Affinage

STXBP2

Syntaxin-binding protein 2 · UniProt Q15833

Length
593 aa
Mass
66.5 kDa
Annotated
2026-06-10
53 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STXBP2 (Munc18-2) is a SEC1/Munc18-family protein that serves as both a syntaxin chaperone and a direct, active component of the core SNARE-mediated membrane fusion machinery driving regulated exocytosis across multiple secretory cell types (PMID:19804848, PMID:25564401, PMID:28265073). In cytotoxic lymphocytes it binds the N-terminal peptide of syntaxin 11 (STX11) with ~20-fold higher affinity than syntaxin 3, stabilizes STX11, and chaperones it to the plasma membrane for lytic granule fusion; loss of STXBP2 destabilizes STX11 and abolishes NK and CTL degranulation, the basis of familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) (PMID:19804848, PMID:19884660, PMID:24194549, PMID:26771955, PMID:24459464). Beyond chaperoning, STXBP2 catalyzes the late fusion step itself: in reconstituted assays, STX11-cognate SNAREs alone support only hemifusion, while wild-type STXBP2 — but not STX11-binding-impaired mutants — drives the transition from hemifusion to complete content mixing by promoting SNARE-complex assembly, and dominant-negative disease mutations that retain STX11 binding arrest assembly at this late step (PMID:25564401, PMID:28265073). This fusion-promoting role extends to mast cell, platelet, and neutrophil granule exocytosis, where STXBP2 acts within complexes containing STX11, SNAP-23, and VAMP-8 and is required for compound (granule-granule) fusion and secretion from all granule classes (PMID:22791290, PMID:29599294, PMID:30696774, PMID:23687090). In epithelial cells STXBP2 partners with syntaxin 2/3 and, via Slp4a, mediates apical vesicle fusion; its loss causes cargo-selective mislocalization of brush-border proteins and recapitulates microvillus inclusion disease (PMID:10788461, PMID:16186111, PMID:28724787, PMID:30364784). In mast cells STXBP2 additionally couples secretory granule translocation to the microtubule cytoskeleton through a nocodazole-sensitive tubulin interaction (PMID:12482918, PMID:24323579).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 High

    Established that Munc18-2 engages an apical-membrane t-SNARE and functionally gates polarized membrane traffic, defining its core role as a syntaxin-binding regulator of fusion.

    Evidence In vitro and in vivo binding assays plus hemagglutinin apical transport assay in Caco-2 cells with mutagenesis

    PMID:10788461

    Open questions at the time
    • Did not resolve whether Munc18-2 promotes or inhibits fusion at the molecular step
    • Restricted to syntaxin 3; STX11 partnership not yet known
  2. 2003 Medium

    Showed Munc18-2 operates in mast cell granule exocytosis and physically couples the fusion machinery to microtubules, linking granule transport to fusion control.

    Evidence Subcellular localization, dominant-negative peptide inhibition, nocodazole disruption, and tubulin co-IP in mast cells

    PMID:12482918 PMID:12935901

    Open questions at the time
    • Spatial separation of Munc18-2/STX3 from SNARE complexes left its exact mechanistic step ambiguous
    • Single-lab localization data
  3. 2005 Medium

    Defined an indirect link between Munc18-2 and the granule-tethering protein Slp4a, where Munc18-2 stabilizes the closed syntaxin conformation that Slp4a recognizes.

    Evidence Co-IP with deletion mapping in COS-7 cells, endogenous complex detection, and antibody inhibition in permeabilized acinar cells

    PMID:16186111

    Open questions at the time
    • Munc18-2 does not bind Slp4a directly; coupling is via syntaxin conformation
    • Tested in exocrine/heterologous systems only
  4. 2009 High

    Identified STX11 as the principal lymphocyte partner of STXBP2 and showed FHL-5 mutations abolish this interaction, destabilize both proteins, and ablate cytotoxic degranulation — establishing the disease mechanism.

