granule and lysosome secretion, reduced aggregation, and prolonged tail-bleeding times. The secretion defect is not due to altered SNARE expression or granule biogenesis. Recombinant Munc13-4 added to permeabilized Unc13d(Jinx) platelets rescues secretion. Munc13-4 levels directly correlate with extent of granule release. Unc13d(Jinx) mouse platelets, granule secretion assays, rescue with recombinant protein in permeabilized cells, tail bleeding time, aggregometry Blood High 20435885
2011 The Munc13-4–Rab27a complex is specifically required for tethering secretory lysosomes at the plasma membrane during degranulation. A non-canonical Rab27a-binding motif in the N-terminus of Munc13-4 was identified; point mutants impairing Rab27a binding fail to rescue degranulation in FHL3 patient CTLs and mast cells silenced for Munc13-4. TIRF microscopy revealed that the complex corrals motile secretory lysosomes beneath the plasma membrane; loss of Rab27a binding abolishes this tethering/docking function while not affecting secretory lysosome maturation. Mutagenesis of Rab27a-binding motif, complementation assay in FHL3 patient CTLs, mast cell siRNA knockdown, TIRF microscopy Blood High 21693760
2012 Munc13-4 binds Ca2+ through its C2A and C2B domains and reconstitutes Ca2+-dependent granule exocytosis in permeable cells (platelets, mast, and neuroendocrine cells) dependent on putative Ca2+-binding residues in both C2A and C2B. Munc13-4 exhibits Ca2+-stimulated SNARE interactions dependent on C2A, and Ca2+-dependent membrane binding dependent on C2B. Munc13-4 stimulates SNARE-dependent liposome fusion in a Ca2+- and C2 domain-dependent manner. Munc13-4 is the first priming factor shown to promote Ca2+-dependent SNARE complex formation and SNARE-mediated liposome fusion. In vitro Ca2+ binding assay, permeable cell exocytosis assay with mutagenesis of Ca2+-binding residues, SNARE binding assay, liposome fusion reconstitution assay The Journal of cell biology High 22508512
2012 MUNC13-4 is essential for phagosomal maturation and bacterial killing in neutrophils. MUNC13-4-deficient (KO) mouse neutrophils show impaired p22phox-expressing granule trafficking to the plasma membrane, defective extracellular and intracellular ROS production, impaired delivery of azurophilic granules and multivesicular bodies to the phagosome, and markedly impaired intracellular killing of P. aeruginosa. This phagosomal maturation function is RAB27A-independent. Munc13-4 KO mouse neutrophils, vesicle trafficking assays, ROS measurement, bacterial killing assay, comparison with Rab27a KO The Journal of biological chemistry High 23115246
2012 PIP2 regulates Munc13-4 compartmentalization in NK cells. Granule secretion triggering induces transient Munc13-4 raft recruitment followed by AP-2/clathrin-dependent internalization. PIP5K-gamma silencing impairs granule secretion with increased raft-associated Munc13-4 due to defective AP-2 recruitment, impairing Munc13-4 reinternalization. This Munc13-4 endocytic recycling is required to maintain an intracellular pool necessary for serial NK cell killing. siRNA silencing of PIP5K-gamma, biochemical fractionation (membrane raft isolation), co-immunoprecipitation, serial killing assay in primary NK cells Blood Medium 22271450
2013 In mast cells, Rab27b (not Rab27a) acts as a positive regulator of degranulation through its effector Munc13-4. Munc13-4-deficient (Jinx) BMMCs phenocopy Rab27b KO and Rab27a/b double-KO secretory impairment, consistent with Munc13-4 acting downstream of Rab27b in granule exocytosis. Knockout mouse BMMCs (Rab27a ashen, Rab27b KO, Munc13-4 Jinx, double KO), degranulation assays, pharmacological actin disruption The FEBS journal Medium 23281710
