Affinage

STXBP2

Syntaxin-binding protein 2 · UniProt Q15833

Length
593 aa
Mass
66.5 kDa
Annotated
2026-04-28
53 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STXBP2 (Munc18-2) is a Sec1/Munc18-family protein that functions as a master regulator of SNARE-mediated exocytosis in hematopoietic and epithelial cells by chaperoning cognate syntaxins to target membranes and directly promoting SNARE complex assembly to drive complete membrane fusion. It binds syntaxin 11 with high affinity in cytotoxic lymphocytes and platelets, where it is required for lytic granule and platelet granule exocytosis, and interacts with syntaxins 2 and 3 in mast cells and intestinal epithelial cells to control secretory granule translocation along microtubules and cargo-selective apical membrane trafficking (PMID:19804848, PMID:28265073, PMID:30696774, PMID:24323579, PMID:28724787). Biallelic loss-of-function mutations in STXBP2 cause familial hemophagocytic lymphohistiocytosis type 5 (FHL5), and specific missense mutations such as R65Q/W and R190C act in a dominant-negative manner by arresting late SNARE complex assembly without abolishing syntaxin binding (PMID:25564401, PMID:33162974). STXBP2 mutations also produce cell-intrinsic intestinal and renal epithelial trafficking defects recapitulating microvillus inclusion disease pathology, which persists after hematopoietic stem cell transplantation (PMID:23382066, PMID:30364784).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    Establishing STXBP2 as a syntaxin 3-binding regulator of polarized epithelial trafficking answered whether Sec1/Munc18 proteins operate beyond neurons—Munc18-2 bound syntaxin 3 and controlled apical delivery in intestinal epithelial cells, with point mutants revealing both syntaxin-dependent and -independent regulatory modes.

    Evidence Mutagenesis, co-immunoprecipitation, and influenza HA apical transport assay in Caco-2 cells

    PMID:10788461

    Open questions at the time
    • Syntaxin-independent mechanism of Munc18-2 action not molecularly defined
    • No in vivo validation in epithelial tissue
  2. 2003 High

    Linking STXBP2 to microtubule-dependent granule translocation in mast cells revealed a pre-fusion role: Munc18-2 associated with secretory granules, interacted selectively with syntaxins 2/3, and was excluded from lipid raft-resident SNARE complexes, placing it upstream of productive SNARE assembly.

    Evidence Overexpression/peptide inhibition, live imaging, nocodazole perturbation, lipid raft fractionation in RBL mast cells

    PMID:12482918 PMID:12935901

    Open questions at the time
    • Direct Munc18-2–tubulin interaction not yet demonstrated
    • Mechanism of raft exclusion of Munc18-2/STX3 unclear
  3. 2005 Medium

    Demonstrating that Slp4-a binds closed-conformation syntaxins 2/3 only in the presence of Munc18-2 established a tripartite regulatory complex linking Rab effectors to SNARE machinery in exocrine secretion.

    Evidence Co-immunoprecipitation with deletion mapping, antibody inhibition of amylase release in permeabilized parotid acinar cells

    PMID:16186111

    Open questions at the time
    • Munc18-2 does not directly bind Slp4-a—structural basis for indirect requirement unknown
    • Relevance beyond parotid cells not tested
  4. 2009 High

    Identification of STXBP2 as the FHL5 disease gene and its requirement for syntaxin 11 stability and cytotoxic lymphocyte degranulation established the first direct genetic link between a Sec1/Munc18 protein and immune deficiency.

    Evidence Patient lymphocyte analysis, co-immunoprecipitation, NK/CTL degranulation assays, ectopic rescue in two independent studies

    PMID:19804848 PMID:19884660

    Open questions at the time
    • Mechanism by which Munc18-2 stabilizes STX11 not resolved at molecular level
    • Whether other syntaxins partially compensate in vivo unclear
  5. 2012 High

    Showing that Munc18-2 is the sole Munc18 isoform forming native complexes with STX11/SNAP-23/VAMP-8 in platelets and that FHL5 platelets have pan-granule secretion failure defined STXBP2 as a non-redundant exocytosis regulator in the megakaryocyte lineage.