    Evidence Co-IP, patient lymphocyte stability analysis, CD107 degranulation assay, and ectopic WT rescue in two concurrent studies

    PMID:19804848 PMID:19884660

    Open questions at the time
    • Did not distinguish chaperone stabilization from a direct fusion role
    • Step in the secretory pathway not pinpointed
  5. 2013 High

    Provided the structural framework: a crystal structure mapped disease mutations to syntaxin/SNARE binding surfaces and quantified the high-affinity STX11 N-peptide interaction relative to STX3.

    Evidence X-ray crystallography at 2.6 Å, surface plasmon resonance, mutation mapping, and Western blot of IL-2-activated CTL

    PMID:24194549

    Open questions at the time
    • Static structure did not capture the fusion-promoting conformational cycle
    • Functional consequence of each mapped mutation not all tested
  6. 2013 Medium

    Extended STXBP2 function to platelet and neutrophil granule exocytosis, defining a STX11/SNAP-23/VAMP-8 effector complex and demonstrating granule-mobilization defects underlie patient immunodeficiency.

    Evidence Co-IP and granule secretion assays in patient platelets; neutrophil granule mobilization and bacterial killing assays

    PMID:22791290 PMID:23687090

    Open questions at the time
    • Patient-derived correlative data, not clean genetic ablation
    • Stoichiometry and assembly order of the complex unresolved
  7. 2014 Medium

    Defined the bipartite STX11 binding requirement (N-terminus plus Habc domain) and reinforced the chaperone-stabilization model.

    Evidence Co-IP of STX11 point mutants in an ectopic system with patient lymphocyte expression analysis

    PMID:24459464

    Open questions at the time
    • Ectopic overexpression context
    • Did not test fusion consequence of altered binding mode
  8. 2015 High

    Demonstrated directly that STXBP2 is an active fusion catalyst, not merely a chaperone: in vitro fusion assays showed dominant-negative R65 mutants retain STX11 binding yet arrest SNARE assembly at a late step.

    Evidence In vitro SNARE-mediated membrane fusion reconstitution, Co-IP, and forced expression with degranulation/cytotoxicity assays

    PMID:25564401 PMID:26771955

    Open questions at the time
    • Precise conformational transition driving SNARE zippering not visualized
    • How dominant-negative mutants poison wild-type complexes mechanistically unclear
  9. 2017 High

    Resolved the exact fusion step: STXBP2 drives the transition from hemifusion to complete content mixing, establishing it as a core component of the fusion machinery; in epithelia it enables Slp4a/STX3-dependent cargo-selective apical fusion.

    Evidence Reconstituted flipped cell-cell fusion assay with lipid- vs content-mixing readouts and binding-impaired mutants; CRISPR KO in CaCo2 cells with cargo trafficking assays and patient material

    PMID:28265073 PMID:28724787

    Open questions at the time
    • Why specific cargoes (NHE3, GLUT5) but not DPPIV depend on STXBP2 is unexplained
    • Coupling between fusion catalysis and cargo selectivity unresolved
  10. 2018 Medium

    Genetic ablation studies established STXBP2 as non-redundant with Munc18-1/-3 for compound granule exocytosis and recapitulated microvillus inclusion disease, with rescue confirming gene-specific causality.

    Evidence Conditional KO mice with patch-clamp capacitance, stereological EM, in vivo anaphylaxis; Stxbp2-null intestinal organoids with WT vs patient-variant rescue and live imaging

    PMID:29599294 PMID:30364784

    Open questions at the time
    • Molecular basis of homotypic (granule-granule) fusion requirement not dissected
    • Link between fusion defect and microvillus inclusion morphogenesis mechanistic but incomplete
  11. 2019 High

    Confirmed in vivo that STXBP2 is essential for platelet granule release across all three granule types and for hemostasis and thrombosis.

    Evidence Platelet-specific conditional KO mice with secretion assays, aggregometry, shear thrombus formation, bleeding-time and thrombosis models, and EM

    PMID:30696774

    Open questions at the time
    • Did not address how STXBP2 coordinates the distinct granule classes mechanistically
  12. 2020 Medium

    Refined understanding of dominant-negative pathology by showing the R190C mutation impairs degranulation without altering expression, localization, or STX11 binding, pointing to a downstream functional defect.