2014 Transcription of UNC13D in cytotoxic lymphocytes is regulated by an intronic enhancer/alternative promoter in intron 1. The FHL3-associated mutation c.118-308C>T disrupts binding of the ETS family transcription factor ELF1 to this conserved intronic sequence, impairing STAT4 and BRG1 (chromatin remodeling complex) recruitment, reducing active histone modifications and diminishing Munc13-4 expression. TCR engagement facilitates STAT4-dependent Munc13-4 expression in naive CD8+ T cells. Electrophoretic mobility shift assay, chromatin immunoprecipitation, reporter assay, quantitative PCR in patient PBMCs, histone modification analysis The Journal of experimental medicine High 24842371
2014 Rab27a mutations at residues R141, Y159, and S163 selectively disrupt Rab27a interaction with Munc13-4 without impairing Rab27a–melanophilin interaction, identifying a critical binding site for Munc13-4 on Rab27a. Patient mutation analysis, functional interaction assays in patient cells, protein interaction studies The Journal of allergy and clinical immunology Medium 25312756
2015 Munc13-4 binds Rab11a (but not dominant-negative Rab11a) and regulates trafficking and docking of Rab11-positive vesicles at the plasma membrane in neutrophils. A Ca2+-binding-deficient Munc13-4 mutant significantly impairs Rab11 trafficking. Munc13-4-deficient neutrophils show normal endocytosis but impaired Rab11-vesicle trafficking, up-regulation, and retention at the plasma membrane, correlating with deficient NADPH oxidase activation. TR-FRET binding assay, co-immunoprecipitation, super-resolution microscopy, vesicular dynamics analysis, Munc13-4 KO mouse neutrophils, Ca2+-binding mutant expression The Journal of biological chemistry High 26637356
2015 Munc13-4 acts as a Ca2+-dependent tether during platelet secretion. Ca2+-dependent enhancement of SNARE-dependent proteoliposome fusion requires both C2 domains of Munc13-4 and the Ca2+-coordinating aspartate residues of C2B specifically. Munc13-4 clusters PS-containing liposomes in response to Ca2+. Analytical ultracentrifugation shows Munc13-4 is a monomeric prolate ellipsoid with dimensions compatible with bridging two fusing membranes. Dense granules are highly mobile in Munc13-4-null platelets at rest and during stimulation with no stimulation-dependent release, indicating Munc13-4 plays a vesicle-stabilizing/tethering role. In vitro SNARE-dependent proteoliposome fusion assay, mutagenesis of C2 domain Ca2+-liganding residues, liposome clustering assay, analytical ultracentrifugation, live-cell mepacrine dense granule imaging in Unc13d(Jinx) platelets The Biochemical journal High 26637270
2015 Munc13-4 interacts with syntaxin 7 (STX7) and VAMP8, with Ca2+ significantly increasing Munc13-4–STX7 binding. A STX7-binding-deficient Munc13-4 mutant fails to rescue late endosomal maturation defects in Munc13-4-deficient cells. Munc13-4 regulates late endosomal maturation: its deficiency causes enlarged late endosomes and decreased degradative capacity. Munc13-4-KO neutrophils show impaired TLR9-dependent signaling and CD11b up-regulation. Co-immunoprecipitation, high-resolution and live-cell microscopy, rescue assay with STX7-binding-deficient mutant, late endosome size/function quantification, TLR9 signaling assay in KO neutrophils Molecular biology of the cell High 26680738
2016 Rab37, a small GTPase present on mast cell secretory granules, binds Munc13-4 in a GTP-independent manner and forms a Rab27–Munc13-4–Rab37 ternary complex. Rab37 negatively regulates mast cell degranulation; Rab37 knockdown causes hypersecretion that is suppressed by co-knockdown of Rab27a/b or Munc13-4, indicating Rab37 acts through the Rab27–Munc13-4 system. co-immunoprecipitation, siRNA knockdown, dominant-active mutant overexpression, degranulation assay in RBL-2H3 cells Scientific reports Medium 26931073
2017 Munc13-4 functions as a tethering/priming factor and Ca2+ sensor for both heterotypic secretory granule (SG)–plasma membrane and homotypic SG–SG fusion in mast cells. Ca2+ stimulation generates large Munc13-4+/Rab7+/Rab11+ endosomal vacuoles through homotypic SG fusion, dependent on Ca2+ binding to Munc13-4. Munc13-4 promotes Ca2+-stimulated fusion of VAMP8-containing liposomes with both exocytic and endosomal Q-SNARE liposomes, and directly interacts with late endosomal SNARE complexes. Vacuoles are exocytic and mediate secretion. Ca2+ stimulation live-cell imaging, TIRF microscopy, liposome fusion assay with VAMP8-containing and Q-SNARE liposomes, Ca2+-binding mutants, SNARE co-precipitation Molecular biology of the cell High 28100639
