Details for: STX1A

Gene ID: 6804

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: STX1A

Ensembl ID: ENSG00000106089

Description: syntaxin 1A

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • conventional dendritic cell CL0000990
    CSI 13.08
    rCSI 10.92%
    PRS 82.62
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 12.32
    rCSI 14.93%
    PRS 65.78
  • enteroendocrine cell CL0000164
    CSI 9.57
    rCSI 13.07%
    PRS 84.46
  • cerebellar granule cell CL0001031
    CSI 8.46
    rCSI 12.43%
    PRS 79.15
  • innate lymphoid cell CL0001065
    CSI 7.26
    rCSI 14.99%
    PRS 81.03
  • progenitor cell CL0011026
    CSI 6.97
    rCSI 14.82%
    PRS 79.38
  • melanocyte of skin CL1000458
    CSI 6.64
    rCSI 9.04%
    PRS 53.42
  • basal cell of epidermis CL0002187
    CSI 6.33
    rCSI 11.22%
    PRS 54.91
  • regulatory T cell CL0000815
    CSI 5.59
    rCSI 6.48%
    PRS 83.09
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 5.19
    rCSI 11.26%
    PRS 73.69
  • platelet CL0000233
    CSI 4.92
    rCSI 20.39%
    PRS 82.29
  • cerebral cortex neuron CL0010012
    CSI 4.86
    rCSI 19.81%
    PRS 77.49
  • chondrocyte CL0000138
    CSI 4.57
    rCSI 7.26%
    PRS 79.37
  • helper T cell CL0000912
    CSI 4.32
    rCSI 6.11%
    PRS 82.85
  • peripheral nervous system neuron CL2000032
    CSI 4.31
    rCSI 5.87%
    PRS 77.92
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 4.21
    rCSI 5.24%
    PRS 67.38
  • pancreatic D cell CL0000173
    CSI 4.01
    rCSI 3.95%
    PRS 87.37
  • pancreatic A cell CL0000171
    CSI 4.01
    rCSI 4.2%
    PRS 88.17
  • sst GABAergic cortical interneuron CL4023017
    CSI 3.58
    rCSI 4.62%
    PRS 70.64
  • L6b glutamatergic cortical neuron CL4023038
    CSI 3.29
    rCSI 10.28%
    PRS 70.98
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 3.23
    rCSI 10.09%
    PRS 73.17
  • type B pancreatic cell CL0000169
    CSI 3.2
    rCSI 7.08%
    PRS 85.12
  • suprabasal keratinocyte CL4033013
    CSI 3.2
    rCSI 5.22%
    PRS 53.72
  • lung neuroendocrine cell CL1000223
    CSI 3.12
    rCSI 4.61%
    PRS 88.07
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.01
    rCSI 3.6%
    PRS 69.58
  • dopaminergic neuron CL0000700
    CSI 2.99
    rCSI 16.87%
    PRS 72.81
  • cytotoxic T cell CL0000910
    CSI 2.84
    rCSI 16.27%
    PRS 86.79
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.9
    rCSI 11.2%
    PRS 69.99
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.69
    rCSI 4.1%
    PRS 67.3
  • Cajal-Retzius cell CL0000695
    CSI 1.54
    rCSI 12.1%
    PRS 88.28
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.43
    rCSI 2.53%
    PRS 68.96
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.37
    rCSI 5.18%
    PRS 69.85
  • megakaryocyte CL0000556
    CSI 1.25
    rCSI 5.41%
    PRS 88.68
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.16
    rCSI 2.78%
    PRS 73.35
  • pancreatic epsilon cell CL0005019
    CSI 1.11
    rCSI 5.17%
    PRS 90.85
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.1
    rCSI 1.85%
    PRS 69.44
  • pancreatic PP cell CL0002275
    CSI 1.03
    rCSI 4.1%
    PRS 90.55
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.98
    rCSI 3.53%
    PRS 67.46
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 0.72
    rCSI 2.36%
    PRS 72.2
  • type EC enteroendocrine cell CL0000577
    CSI 0.71
    rCSI 2.54%
    PRS 87.77