    Evidence Co-immunoprecipitation from human platelets, granule secretion assays in FHL5 patient platelets

    PMID:22791290

    Open questions at the time
    • Relative contributions of dense vs. alpha granule defects to bleeding phenotype not dissected
    • Whether Munc18-2 acts at granule-granule fusion in platelets untested
  6. 2013 High

    Structural determination of Munc18-2 at 2.6 Å resolution mapped FHL5 mutations to syntaxin and SNARE binding surfaces, and quantitative binding revealed ~20-fold preference for STX11 over STX3, explaining isoform-selective function in lymphocytes.

    Evidence X-ray crystallography, surface plasmon resonance, mutation mapping, patient cell analysis

    PMID:24194549

    Open questions at the time
    • No co-crystal with STX11 obtained
    • Structural basis for domain 3 loop interactions with SNARE bundle not resolved
  7. 2013 High

    Munc18-2 knockdown selectively impaired secretory granule translocation (not chemokine secretion) in mast cells through a direct, nocodazole-sensitive interaction with tubulin, establishing a mechanistic link between the fusion machinery and microtubule cytoskeleton.

    Evidence siRNA knockdown, co-immunoprecipitation with tubulin, nocodazole perturbation, immunogold EM in mast cells

    PMID:24323579

    Open questions at the time
    • Tubulin binding site on Munc18-2 not mapped
    • Whether tubulin interaction is direct or via adaptors not definitively shown
  8. 2015 High

    Demonstrating that FHL5 mutations R65Q/W arrest late SNARE complex assembly while preserving STX11 binding and stability distinguished a post-chaperoning fusion-promoting function of Munc18-2 and revealed a dominant-negative disease mechanism.

    Evidence In vitro reconstituted membrane fusion, SNARE complex assembly assay, forced expression in primary CTLs/NK cells

    PMID:25564401

    Open questions at the time
    • Exact step of SNARE zippering that is arrested not defined
    • Whether all domain 1 mutations share the same mechanism untested
  9. 2015 High

    Endogenous localization studies in FHL4/FHL5 patient CTLs demonstrated that Munc18-2 chaperones STX11 to the plasma membrane, while its own granule localization is STX11-independent, establishing the directionality of the chaperoning relationship.

    Evidence Immunofluorescence of endogenous proteins in matched FHL4 and FHL5 patient CTLs

    PMID:26771955

    Open questions at the time
    • Transport intermediate carrying STX11 from granules to plasma membrane not identified
    • Whether chaperoning involves co-transport or sequential handoff unknown
  10. 2017 High

    Reconstituted fusion assays showed Munc18-2 drives the transition from STX11-mediated hemifusion to full content mixing, establishing that its role extends beyond SNARE complex assembly to actively catalyzing fusion pore opening.

    Evidence Flipped cell-cell fusion assay measuring lipid vs. content mixing, Munc18-2 wild-type and mutant expression

    PMID:28265073

    Open questions at the time
    • Whether Munc18-2 engages a specific fusion-pore intermediate structurally unknown
    • Lipid composition effects on this transition not explored
  11. 2017 High

    Loss of Munc18-2 in enterocytes disrupted Slp4a/Stx3 interaction and selectively impaired apical trafficking of NHE3 and GLUT5 but not DPPIV, providing a molecular mechanism for FHL5-associated enteropathy.

    Evidence CRISPR/Cas9 knockout in CaCo2 cells, patient biopsies, patient-derived organoids, co-immunoprecipitation

    PMID:28724787

    Open questions at the time
    • Basis for cargo selectivity (NHE3/GLUT5 affected, DPPIV spared) not defined
    • Whether STX3 or another syntaxin mediates unaffected routes unknown
  12. 2018 High

    Conditional knockout of Munc18-2 (but not Munc18-1 or -3) in mast cells and megakaryocytes abolished regulated exocytosis in vivo, confirming non-redundant isoform specificity and demonstrating physiological protection against anaphylaxis and arterial thrombosis.