2017 Munc13-4 is a Weibel-Palade body (WPB) tethering factor in endothelial cells. Munc13-4 is present on WPBs and its secretagogue-evoked recruitment to WPBs is increased at sites of WPB–plasma membrane contact. Munc13-4 promotes histamine-evoked WPB exocytosis. The S100A10 subunit of the annexin A2–S100A10 complex is a novel Munc13-4 interactor that participates in recruiting Munc13-4 to WPB fusion sites. Fluorescence microscopy (TIRF), co-immunoprecipitation, siRNA knockdown, von Willebrand factor secretion assay in endothelial cells Molecular biology of the cell Medium 28450451
2018 Munc13-4 regulates a Ca2+-stimulated exosome release pathway in cancer cells. Munc13-4 knockdown eliminates Ca2+-triggered CD63+/CD9+/ALIX+ exosome release; Ca2+-binding-deficient Munc13-4 mutants fail to restore this release. Munc13-4 depletion reduces the size of CD63+ multivesicular bodies (MVBs) in breast carcinoma cells. Munc13-4 uses a Rab11-dependent trafficking pathway to generate MVBs competent for exosome release. Munc13-4 depletion reduces MT1-MMP trafficking to MVBs and extracellular matrix degradation. siRNA knockdown, Ca2+-binding-deficient mutant rescue, CD63-pHluorin live imaging, MVB size quantification, MT1-MMP trafficking assay, ECM degradation assay The Journal of cell biology High 29930202
2018 Both C2 domains of Munc13-4 are critical Ca2+ sensors for NK cell degranulation and cytotoxicity. Point mutations in aspartate residues in either C2A or C2B diminish exocytosis, alter Ca2+ sensitivity of fusion pore opening, and impair NK cell cytotoxicity against malignant cells. TIRF microscopy showed these mutations alter Ca2+ dependence and frequency of single-granule fusion events. Site-directed mutagenesis of C2A/C2B Ca2+-coordinating aspartates, expression in primary mouse NK cells and RBL mast cells, TIRF single-granule imaging, cytotoxicity assay Journal of immunology High 29884704
2018 Platelet-specific deletion of Munc13-4 ablates dense granule release and indirectly impairs alpha-granule exocytosis (Munc13-2 has no exocytic role in platelets even in absence of Munc13-4). Munc13-4 acts as a rate-limiting factor in thrombus formation in vitro and in vivo. Munc13-4 expression in platelets dose-dependently regulates venous bleeding time and arterial thrombosis. Platelet-specific Munc13-4 KO reduces airway hyper-responsiveness and eosinophilic inflammation in allergic model. Conditional Munc13-4 KO mice (platelet-specific), granule secretion assays, flow chamber thrombosis assay, in vivo bleeding and thrombosis models, airway inflammation model Haematologica High 29674495
2018 An intronic UNC13D variant (c.117+143A>G) disrupts NF-κB binding to a functional transcriptional enhancer in intron 1, reducing UNC13D transcript levels in patient PBMCs and impairing NK cell degranulation. This was demonstrated by EMSA showing disrupted NF-κB binding and in vitro transcriptional enhancer assay showing reduced activity. EMSA, in vitro transcriptional enhancer assay, qPCR of patient PBMCs, NK cell degranulation assay, partial UNC13D knockdown Arthritis & rheumatology Medium 29409136
2019 UNC13D-deficient cells show impaired endosomal trafficking, defective endocytic flux, and increased autophagic flux. The defective endosomal phenotype is rescued by UNC13D but not by its STX7-binding-deficient mutant. The increased autophagy in UNC13D-deficient cells is driven at least in part by TFEB-mediated upregulation of autophagic and lysosomal genes including Atg9b; TFEB knockdown reduces Atg9b and autophagy. UNC13D upregulation corrects endolysosomal trafficking and reduces autophagosome accumulation in a cystinosis cell model. KO cells, rescue with WT vs. STX7-binding mutant, autophagy flux assays, TFEB knockdown, biochemical and microscopy methods, cystinosis cell model Autophagy Medium 30892133