    Evidence Co-IP, immunofluorescence, and forced expression in primary CTLs with degranulation/cytotoxicity assays

    PMID:33162974

    Open questions at the time
    • The downstream interaction or non-productive complex disrupted by R190C is not identified
    • Single-lab functional inference

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how STXBP2 mechanistically achieves cargo and granule-class selectivity and how its phosphorylation tunes Ca2+ sensitivity of fusion across cell types.
  • No structure of STXBP2 engaged with an assembled SNARE complex during fusion
  • Regulatory inputs (phosphorylation, Rab27/Munc13-4) controlling STXBP2 activity not mechanistically defined
  • Erythrocyte and STXBP1-axis roles rest on low-confidence single-patient data

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 3 GO:0060090 molecular adaptor activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3 GO:0005856 cytoskeleton 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-109582 Hemostasis 2
Partners
MUNC13-4SLP4ASNAP-23STX11STX2STX3TUBULINVAMP-8
Complex memberships
Munc18-2/syntaxin-3 complexSTXBP2-STX11-SNAP-23-VAMP-8 SNARE complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 STXBP2 (Munc18-2) interacts with syntaxin 11 (a SNARE protein mutated in FHL-4); missense mutations in STXBP2 found in FHL-5 patients eliminate this interaction, leading to decreased stability of both proteins in patient lymphocytes, and markedly reduced NK and CTL degranulation as measured by CD107 degranulation assay. Co-immunoprecipitation, patient lymphocyte protein stability analysis, CD107 degranulation assay American journal of human genetics High 19804848
2009 STXBP2 (Munc18-2) is required at a late step of the secretory pathway for cytotoxic granule exocytosis in NK cells; syntaxin-11 is the main binding partner of STXBP2 in lymphocytes, and its expression requires the presence of STXBP2. Ectopic expression of wild-type STXBP2 rescued the impaired granule exocytosis in patient-derived NK cells. Loss-of-function (patient lymphoblasts with decreased STXBP2), ectopic expression rescue, Co-immunoprecipitation The Journal of clinical investigation High 19884660
2000 Munc18-2 forms a complex with syntaxin 3, a t-SNARE localized to the apical plasma membrane in epithelial cells. Munc18-2 point mutants with reduced syntaxin-3 binding also displaced SNAP-23 from syntaxin-3 complexes when overexpressed in Caco-2 cells. Overexpression of wild-type Munc18-2 inhibited apical delivery of influenza virus hemagglutinin, demonstrating a functional role in apical membrane trafficking. In vitro binding assay, in vivo co-immunoprecipitation in Caco-2 cells, hemagglutinin apical transport assay, site-directed mutagenesis The Journal of biological chemistry High 10788461
2003 In mast cells, Munc18-2 localizes to secretory granules (while Munc18-3 localizes to the plasma membrane) and interacts with syntaxin 2 or 3. Overexpression of Munc18-2 or interfering effector-loop peptides inhibited IgE-triggered exocytosis. Upon stimulation, Munc18-2 redistributes into lamellipodia and associates with microtubule-aligned granules; disruption of microtubules with nocodazole redistributes Munc18-2 and impairs mediator release, indicating Munc18-2 couples secretory granule dynamics to the microtubule network. Subcellular fractionation/immunolocalization, overexpression and dominant-negative peptide inhibition, nocodazole microtubule disruption, mediator release assay Journal of cell science Medium 12482918
2013 Crystal structure of human Munc18-2 solved at 2.6 Å resolution. Eighteen disease-causing point mutations were mapped; four surface mutations (R39P, L130S, E132A, P334L) map exclusively 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 can compensate for absent STX11, and Munc18-1 (expressed in IL-2-activated CTL) is also capable of binding STX11, explaining partial functional rescue. X-ray crystallography (2.6 Å), surface plasmon resonance binding assay, patient mutation mapping, Western blot of IL-2-activated CTL Proceedings of the National Academy of Sciences of the United States of America High 24194549