    Evidence Conditional knockout mice with electrophysiology, EM, secretion assays, anaphylaxis and thrombosis models

    PMID:29599294 PMID:30696774

    Open questions at the time
    • Structural basis for isoform non-redundancy despite conserved architecture not explained
    • Whether compound exocytosis requires Munc18-2 catalytic activity or only scaffolding unknown
  13. 2018 High

    Munc18-2-null intestinal organoids recapitulated microvillus inclusion disease pathology with dynamic microvillus inclusion formation, and rescue with wild-type but not P477L Munc18-2 confirmed variant pathogenicity, establishing an ex vivo disease model.

    Evidence Stxbp2-knockout mouse organoids, lentiviral rescue, confocal/TEM and time-lapse imaging

    PMID:30364784

    Open questions at the time
    • P477L structural effect not characterized
    • Whether organoid phenotype fully recapitulates in vivo intestinal pathology long-term unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the Munc18-2/STX11 co-complex during SNARE zippering, the molecular determinants of cargo selectivity in epithelial trafficking, and whether the Munc18-2–tubulin interaction reflects a direct binding mode with a defined interface.
  • No co-crystal structure of Munc18-2 with STX11 or SNARE complex
  • Tubulin binding interface not mapped
  • Cargo-selective sorting signals downstream of Munc18-2/Stx3 undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0044183 protein folding chaperone 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 7 R-HSA-168256 Immune System 3 R-HSA-9609507 Protein localization 3 R-HSA-109582 Hemostasis 2
Partners
SNAP23STX11STX2STX3SYTL4TUBA1AUNC13DVAMP8
Complex memberships
Munc18-2/STX11 binary complexMunc18-2/STX3 binary complexSTX11/SNAP-23/VAMP-8/Munc18-2 SNARE complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 STXBP2 (Munc18-2) was identified as a binding partner of syntaxin 11 (STX11), and FHL-5 missense mutations in STXBP2 eliminate this interaction, leading to decreased stability of both proteins in patient lymphocytes and markedly reduced NK and CTL degranulation. Co-immunoprecipitation, patient lymphocyte analysis, CD107 degranulation assay American journal of human genetics High 19804848
2009 STXBP2 deficiency impairs cytotoxic granule exocytosis in NK cells, a defect rescued by ectopic expression of wild-type STXBP2; syntaxin 11 expression requires the presence of STXBP2, identifying STXBP2 as required at a late step of the secretory pathway for cytotoxic granule release. Patient lymphoblast analysis, NK cell cytotoxicity assay, ectopic expression rescue experiment The Journal of clinical investigation High 19884660
2000 Munc18-2 forms a complex with syntaxin 3 (a t-SNARE at the apical plasma membrane) and overexpression of wild-type Munc18-2 inhibits apical delivery of influenza hemagglutinin in Caco-2 epithelial cells; point mutants unable to bind syntaxin 3 have differential effects on apical transport, indicating Munc18-2 controls apical membrane trafficking via syntaxin 3 interaction and additional syntaxin-independent mechanisms. Munc18-2 point mutagenesis, co-immunoprecipitation, SNAP-23 displacement assay, influenza HA apical transport assay in Caco-2 cells The Journal of biological chemistry High 10788461