2020 UNC13D encodes two isoforms with distinct N-termini driven by an alternative promoter/TSS in intron 1. The alternative (lymphocyte/platelet-predominant) isoform has a unique N-terminus but does not differ from the conventional isoform in Munc13-4 localization, trafficking to the immunological synapse, or ability to restore exocytosis in FHL3 patient T cells. Both isoforms equivalently rescue degranulation. Isoform-specific antibodies, subcellular localization (imaging), complementation/rescue assay in FHL3 patient T cells, ectopic expression Frontiers in immunology Medium 32582217
2022 UNC13D co-localizes with STING on the endoplasmic reticulum and inhibits STING oligomerization. Knockdown or knockout of UNC13D promotes IFN-β production in response to DNA viruses (but not RNA viruses) and increases basal proinflammatory cytokine levels, effects abolished by a STING inhibitor. The domains on both UNC13D and STING mediating their interaction were mapped. Co-localization (fluorescence microscopy), co-immunoprecipitation/interaction mapping, UNC13D knockdown and knockout, IFN-β reporter/ELISA, STING inhibitor rescue EMBO reports Medium 36125406
2024 UNC13D regulates pancreatic cancer cell migration by coupling exocytosis of recycling endosomes with focal adhesion turnover through the RAB11–UNC13D–FAK axis. UNC13D directly interacts with the FERM domain of FAK and regulates FAK phosphorylation in a calcium-dependent manner. Immunoprecipitation confirmed the RAB11–UNC13D–FAK complex in endosomes during integrin recycling. Co-immunoprecipitation, immunocytochemistry, migration assays, FAK phosphorylation assay, domain interaction mapping (FERM domain) Journal of translational medicine Medium 39210440
2025 Munc13-4 collaborates with HRS, Rab27, and SNAREs to facilitate PD-L1 sorting and secretion via exosomes in tumor cells, mediating immune evasion. PD-L1 sorting relies on a ternary Munc13-4–PD-L1–HRS complex regulated by IFNγ signaling. Cryo-EM analysis of the Munc13-4–Rab27a complex provided structural insights into exosome secretion. A designed peptide disrupting the Munc13-4–PD-L1 interaction inhibits PD-L1 exosomal sorting and enhances anti-tumor immunity. Cryo-EM structure of Munc13-4–Rab27a complex, co-immunoprecipitation (ternary complex), Munc13-4 deletion in tumor cells, exosome PD-L1 assay, designed peptide inhibition, in vivo tumor models Nature communications High 41083534
2025 Munc13-4 is a central regulator of crinophagy (secretory granule–lysosome fusion) in mammalian endocrine cells. siRNA screening identified Munc13-4 as required for SG-lysosome merge along with Rab27A, VAMP2, PLEKHM1, HOPS subunits, and SNAREs STX7, STX8, VTI1B. SG-lysosome fusion is regulated by local or global calcium through binding and activation of Munc13-4. siRNA screen with live-cell SG-lysosome merge assay, Ca2+ manipulation, identification of required components Research square (preprint)preprint Medium 40951263
2026 Small-molecule ENDOtollins (ENDOs) that inhibit the Munc13-4–STX7 interaction reduce endolysosomal flux, impair endosomal TLR3/7/9 signaling in dendritic cells and ERK signaling in neutrophils in response to endosomal (but not plasma membrane) TLR ligands, and reduce CpG-induced systemic inflammation in vivo. This establishes the Munc13-4–STX7 interaction as mechanistically required for endosomal TLR signaling. High-throughput compound screen, orthogonal cell-based validation, endolysosomal flux assay, TLR signaling assays, in vivo CpG inflammation model, chemical optimization Nature chemical biology High 41942734
2011 A C-terminal C2B domain truncation mutation in Munc13-4 (p.Arg899X; Munc13-4(1-899)) correctly targets to CD63+ secretory lysosomes but shows reduced stability, uncoupled dynamic turnover on granule membrane, and fails to rescue degranulation in cells with silenced endogenous Munc13-4. This demonstrates that the C-terminal C2B domain is essential for Munc13-4 function. Ectopic expression of truncation mutant in patient/silenced cells, CD63 co-localization, protein stability assay, degranulation rescue assay Pediatric blood & cancer Medium 21755595