2015 STXBP2 mutations R65Q and R65W retain the ability to interact with and stabilize syntaxin 11, but act in a dominant-negative fashion to inhibit NK cell degranulation and cytotoxic activity. Mechanistic in vitro membrane fusion assays show these mutations arrest SNARE-complex assembly at a late step, directly implicating STXBP2 in promoting SNARE-complex assembly during lytic granule fusion. In vitro SNARE-mediated membrane fusion assay, Co-immunoprecipitation, forced expression in CTL/NK cells, degranulation and cytotoxicity assays Blood High 25564401
2012 Munc18b (STXBP2) is required for platelet secretion from all three granule types (alpha, dense, lysosomal). In platelets, Munc18b forms complexes with syntaxin-11, SNAP-23, and VAMP-8; FHL5 patients with biallelic STXBP2 mutations show decreased Munc18b and markedly reduced syntaxin-11 levels, while other syntaxins are unaffected. Munc13-4 and Rab27 were also found associated with this complex. Co-immunoprecipitation in human platelets, granule secretion assays (serotonin, ADP/ATP, platelet factor 4, lysosomal release) in FHL5 patient platelets Blood Medium 22791290
2013 In mast cells, siRNA-mediated silencing of Munc18-2 inhibits secretory granule translocation (but not CCL2 chemokine secretion), while silencing of syntaxin 3 inhibits membrane fusion; combined knockdown produces additive inhibitory effect. Munc18-2 and STX3 are both located on the granule surface and at cytoskeletal clusters. In resting cells, Munc18-2 (but not STX3) interacts with tubulin, an interaction sensitive to nocodazole and decreased after stimulation, demonstrating Munc18-2 dynamically couples fusion machinery to microtubules. siRNA knockdown, immunogold electron microscopy, co-immunoprecipitation with tubulin, nocodazole treatment, degranulation assay Journal of immunology (Baltimore, Md. : 1950) Medium 24323579
2005 Slp4-a/granuphilin-a interacts with a closed conformation of syntaxin-2/3 in a Munc18-2-dependent manner; Munc18-2 itself does not directly interact with Slp4-a. The syntaxin-2/3 binding site on Slp4-a maps to a linker domain (residues 144-354). The Slp4-a·syntaxin-2 complex is present in rat parotid glands, and antibody against the Slp4-a linker domain inhibits isoproterenol-stimulated amylase release from permeabilized acinar cells. Co-immunoprecipitation in COS-7 cells, deletion analysis, endogenous complex detection in parotid gland, antibody inhibition in permeabilized acinar cells The Journal of biological chemistry Medium 16186111
2003 In mast cell lipid rafts, Munc18-2/syntaxin-3 complexes are spatially separated from syntaxin-3-containing SNARE complexes (syntaxin-3/SNAP-23/VAMP-8), with SNARE complexes enriched in rafts while Munc18-2/syntaxin-3 complexes are excluded. This spatial separation suggests Munc18-2 acts at a step different from SNARE complex formation and fusion. Lipid raft fractionation, co-immunoprecipitation FEBS letters Medium 12935901
2007 Munc18-2 knockdown in RBL-2H3 mast cells markedly inhibits degranulation without changing syntaxin expression levels or Ca2+ mobilization. Using chimeric fluorescent fusion proteins, Munc18-2 interaction with syntaxin-3 (but not syntaxin-4) was demonstrated in vivo both on the plasma membrane and on secretory granules, suggesting roles in both granule-granule and granule-plasma membrane fusion. siRNA knockdown, fluorescent chimera co-localization, degranulation assay, live cell imaging Molecular immunology Medium 17408745
2017 In a reconstituted cell-cell fusion assay, lipid-anchored STX11 and its cognate SNARE proteins support lipid exchange (hemifusion) but not complete cytoplasmic content mixing. Addition of wild-type Munc18-2, but not of Munc18-2 mutants with impaired STX11 binding, drives transition from hemifusion to complete membrane fusion, establishing that Munc18-2 is a direct component of the core fusion machinery that promotes SNARE complex assembly to achieve full membrane merging. Reconstituted flipped cell-cell fusion assay, mutant Munc18-2 constructs, content-mixing vs. lipid-mixing readouts Proceedings of the National Academy of Sciences of the United States of America High 28265073