2003 Munc18-2 localizes to secretory granules in mast cells, interacts with syntaxin 2 and syntaxin 3 (not syntaxin 4), redistributes toward lamellipodia upon stimulation and associates with microtubule-aligned granules; overexpression of Munc18-2 or effector-loop-containing peptides inhibits IgE-triggered exocytosis, and disruption of microtubules with nocodazole causes Munc18-2 redistribution and impairs mediator release. Munc18-2 overexpression, peptide inhibition, immunofluorescence/live imaging, nocodazole treatment, mediator release assay Journal of cell science High 12482918
2013 Crystal structure of human Munc18-2 solved at 2.6 Å resolution; surface mutations causing FHL5 (R39P, L130S, E132A, P334L) map to predicted syntaxin and SNARE binding sites; Munc18-2 binds the N-terminal peptide of STX11 with ~20-fold higher affinity than STX3; upon IL-2 activation, increased STX3 levels favor Munc18-2 binding when STX11 is absent, and Munc18-1 expressed in activated CTL can bind STX11. X-ray crystallography, surface plasmon resonance binding assay, mutation mapping, patient cell analysis Proceedings of the National Academy of Sciences of the United States of America High 24194549
2015 STXBP2 R65Q and R65W mutations retain interaction with and stabilization of syntaxin 11 but hinder membrane fusion in vitro by arresting late steps of SNARE-complex assembly; forced expression of these mutants in control CTLs and NK cells diminishes degranulation and cytotoxic activity in a dominant-negative manner. In vitro membrane fusion assay, SNARE complex assembly assay, forced expression in primary CTLs/NK cells, cytotoxicity/degranulation assay Blood High 25564401
2017 Munc18-2 facilitates the transition from lipid-anchored STX11-mediated hemifusion (lipid mixing without content mixing) to complete membrane fusion during CTL lytic granule secretion; wild-type Munc18-2 but not STX11-binding mutants stimulates complete fusion in a reconstituted flipped cell-cell fusion assay, demonstrating Munc18-2 directly promotes SNARE complex assembly beyond its chaperone role. Reconstituted 'flipped' cell-cell fusion assay measuring lipid and content mixing, Munc18-2 mutant expression Proceedings of the National Academy of Sciences of the United States of America High 28265073
2012 Munc18b (STXBP2) is the major Munc18 isoform in platelets and forms complexes with syntaxin 11, SNAP-23, and VAMP-8, as well as Munc13-4 and Rab27; FHL5 patient platelets with biallelic mutations show profoundly defective serotonin, ADP/ATP, platelet factor 4, and lysosomal content secretion, with decreased Munc18b and syntaxin 11 levels. Co-immunoprecipitation from human platelets, platelet secretion assays (serotonin, ADP/ATP release), patient platelet analysis Blood High 22791290
2013 siRNA-mediated silencing of Munc18-2 in mast cells inhibits secretory granule (SG) translocation but not CCL2 chemokine secretion; Munc18-2 (but not STX3) interacts with tubulin in resting cells in a nocodazole-sensitive manner, and this interaction decreases after stimulation, demonstrating Munc18-2 dynamically couples the fusion machinery to the microtubule cytoskeleton. siRNA knockdown, combined knockdown epistasis, immunogold electron microscopy, co-immunoprecipitation with tubulin, nocodazole perturbation, degranulation assay Journal of immunology High 24323579
2017 In FHL5 enterocytes, Munc18-2 is required for Slp4a/Stx3 interaction necessary for fusion of cargo vesicles with the apical plasma membrane; loss of Munc18-2 selectively disrupts trafficking of NHE3 and GLUT5 to the brush border while DPPIV transport is unaffected, causing subapical accumulation of cargo vesicles. CRISPR/Cas9 Munc18-2 knockout in CaCo2 cells, patient biopsy analysis, patient-derived organoid analysis, fluorescence and electron microscopy, co-immunoprecipitation (Slp4a/Stx3) JCI insight High 28724787