2018 In airway epithelial cells, Munc13-4 (but not Munc13-2) is specifically recruited to the plasma membrane and increases its interaction with syntaxin 2 in response to human neutrophil elastase (hNE) stimulation. Munc13-4 siRNA knockdown reduces hNE-stimulated MUC5AC secretion while increasing intracellular MUC5AC retention, indicating Munc13-4 mediates hNE-stimulated airway mucin hypersecretion via syntaxin 2. Co-immunoprecipitation (Munc13-4–syntaxin 2), siRNA knockdown, ELISA for MUC5AC secretion, immunofluorescence, Western blotting Molecular medicine reports Low 29767240
2020 Munc13-4 is required for TNF production (not just secretion) in activated RBL-2H3 mast cells. Munc13-4 KO cells show absent antigen/IgE-induced TNF production, restored by Munc13-4 re-expression. A TNF receptor antagonist blocks TNF production without inhibiting release, revealing a TNF autocrine feed-back loop that requires Munc13-4. Munc13-4 KO cell line, rescue by re-expression, ELISA for TNF secretion and intracellular levels, TNF receptor antagonist Inflammation Medium 31897916

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell 694 14622600
2011 Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood 321 21881043
2006 Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Human mutation 225 16278825
2018 A Ca2+-stimulated exosome release pathway in cancer cells is regulated by Munc13-4. The Journal of cell biology 191 29930202
2003 Munc13-4 is a GTP-Rab27-binding protein regulating dense core granule secretion in platelets. The Journal of biological chemistry 163 14699162
2007 Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. The Journal of experimental medicine 148 17420270
2008 Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms. Arthritis and rheumatism 141 18759271
2006 Analysis of natural killer-cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD107a surface expression heralds Munc13-4 defect and discriminates between genetic subtypes of the disease. Blood 137 16778144
2010 Munc13-4 is a limiting factor in the pathway required for platelet granule release and hemostasis. Blood 105 20435885
2011 The munc13-4-rab27 complex is specifically required for tethering secretory lysosomes at the plasma membrane. Blood 104 21693760
2010 Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases. Haematologica 102 20823128
2011 Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) caused by deep intronic mutation and inversion in UNC13D. Blood 99 21931115
2009 Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity. Blood 85 19704116
2008 Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis. Arthritis and rheumatism 83 18240215
2012 Munc13-4 reconstitutes calcium-dependent SNARE-mediated membrane fusion. The Journal of cell biology 78 22508512
2008 Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis. British journal of haematology 73 18710388
2008 The Rab27a effectors JFC1/Slp1 and Munc13-4 regulate exocytosis of neutrophil granules. Traffic (Copenhagen, Denmark) 72 18939952
2006 Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. Journal of medical genetics 68 16825436
2013 Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion. The FEBS journal 62 23281710
2015 Munc13-4 Is a Rab11-binding Protein That Regulates Rab11-positive Vesicle Trafficking and Docking at the Plasma Membrane. The Journal of biological chemistry 60 26637356
2008 Munc13-4 regulates granule secretion in human neutrophils. Journal of immunology (Baltimore, Md. : 1950) 58 18453599
2004 Identification of novel MUNC13-4 mutations in familial haemophagocytic lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T lymphocytes. Journal of medical genetics 53 15466010
2007 Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis. Journal of medical genetics 49 17993578
2009 UNC13D is the predominant causative gene with recurrent splicing mutations in Korean patients with familial hemophagocytic lymphohistiocytosis. Haematologica 47 20015888