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [STX1A](/details-gene/6804) (syntaxin 1A) is a protein-coding gene located on chromosome 7q11.23. It encodes a crucial component of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex, which is essential for mediating the fusion of vesicles with the plasma membrane, a process central to exocytosis. Functionally, [STX1A](/details-gene/6804) is indispensable for neurotransmitter release at presynaptic terminals and hormone secretion in endocrine cells. Its expression profile reflects this role, showing high significance in various neuronal populations, such as [cerebellar granule cells](/details-cell/CL0001031) and [cerebral cortex neurons](/details-cell/CL0010012), as well as in secretory cells like [enteroendocrine cells](/details-cell/CL0000164). Interestingly, it also demonstrates high significance in multiple immune cell types, including [conventional dendritic cells](/details-cell/CL0000990) and memory T cells, suggesting a broader role in regulating vesicle-mediated processes in the immune system. Clinically, hemizygous deletion of the [STX1A](/details-gene/6804) gene is associated with Williams syndrome ([186590](https://omim.org/entry/186590)) [Link](https://doi.org/10.1086/514850). ## Cellular Roles and Expression Landscape The **Overall** expression profile of [STX1A](/details-gene/6804) underscores its fundamental role as a core component of the cellular secretion machinery across diverse lineages. Its significance is not restricted to a single system but spans neuronal, immune, and endocrine contexts, highlighting its importance in calcium-regulated exocytosis. The highest significance is observed in [conventional dendritic cells](/details-cell/CL0000990) (CSI: 13.08), followed closely by [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203) (CSI: 12.32), [regulatory T cells](/details-cell/CL0000815), and [helper T cells](/details-cell/CL0000912). This strong association with multiple professional antigen-presenting cells and effector lymphocytes suggests a critical function in immune processes that rely on secretion, such as cytokine release, cytotoxic granule deployment, and potentially the trafficking of peptide-MHC complexes to the cell surface. Consistent with its canonical function, [STX1A](/details-gene/6804) shows high significance in various neuronal populations, including [cerebellar granule cells](/details-cell/CL0001031), [L2/3 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4030059), and [peripheral nervous system neurons](/details-cell/CL2000032). This pattern aligns with its well-established role in mediating the fusion of synaptic vesicles for neurotransmitter release. Furthermore, its high CSI in [enteroendocrine cells](/details-cell/CL0000164) points to a similar role in hormone secretion within the gut. The gene's significance in [platelets](/details-cell/CL0000233), which are known to release factors from granules upon activation, further broadens its functional scope to hemostasis [Link](https://doi.org/10.1182/blood.v100.3.1081). ## Pathways and Molecular Function The functional annotations for [STX1A](/details-gene/6804) confirm its identity as a central player in membrane trafficking. Gene Ontology (GO) terms prominently feature processes related to secretion and vesicle fusion, such as `[Exocytosis](https://www.ebi.ac.uk/QuickGO/term/GO:0006887)`, `[Synaptic vesicle exocytosis](https://www.ebi.ac.uk/QuickGO/term/GO:0016079)`, and `[Calcium-ion regulated exocytosis](https://www.ebi.ac.uk/QuickGO/term/GO:0017156)`. Its molecular function is defined by its `[Snap receptor activity](https://www.ebi.ac.uk/QuickGO/term/GO:0005484)` and `[Snare binding](https://www.ebi.ac.uk/QuickGO/term/GO:0000149)`, localizing it to the `[Snare complex](https://www.ebi.ac.uk/QuickGO/term/GO:0031201)` at the `[Presynaptic active zone membrane](https://www.ebi.ac.uk/QuickGO/term/GO:0048787)`. Reactome pathway analysis provides a systems-level view of its involvement. The gene is a key component of the `[Neurotransmitter release cycle](https://reactome.org/content/detail/R-HSA-112310)`, including specific cycles for acetylcholine, dopamine, GABA, glutamate, and serotonin. This is highly consistent with its expression in diverse neuronal subtypes. Its role in endocrine function is highlighted by its participation in `[Regulation of insulin secretion](https://reactome.org/content/detail/R-HSA-422356)`. The high significance of [STX1A](/details-gene/6804) in immune cells is supported by its inclusion in pathways like `[Cytokine signaling in immune system](https://reactome.org/content/detail/R-HSA-1280215)` and `[Signaling by interleukins](https://reactome.org/content/detail/R-HSA-449147)`, suggesting it facilitates the release of these signaling molecules. The pathway `[Uptake and actions of bacterial toxins](https://reactome.org/content/detail/R-HSA-5339562)`, particularly involving clostridium toxins, further indicates that [STX1A](/details-gene/6804) and the SNARE machinery it forms are direct targets of potent neurotoxins. ## Research Directions The widespread yet cell-type-specific importance of [STX1A](/details-gene/6804) suggests that its regulation and function may be tailored to the specific secretory needs of different cells. While its role in neurons is well-studied, its function in the immune system presents a compelling area for future investigation. ### Proposed Hypotheses: 1. Given its high significance in [conventional dendritic cells](/details-cell/CL0000990), [STX1A](/details-gene/6804) is essential for effective antigen presentation by mediating the final fusion step of MHC class II-loaded vesicles with the plasma membrane, a critical checkpoint for initiating adaptive immune responses. 2. In cytotoxic T lymphocytes (CTLs) and NK cells, [STX1A](/details-gene/6804) is a rate-limiting component of the machinery that directs the polarized secretion of lytic granules (containing perforin and granzymes) towards a target cell, thereby controlling the efficacy of cell-mediated cytotoxicity. 3. Based on its role in sumoylation-regulated endocytosis [Link](https://doi.org/10.1038/srep17669), cell-type-specific post-translational modifications of [STX1A](/details-gene/6804) (e.g., phosphorylation, sumoylation) dictate its interaction partners and fine-tune its activity, allowing it to regulate distinct secretory pathways such as constitutive cytokine release versus rapid degranulation in immune cells. ### Experimental Approach: To test the first hypothesis regarding the role of [STX1A](/details-gene/6804) in antigen presentation, a conditional knockout mouse model could be employed (e.g., *Stx1a*fl/fl crossed with a CD11c-Cre driver to achieve deletion specifically in dendritic cells). Bone marrow-derived dendritic cells (BMDCs) from these knockout mice and wild-type controls could be pulsed with a model antigen (e.g., ovalbumin). The ability of these BMDCs to activate antigen-specific OT-II T cells would be quantified through co-culture assays measuring T cell proliferation (e.g., via CFSE dilution) and cytokine secretion (e.g., IL-2 via ELISA). Additionally, total internal reflection fluorescence (TIRF) microscopy could be used to directly visualize and quantify the docking and fusion of fluorescently-tagged MHC-II vesicles at the plasma membrane in live BMDCs, providing direct evidence for the role of [STX1A](/details-gene/6804) in this specific membrane fusion event. ### Therapeutic Potential: As a core component of the exocytosis machinery, systemic targeting of [STX1A](/details-gene/6804) would likely lead to severe, widespread toxicity. However, its role as a target for botulinum neurotoxins demonstrates that inhibiting its function can have potent therapeutic effects in specific contexts (e.g., neuromuscular junctions). This principle could be extended to other pathologies. For diseases characterized by excessive secretion, such as certain forms of epilepsy (hyperexcitability) or endocrine tumors (hormone overproduction), developing cell-type-specific inhibitors of [STX1A](/details-gene/6804) or its associated SNARE complex could be a viable strategy. Given its high expression in specific immune cell subsets, modulating [STX1A](/details-gene/6804) function could also offer a novel approach to tuning immune responses, for instance, by dampening cytokine storms or enhancing cytotoxic cell activity. The primary therapeutic strategy would likely involve inhibition rather than activation.