2015 Munc18-2 localizes predominantly to cytolytic granules with low levels at the plasma membrane in CTLs; STX11 localizes to the plasma membrane and its plasma membrane localization is lost in FHL5 CTLs lacking Munc18-2, whereas Munc18-2 localization is unaffected in FHL4 CTLs lacking STX11, demonstrating Munc18-2 chaperones STX11 to the plasma membrane. Immunofluorescence localization of endogenous proteins in FHL4 and FHL5 patient CTLs, loss-of-function analysis Traffic High 26771955
2005 Slp4-a (granuphilin-a) interacts with syntaxin 2/3 in a closed conformation only in the presence of Munc18-2, while Munc18-2 itself does not directly bind Slp4-a; the Slp4-a linker domain (residues 144–354) mediates syntaxin 2/3 binding, and antibody interference with this interaction inhibits isoproterenol-stimulated amylase release from permeabilized parotid acinar cells. Co-immunoprecipitation in COS-7 cells, deletion analysis, antibody inhibition in streptolysin-O permeabilized cells, amylase release assay The Journal of biological chemistry Medium 16186111
2003 Munc18-2/syntaxin 3 complexes are spatially excluded from lipid rafts in mast cells, whereas STX3-containing SNARE complexes (with SNAP-23 and VAMP-8) are enriched in rafts, demonstrating that Munc18-2 acts at a step distinct from SNARE complex formation and membrane fusion. Lipid raft fractionation, Western blotting for SNARE and Munc18 proteins in RBL mast cells FEBS letters Medium 12935901
2007 Munc18-2 knockdown in RBL-2H3 mast cells markedly inhibits degranulation without changing syntaxin expression or Ca2+ mobilization; Munc18-2 interacts with syntaxin 3 (not syntaxin 4) both at the plasma membrane and on secretory granules in vivo, suggesting regulation of both granule-granule and granule-plasma membrane fusion. Munc18-2 knockdown, fluorescent chimera co-localization/co-immunoprecipitation, single-cell granule imaging, degranulation assay Molecular immunology Medium 17408745
2013 FHL-5 neutrophils (with STXBP2/Munc18-2 mutations) have a profound defect in granule mobilization resulting in inadequate bacterial killing, particularly of gram-negative E. coli, identifying STXBP2 as required for neutrophil granule exocytosis and bactericidal function. Patient neutrophil functional assays (degranulation, bacterial killing assay), comparison of FHL-5 vs. control neutrophils Blood Medium 23687090
2018 In mast cells, conditional knockout of Munc18-2 (but not Munc18-1 or Munc18-3) causes near-complete absence of regulated exocytosis and abolishes compound (homotypic) exocytosis as shown by plasma membrane capacitance recordings and stereological EM analysis; Munc18-2 cKO mice are protected from anaphylaxis. Conditional knockout mice (Munc18-1, -2, -3 each deleted in mast cells), plasma membrane capacitance recordings, stereological EM, mediator secretion assays, in vivo anaphylaxis model The Journal of biological chemistry High 29599294
2019 Munc18-2 (but not Munc18-1 or Munc18-3) conditional knockout in megakaryocytes ablates release of alpha, dense, and lysosomal granules from platelets; Munc18-2-deficient platelets have defective aggregation at low collagen doses, impaired thrombus formation under shear stress, prolonged bleeding times in vivo, and protection against arterial thrombosis. Conditional knockout mice, platelet granule secretion assays, aggregometry, shear stress thrombus assay, tail bleeding time, arterial thrombosis model The Journal of biological chemistry High 30696774