2017 In intestinal enterocytes, Munc18-2 is required for Slp4a/Stx3 interaction and fusion of cargo vesicles with the apical plasma membrane. Loss of Munc18-2 (via CRISPR/Cas9 KO in CaCo2 cells) selectively disrupts trafficking of specific apical brush-border proteins (NHE3 and GLUT5) while leaving DPPIV transport unaffected, causing subapical accumulation of cargo vesicles. CRISPR/Cas9 knockout in CaCo2 cells, Co-immunoprecipitation (Slp4a/Stx3 interaction), fluorescence and electron microscopy of patient biopsies and organoids, cargo trafficking assays JCI insight High 28724787
2015 Munc18-2 localizes predominantly to cytolytic granules in CTL with low levels at the plasma membrane where STX11 resides. In FHL5 CTL lacking Munc18-2, STX11 is lost from the plasma membrane, while Munc18-2 localization is unaffected by absence of STX11 in FHL4 CTL, demonstrating Munc18-2 is required to chaperone STX11 to the plasma membrane for final granule fusion. Immunofluorescence localization in patient-derived CTL (FHL4 and FHL5), subcellular fractionation Traffic (Copenhagen, Denmark) Medium 26771955
2018 Conditional knockout of Munc18-2 (but not Munc18-1 or Munc18-3) in mast cells almost completely abolishes exocytosis as measured by plasma membrane capacitance recordings, and eliminates homotypic granule fusion (compound exocytosis) by stereological EM analysis. Munc18-2 cKO mice are significantly protected from anaphylaxis. Conditional knockout mice, whole-cell patch clamp capacitance recordings, stereological EM analysis, mediator secretion assays, in vivo anaphylaxis model The Journal of biological chemistry High 29599294
2019 Conditional knockout of Munc18-2 (but not Munc18-1 or Munc18-3) in platelets ablates release from alpha, dense, and lysosomal granules. Munc18-2-deficient platelets show defective aggregation at low collagen doses, impaired thrombus formation under shear stress, prolonged arterial and venous bleeding times in vivo, and protection against arterial thrombosis. Conditional knockout mice, granule secretion assays, platelet aggregometry, in vitro thrombus formation under shear, in vivo bleeding time and arterial thrombosis models, design-based stereological EM The Journal of biological chemistry High 30696774
2013 FHL-5 neutrophils carrying STXBP2/Munc18-2 mutations show a profound defect in granule mobilization, resulting in inadequate bacterial killing of gram-negative E. coli but not S. aureus (which depends on NADPH oxidase activity instead), demonstrating a role for STXBP2 in neutrophil granule exocytosis. Patient-derived neutrophil granule mobilization assays, bacterial killing assays with E. coli and S. aureus Blood Medium 23687090
2011 In pancreatic beta-cells, both Munc18-1 and Munc18-2 augment glucose-stimulated insulin secretion, but they have distinct subcellular localizations; only Munc18-1 redistributes upon glucose stimulation. Munc18-2 overexpression shifts Ca2+ sensitivity of insulin exocytosis, mediating release of fusion-competent granules at lower cytoplasmic Ca2+ concentrations. The Ca2+ sensitivity of exocytosis depends on the phosphorylation status of Munc18 proteins. Overexpression in beta-cells, whole-cell patch clamp with caged Ca2+ photorelease, subcellular localization by immunofluorescence, glucose-stimulated secretion assay The Journal of biological chemistry Medium 21690086
2018 Loss of Munc18-2/Stxbp2 in mouse intestinal organoids recapitulates MVID pathological features (apical vesicle accumulation, tubulovesicular network, microvillus inclusions). The phenotype is fully rescued by transgenic wild-type human MUNC18-2 but not by the patient variant P477L. Time-lapse microscopy revealed microvillus inclusions form dynamically by intracellular maturation or invagination of apical or basolateral plasma membrane. Munc18-2/Stxbp2-null mouse intestinal organoids, lentiviral rescue with WT vs. patient mutant, confocal and transmission electron microscopy, spinning disc time-lapse microscopy Cellular and molecular gastroenterology and hepatology Medium 30364784