2008 Doc2 alpha and Munc13-4 regulate Ca(2+) -dependent secretory lysosome exocytosis in mast cells. Journal of immunology (Baltimore, Md. : 1950) 47 18354201
2014 Patients with Griscelli syndrome and normal pigmentation identify RAB27A mutations that selectively disrupt MUNC13-4 binding. The Journal of allergy and clinical immunology 42 25312756
2017 A novel Munc13-4/S100A10/annexin A2 complex promotes Weibel-Palade body exocytosis in endothelial cells. Molecular biology of the cell 40 28450451
2018 Genetic variant spectrum in 265 Chinese patients with hemophagocytic lymphohistiocytosis: Molecular analyses of PRF1, UNC13D, STX11, STXBP2, SH2D1A, and XIAP. Clinical genetics 39 29665027
2011 Increased survival and reduced neutrophil infiltration of the liver in Rab27a- but not Munc13-4-deficient mice in lipopolysaccharide-induced systemic inflammation. Infection and immunity 39 21746860
2011 Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Pediatric blood & cancer 38 21674762
2018 Brief Report: Novel UNC13D Intronic Variant Disrupting an NF-κB Enhancer in a Patient With Recurrent Macrophage Activation Syndrome and Systemic Juvenile Idiopathic Arthritis. Arthritis & rheumatology (Hoboken, N.J.) 36 29409136
2012 Founder effects in two predominant intronic mutations of UNC13D, c.118-308C>T and c.754-1G>C underlie the unusual predominance of type 3 familial hemophagocytic lymphohistiocytosis (FHL3) in Korea. Annals of hematology 34 23180437
2011 Rapid diagnosis of FHL3 by flow cytometric detection of intraplatelet Munc13-4 protein. Blood 34 21653941
2015 Munc13-4 interacts with syntaxin 7 and regulates late endosomal maturation, endosomal signaling, and TLR9-initiated cellular responses. Molecular biology of the cell 33 26680738
2014 Transcriptional regulation of Munc13-4 expression in cytotoxic lymphocytes is disrupted by an intronic mutation associated with a primary immunodeficiency. The Journal of experimental medicine 33 24842371
2021 Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms. European journal of human genetics : EJHG 30 33867526
2014 The 253-kb inversion and deep intronic mutations in UNC13D are present in North American patients with familial hemophagocytic lymphohistiocytosis 3. Pediatric blood & cancer 30 24470399
2012 MUNC13-4 protein regulates the oxidative response and is essential for phagosomal maturation and bacterial killing in neutrophils. The Journal of biological chemistry 29 23115246
2019 Retroviral UNC13D Gene Transfer Restores Cytotoxic Activity of T Cells Derived from Familial Hemophagocytic Lymphohistiocytosis Type 3 Patients In Vitro. Human gene therapy 27 31032638
2012 PIP2-dependent regulation of Munc13-4 endocytic recycling: impact on the cytolytic secretory pathway. Blood 27 22271450
2013 Variations of the UNC13D gene in patients with autoimmune lymphoproliferative syndrome. PloS one 26 23840885
2016 Mast cell degranulation is negatively regulated by the Munc13-4-binding small-guanosine triphosphatase Rab37. Scientific reports 25 26931073
2015 Role of Munc13-4 as a Ca2+-dependent tether during platelet secretion. The Biochemical journal 25 26637270
2017 Munc13-4 functions as a Ca2+ sensor for homotypic secretory granule fusion to generate endosomal exocytic vacuoles. Molecular biology of the cell 24 28100639
2017 Gene transfer into hematopoietic stem cells reduces HLH manifestations in a murine model of Munc13-4 deficiency. Blood advances 23 29296930
2020 Lentiviral Gene Therapy for Familial Hemophagocytic Lymphohistiocytosis Type 3, Caused by UNC13D Genetic Defects. Human gene therapy 22 32253931
2020 Clinical, immunological and genetic findings in patients with UNC13D deficiency (FHL3): A systematic review. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 22 32679608
2010 Hemophagocytic lymphohistiocytosis with MUNC13-4 gene mutation or reduced natural killer cell function prior to onset of childhood leukemia. Pediatric blood & cancer 21 21370424
2006 Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism. Biochemical and biophysical research communications 20 16630545
2018 Platelet Munc13-4 regulates hemostasis, thrombosis and airway inflammation. Haematologica 18 29674495