2011 In pancreatic β-cells, Munc18-2 overexpression increases Ca2+ sensitivity for insulin exocytosis and mediates release of fusion-competent granules at lower cytoplasmic Ca2+ concentrations; Munc18-2 localization is distinct from Munc18-1 and does not redistribute in response to glucose stimulation; the Ca2+ sensitivity of exocytosis depends on phosphorylation status of Munc18 proteins. Overexpression in β-cells, ramp-like caged Ca2+ photorelease, whole-cell patch clamp capacitance recordings, subcellular fractionation/immunofluorescence The Journal of biological chemistry Medium 21690086
2018 Loss of Munc18-2/Stxbp2 in intestinal organoids from knockout mice recapitulates MVID pathology (secretory vesicle accumulation, apical tubulovesicular network, microvillus inclusions); the patient variant P477L fails to rescue the phenotype while wild-type human MUNC18-2 fully restores it; microvillus inclusions form dynamically by intracellular maturation or invagination of apical/basolateral membranes. Munc18-2/Stxbp2-null mouse intestinal organoids, lentiviral rescue with WT vs. P477L variant, confocal and transmission electron microscopy, spinning disc time-lapse microscopy Cellular and molecular gastroenterology and hepatology High 30364784
2013 STXBP2 mutations cause persistent defective membrane trafficking in intestinal epithelial cells and renal tubular cells (intracytoplasmic PAS-positive granule accumulation, enlarged intracytoplasmic CD10-positive apical vesicles, short microvilli), defects that persist after hematopoietic stem cell transplantation, demonstrating STXBP2 function is cell-intrinsic in epithelium. Immunohistochemistry, electron microscopy of patient gut and kidney biopsies Pediatric blood & cancer Medium 23382066
2014 N-terminal syntaxin 11 mutations R4A and L58P (in the Habc domain) abolish binding to Munc18-2, demonstrating that both the N-terminus and Habc domain of STX11 are required for Munc18-2 interaction, with similarity to the dynamic binary binding of neuronal syntaxin 1 to Munc18-1. Ectopic expression, co-immunoprecipitation, functional NK cell degranulation assay in patient cells Frontiers in immunology Medium 24459464
2015 STXBP2 is required in erythroid cells: red blood cells from FHL-5 patients express Munc18-2 and show reduced phosphatidylserine exposure after Ca2+ ionophore treatment; cultured erythroblasts from FHL-5 patients display decreased CD235a expression and aberrant morphology, identifying STXBP2 as required for phospholipid scrambling and normal erythropoiesis. Patient RBC phosphatidylserine exposure assay (Ca2+ ionophore/ionomycin), erythroblast culture with morphological and surface marker analysis Experimental hematology Medium 26320718
2020 STXBP2-R190C mutation does not alter protein expression, subcellular localization, or STXBP2/STX11 interaction, but forced expression in normal CTLs strongly inhibits degranulation and cytolytic activity in a dominant-negative manner, implicating domain 2 of STXBP2 in stabilizing productive interactions required for granule exocytosis. Forced expression in primary CTLs, degranulation assay, cytotoxicity assay, Co-immunoprecipitation, immunofluorescence localization Frontiers in immunology Medium 33162974
2018 STXBP2 and STX11 deficiency is associated with significant reduction in STXBP1 protein and its partner STX1 in patient NK and T cells; functional assays revealed the STXBP1/STX1 axis accounts for up to 50% of NK and CD8+ T-cell cytotoxic activity, suggesting a complementary exocytosis pathway. Patient cell protein expression analysis, NK/CTL degranulation and cytotoxicity assays, IL-2 stimulation rescue Frontiers in immunology Medium 29599780