2014 Both the N-terminus and Habc domain of syntaxin-11 are required for binding to Munc18-2: STX11 mutations R4A and L58P (located in N-terminal and Habc domain respectively) abolish Munc18-2 binding in an ectopic expression system, even though L58P is expressed at levels comparable to wild-type. In patient cells, the L58P mutation decreases syntaxin-11 expression, consistent with Munc18-2 stabilizing STX11. Co-immunoprecipitation in ectopic expression system, patient lymphocyte protein expression analysis Frontiers in immunology Medium 24459464
2015 Erythrocytes express Munc18-2, and FHL-5 patient red blood cells expose less phosphatidylserine on their surface upon Ca2+ ionophore treatment (ionomycin), indicating STXBP2 is required for phospholipid scrambling in erythrocytes. Patient-derived erythroblasts also display defective erythropoiesis with decreased CD235a expression and aberrant cell morphology. Patient-derived erythrocyte phosphatidylserine exposure assay (annexin V), cultured erythroblast differentiation assay with CD235a flow cytometry Experimental hematology Low 26320718
2020 The STXBP2-R190C mutation does not alter STXBP2 expression, subcellular localization, or the STXBP2/STX11 interaction, but forced expression of this mutant into normal CTLs strongly inhibits degranulation and cytolytic activity in a dominant-negative manner, suggesting R190C stabilizes non-productive STXBP2/STX11 complexes or impairs downstream interactions with other factors. Co-immunoprecipitation, immunofluorescence localization, forced expression in primary CTLs, degranulation and cytotoxicity assays Frontiers in immunology Medium 33162974
2018 STXBP2 deficiency leads to a concomitant reduction in STXBP1 and its partner STX1 expression. Functional analysis demonstrates that the STXBP1/STX1 axis contributes to as much as 50% of NK and CD8+ T-cell cytotoxic activity, revealing an interplay between STXBP2 and STXBP1 pathways in regulating granule exocytosis. Patient-derived cells with hypomorphic STXBP2 mutations, Western blot for STXBP1/STX1, NK and T-cell cytotoxicity/degranulation assays Frontiers in immunology Low 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 321 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 Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases. Haematologica 102 20823128
2010 Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2. Blood 101 20558610
2015 Hemophagocytic lymphohistiocytosis caused by dominant-negative mutations in STXBP2 that inhibit SNARE-mediated membrane fusion. Blood 94 25564401
2012 Munc18b/STXBP2 is required for platelet secretion. Blood 73 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 39 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
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 28 25947952
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
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 20 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 12 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 9 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
2015 Prevalence of type 5 familial hemophagocytic lymphohistiocytosis in Korea and novel mutations in STXBP2. Clinical genetics 7 26451869
2016 Hemophagocytic Lymphohistocytosis in the Chinese Han Population May Be Associated with an STXBP2 Gene Polymorphism. PloS one 6 27513731
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
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 4 34630398
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
2019 Molecular analysis of the novel L243R mutation in STXBP2 reveals impairment of degranulation activity. International journal of hematology 3 31865540
2022 Secondary Leukemia in a Patient With EBV-HLH Carrying Heterozygous STXBP2 Variant. Journal of pediatric hematology/oncology 2 33661178
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 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
2025 Neurological and neuropsychiatric manifestations in a teenager with familial haemophagocytic lymphohistiocytosis with STXBP2 mutation. BMJ case reports 0 40262927

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