2013 Mutation of FAS, XIAP, and UNC13D genes in a patient with a complex lymphoproliferative phenotype. Pediatrics 18 24043286
2022 UNC13D inhibits STING signaling by attenuating its oligomerization on the endoplasmic reticulum. EMBO reports 17 36125406
2015 Synergistic defects of UNC13D and AP3B1 leading to adult hemophagocytic lymphohistiocytosis. International journal of hematology 17 25980904
2011 Hemophagocytic lymphohistiocytosis with Munc13-4 mutation: a cause of recurrent fatal hydrops fetalis. Pediatrics 17 21646258
2019 Cross-regulation of defective endolysosome trafficking and enhanced autophagy through TFEB in UNC13D deficiency. Autophagy 16 30892133
2018 C2 Domains of Munc13-4 Are Crucial for Ca2+-Dependent Degranulation and Cytotoxicity in NK Cells. Journal of immunology (Baltimore, Md. : 1950) 16 29884704
2017 Late-Onset Non-HLH Presentations of Growth Arrest, Inflammatory Arachnoiditis, and Severe Infectious Mononucleosis, in Siblings with Hypomorphic Defects in UNC13D. Frontiers in immunology 16 28848550
2008 Fatal sibling cases of familial hemophagocytic lymphohistiocytosis (FHL) with MUNC13-4 mutations: case reports. Pediatric hematology and oncology 14 18432499
2019 Haploinsufficiency of UNC13D increases the risk of lymphoma. Cancer 13 30758854
2013 Novel mutations in the UNC13D gene carried by a Chinese neonate with hemophagocytic lymphohistiocytosis. Yonsei medical journal 13 23709445
2024 Recycling machinery of integrin coupled with focal adhesion turnover via RAB11-UNC13D-FAK axis for migration of pancreatic cancer cells. Journal of translational medicine 10 39210440
2021 Spectrum mutations of PRF1, UNC13D, STX11, and STXBP2 genes in Vietnamese patients with hemophagocytic lymphohistiocytosis. International journal of laboratory hematology 9 34339548
2015 Familial Hemophagocytic Lymphohistiocytosis due to Mutation of UNC13D Gene. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 9 27408432
2012 Munc13-4*rab27 complex tethers secretory lysosomes at the plasma membrane. Communicative & integrative biology 9 22482013
2006 Familial hemophagocytic lymphohistiocytosis with the MUNC13-4 mutation: a case report. European journal of pediatrics 9 16416131
2020 TNF Production in Activated RBL-2H3 Cells Requires Munc13-4. Inflammation 8 31897916
2020 Alternative UNC13D Promoter Encodes a Functional Munc13-4 Isoform Predominantly Expressed in Lymphocytes and Platelets. Frontiers in immunology 8 32582217
2018 Characterization of a large UNC13D gene duplication in a patient with familial hemophagocytic lymphohistiocytosis type 3. Clinical immunology (Orlando, Fla.) 8 29596912
2018 Synergistic defects of novo FAS and homozygous UNC13D leading to autoimmune lymphoproliferative syndrome-like disease: A 10-year-old Chinese boy case report. Gene 8 29864493
2014 Novel and atypical splicing mutation in a compound heterozygous UNC13D defect presenting in Familial Hemophagocytic Lymphohistiocytosis triggered by EBV infection. Clinical immunology (Orlando, Fla.) 8 24825797
2011 A novel Dutch mutation in UNC13D reveals an essential role of the C2B domain in munc13-4 function. Pediatric blood & cancer 8 21755595
2024 Functional role of UNC13D in immune diseases and its therapeutic applications. Frontiers in immunology 7 39469717
2018 Small molecules that inhibit the late stage of Munc13-4-dependent secretory granule exocytosis in mast cells. The Journal of biological chemistry 7 29615494
2017 Characterization of a novel splicing mutation in UNC13D gene through amplicon sequencing: a case report on HLH. BMC medical genetics 6 29157204
2014 Munc13-4 deficiency with CD5 downregulation on activated CD8+ T cells. Pediatrics international : official journal of the Japan Pediatric Society 6 25252047
2022 Familial Hemophagocytic Lymphohistiocytosis secondary to UNC13D mutation: a report of two cases. BMC pediatrics 5 36401200
2008 Methods for analysis of rab27a/Munc13-4 in secretory lysosome release in hematopoietic cells. Methods in enzymology 5 18413249