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood 318 21881043
2009 Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11. American journal of human genetics 310 19804848
2009 Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells. The Journal of clinical investigation 281 19884660
2003 Evidence of a role for Munc18-2 and microtubules in mast cell granule exocytosis. Journal of cell science 105 12482918
2010 Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2. Blood 101 20558610
2010 Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases. Haematologica 100 20823128
2015 Hemophagocytic lymphohistiocytosis caused by dominant-negative mutations in STXBP2 that inhibit SNARE-mediated membrane fusion. Blood 93 25564401
2012 Munc18b/STXBP2 is required for platelet secretion. Blood 72 22791290
2000 Munc18-2, a functional partner of syntaxin 3, controls apical membrane trafficking in epithelial cells. The Journal of biological chemistry 67 10788461
2013 Syntaxin binding mechanism and disease-causing mutations in Munc18-2. Proceedings of the National Academy of Sciences of the United States of America 61 24194549
2013 Persistent defective membrane trafficking in epithelial cells of patients with familial hemophagocytic lymphohistiocytosis type 5 due to STXBP2/MUNC18-2 mutations. Pediatric blood & cancer 56 23382066
2018 MYO5B, STX3, and STXBP2 mutations reveal a common disease mechanism that unifies a subset of congenital diarrheal disorders: A mutation update. Human mutation 51 29266534
2013 Munc18-2 and syntaxin 3 control distinct essential steps in mast cell degranulation. Journal of immunology (Baltimore, Md. : 1950) 49 24323579
2010 STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5. Journal of medical genetics 46 20798128
2017 Disrupted apical exocytosis of cargo vesicles causes enteropathy in FHL5 patients with Munc18-2 mutations. JCI insight 45 28724787
2005 Slp4-a/granuphilin-a interacts with syntaxin-2/3 in a Munc18-2-dependent manner. The Journal of biological chemistry 44 16186111
2013 Defects in neutrophil granule mobilization and bactericidal activity in familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) syndrome caused by STXBP2/Munc18-2 mutations. Blood 41 23687090
2018 Genetic variant spectrum in 265 Chinese patients with hemophagocytic lymphohistiocytosis: Molecular analyses of PRF1, UNC13D, STX11, STXBP2, SH2D1A, and XIAP. Clinical genetics 38 29665027
2003 Munc18-2/syntaxin3 complexes are spatially separated from syntaxin3-containing SNARE complexes. FEBS letters 38 12935901
2007 Munc18-2 regulates exocytotic membrane fusion positively interacting with syntaxin-3 in RBL-2H3 cells. Molecular immunology 34 17408745
2017 SM protein Munc18-2 facilitates transition of Syntaxin 11-mediated lipid mixing to complete fusion for T-lymphocyte cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America 30 28265073
2012 Development of classical Hodgkin's lymphoma in an adult with biallelic STXBP2 mutations. Haematologica 29 23100279
2011 Munc18-1 and Munc18-2 proteins modulate beta-cell Ca2+ sensitivity and kinetics of insulin exocytosis differently. The Journal of biological chemistry 28 21690086
2015 Late-onset severe chronic active EBV in a patient for five years with mutations in STXBP2 (MUNC18-2) and PRF1 (perforin 1). Journal of clinical immunology 27 25947952
2018 Dynamic Formation of Microvillus Inclusions During Enterocyte Differentiation in Munc18-2-Deficient Intestinal Organoids. Cellular and molecular gastroenterology and hepatology 23 30364784
2015 Munc18-2 is required for Syntaxin 11 Localization on the Plasma Membrane in Cytotoxic T-Lymphocytes. Traffic (Copenhagen, Denmark) 22 26771955
2014 An N-Terminal Missense Mutation in STX11 Causative of FHL4 Abrogates Syntaxin-11 Binding to Munc18-2. Frontiers in immunology 19 24459464
2018 Bi-Allelic Mutations in STXBP2 Reveal a Complementary Role for STXBP1 in Cytotoxic Lymphocyte Killing. Frontiers in immunology 18 29599780
2018 Munc18-2, but not Munc18-1 or Munc18-3, controls compound and single-vesicle-regulated exocytosis in mast cells. The Journal of biological chemistry 17 29599294
2022 A Rare STXBP2 Mutation in Severe COVID-19 and Secondary Cytokine Storm Syndrome. Life (Basel, Switzerland) 15 35207437
2020 ELKS1 controls mast cell degranulation by regulating the transcription of Stxbp2 and Syntaxin 4 via Kdm2b stabilization. Science advances 12 32937583
2020 STXBP2-R190C Variant in a Patient With Neonatal Hemophagocytic Lymphohistiocytosis (HLH) and G6PD Deficiency Reveals a Critical Role of STXBP2 Domain 2 on Granule Exocytosis. Frontiers in immunology 11 33162974
2014 Novel Patient with Late-Onset Familial Hemophagocytic Lymphohistiocytosis with STXBP2 Mutations Presenting with Autoimmune Hepatitis, Neurological Manifestations and Infections Associated with Hypogammaglobulinemia. Journal of clinical immunology 11 25491289
2012 Novel mutation in STXBP2 prevents IL-2-induced natural killer cell cytotoxicity. The Journal of allergy and clinical immunology 11 22336081
2017 Identification of STXBP2 as a novel susceptibility locus for myocardial infarction in Japanese individuals by an exome-wide association study. Oncotarget 10 28380445
2021 Spectrum mutations of PRF1, UNC13D, STX11, and STXBP2 genes in Vietnamese patients with hemophagocytic lymphohistiocytosis. International journal of laboratory hematology 8 34339548
2019 Munc18-2, but not Munc18-1 or Munc18-3, regulates platelet exocytosis, hemostasis, and thrombosis. The Journal of biological chemistry 8 30696774
2019 Novel mutations of STXBP2 and LYST associated with adult haemophagocytic lymphohistiocytosis with Epstein-Barr virus infection: a case report. BMC medical genetics 8 30782130
2012 Novel STXBP2 mutation causing familial hemophagocytic lymphohistiocytosis. Indian pediatrics 8 22796692
2000 Gene structure and promoter function of murine Munc18-2, a nonneuronal exocytic Sec1 homolog. Biochemical and biophysical research communications 8 11027553
2022 Monogenic inflammatory bowel disease with STXBP2 mutations is not resolved by hematopoietic stem cell transplantation but can be alleviated via immunosuppressive drug therapy. Clinical immunology (Orlando, Fla.) 7 36503158
2016 Hemophagocytic Lymphohistocytosis in the Chinese Han Population May Be Associated with an STXBP2 Gene Polymorphism. PloS one 6 27513731
2015 Prevalence of type 5 familial hemophagocytic lymphohistiocytosis in Korea and novel mutations in STXBP2. Clinical genetics 6 26451869
2015 Intrinsic defects in erythroid cells from familial hemophagocytic lymphohistiocytosis type 5 patients identify a role for STXBP2/Munc18-2 in erythropoiesis and phospholipid scrambling. Experimental hematology 5 26320718
2019 Familial hemophagocytic lymphohistiocytosis type 5 in a Chinese Tibetan patient caused by a novel compound heterozygous mutation in STXBP2. Medicine 4 31651895
2019 Type 5 Familial Hemophagocytic Lymphohistiocytosis in a Seven-year-old Girl Post Second Bone Marrow Transplantation with Failure to Thrive: STXBP2 Novel Mutation. Cureus 4 31807395
2021 Case Report: Characterizing the Role of the STXBP2-R190C Monoallelic Mutation Found in a Patient With Hemophagocytic Syndrome and Langerhans Cell Histiocytosis. Frontiers in immunology 3 34630398
2021 Germline Compound Heterozygous Variants Identified in the STXBP2 Gene Leading to a Familial Hemophagocytic Lymphohistiocytosis Type 5: A Case Report. Frontiers in pediatrics 2 34249802
2019 Molecular analysis of the novel L243R mutation in STXBP2 reveals impairment of degranulation activity. International journal of hematology 2 31865540
2019 Familial Hemophagocytic Lymphohistiocytosis: A Rare Mutation of STXBP2 in Exon 19. Journal of pediatric genetics 2 31976148
2023 A Case of Fetal Familial Hemophagocytic Lymphohistiocytosis Type 5 caused by STXBP2 Gene Mutation. Clinical laboratory 1 38084697
2022 Secondary Leukemia in a Patient With EBV-HLH Carrying Heterozygous STXBP2 Variant. Journal of pediatric hematology/oncology 1 33661178
2025 Neurological and neuropsychiatric manifestations in a teenager with familial haemophagocytic lymphohistiocytosis with STXBP2 mutation. BMJ case reports 0 40262927