2025 UNC13D c.2588G>A Nucleotide Variant Impairs NK-Cell Cytotoxicity in Adult-Onset EBV-Associated Hemophagocytic Lymphohistiocytosis: A Pedigree Study. International journal of molecular sciences 4 40943599
2025 Munc13-4 mediates tumor immune evasion by regulating the sorting and secretion of PD-L1 via exosomes. Nature communications 4 41083534
2019 Analysis of Ca2+-Dependent Weibel-Palade Body Tethering by Live Cell TIRF Microscopy: Involvement of a Munc13-4/S100A10/Annexin A2 Complex. Methods in molecular biology (Clifton, N.J.) 4 30710289
2018 Munc13‑4 mediates human neutrophil elastase‑induced airway mucin5AC hypersecretion by interacting with syntaxin2. Molecular medicine reports 4 29767240
2018 Identification of a novel nonsense mutation in the UNC13D gene from a patient with hemophagocytic lymphohistiocytosis: a case report. BMC medical genetics 4 29783935
2014 Defective UNC13D gene-associated familial hemophagocytic lymphohistiocytosis triggered by visceral leishmaniasis: a diagnostic challenge. Journal of pediatric hematology/oncology 4 23774160
2019 Neonatal Cytomegalovirus Palatal Ulceration and Bocavirus Pneumonitis Associated With a Defect of Lymphocyte Cytotoxicity Caused by Mutations in UNC13D. Journal of the Pediatric Infectious Diseases Society 3 29415165
2015 A Hemophagocytic Lymphohistiocytosis Case with Newly Defined UNC13D (c.175G>C; p.Ala59Pro) Mutation and a Rare Complication. Turkish journal of haematology : official journal of Turkish Society of Haematology 3 26377049
2025 Investigation of a pathogenic inversion in UNC13D and comprehensive analysis of chromosomal inversions across diverse datasets. European journal of human genetics : EJHG 2 40021841
2024 Relapsed/Refractory Peripheral T-Cell Lymphoma-Associated Hemophagocytic Lymphohistiocytosis With UNC13D and CD27 Germline Mutations. Cell transplantation 2 38183241
2024 Detection of a novel gross deletion in the UNC13D gene ends the diagnostic odyssey for a family with familial hemophagocytic lymphohistiocytosis 3. BMC pediatrics 1 38212754
2019 Clinical and Genetic Analysis of Nine Suspected Familial Haemophagocytic Lymphohistiocytosis Patients for MUNC13-4 Deficiency and Introducing Four Novel Mutations in UNC13D. Iranian journal of allergy, asthma, and immunology 1 32245292
2026 Two Cases of CLIPPERS-like Syndrome Sharing a Hypomorphic UNC13D Variant. Journal of clinical immunology 0 41781714
2026 Genetic and clinical characteristics of 54 pediatric lymphoma patients with variant mutation sites of UNC13D. Haematologica 0 41784029
2026 Munc13-4-STX7 inhibitors impair endosomal TLR activation and systemic inflammation. Nature chemical biology 0 41942734
2026 UNC13D in Familial Hemophagocytic Lymphohistiocytosis and Beyond: Functional Mechanisms, Genetic Variants, Multisystem Disease Spectrum and Clinical Implications. Scandinavian journal of immunology 0 42032368
2025 Molecular Characterization and Expression of unc-13d in the Sex Reversal of Monopterus albus. Animals : an open access journal from MDPI 0 39858121
2025 Clinical and genetic features of UNC13D deficiency with hypogammaglobulinemia. Frontiers in immunology 0 40901478
2025 Molecular requirements for mammalian crinophagy highlight a key role for Ca2+-dependent Munc13-4. Research square 0 40951263
2025 Hemophagocytic lymphohistiocytosis caused by dual mutations in UNC13D and STX11 induced by HHV-7: a case report and review of the literature. Annals of hematology 0 41028446
2025 Human herpesvirus 6B infection in an adult with hemophagocytic lymphohistiocytosis carrying an UNC13D mutation: a case report and literature review. Frontiers in immunology 0 41394838
2024 Investigation of a Pathogenic Inversion in UNC13D and Comprehensive Analysis of Chromosomal Inversions Across Diverse Datasets. medRxiv : the preprint server for health sciences 0 39574843
2013 [Type III familial hemophagocytic lymphohistiocytosis susceptibility gene UNC13D involves in homologous recombination repair]. Zhongguo shi yan xue ye xue za zhi 0 23815924

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