Genular Protein ID: 1577028649

Symbol: STX1A_HUMAN

Name: Syntaxin-1A

UniProtKB Accession Codes:

Q16623 O15447 O15448 Q12936 Q75MD9 Q7Z5K3 Q9BPZ6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CORUM 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 21 Ensembl 2 ExpressionAtlas 1 GO 35 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 Reactome 14 RefSeq 2 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 2 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7622072

Title: Cloning and sequence analysis of a cDNA encoding human syntaxin 1A, a polypeptide essential for exocytosis.

PubMed ID: 7622072

DOI: 10.1016/0378-1119(95)00152-v

PubMed ID: 9311751

Title: Hemizygous deletion of the syntaxin 1A gene in individuals with Williams syndrome.

PubMed ID: 9311751

DOI: 10.1086/514850

PubMed ID: 11977160

Title: Refinement of the genomic structure of STX1A and mutation analysis in nondeletion Williams syndrome patients.

PubMed ID: 11977160

DOI: 10.1002/ajmg.10321

PubMed ID: 9003414

Title: Novel isoform of syntaxin 1 is expressed in mammalian cells.

PubMed ID: 9003414

DOI: 10.1042/bj3210151

PubMed ID: 9177791

Title: Mapping of the human HPC-1/syntaxin 1A gene (STX1A) to chromosome 7 band q11.2.

PubMed ID: 9177791

DOI: 10.1006/geno.1997.4650

PubMed ID: 12586365

Title: Expression of syntaxin 1C, an alternative splice variant of HPC-1/syntaxin 1A, is enhanced by phorbol-ester stimulation in astroglioma: participation of the PKC signaling pathway.

PubMed ID: 12586365

DOI: 10.1016/s0014-5793(03)00015-2

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10644452

Title: Expression analysis of the human HPC-1/syntaxin 1A, a gene deleted in Williams syndrome.

PubMed ID: 10644452

DOI: 10.1006/geno.1999.5987

PubMed ID: 12130530

Title: Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion.

PubMed ID: 12130530

DOI: 10.1182/blood.v100.3.1081

PubMed ID: 12730201

Title: Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Munc18.

PubMed ID: 12730201

DOI: 10.1074/jbc.m300492200

PubMed ID: 15459722

Title: Syntabulin is a microtubule-associated protein implicated in syntaxin transport in neurons.

PubMed ID: 15459722

DOI: 10.1038/ncb1169

PubMed ID: 15822905

Title: Phosphoproteomic analysis of synaptosomes from human cerebral cortex.

PubMed ID: 15822905

DOI: 10.1021/pr0498436

PubMed ID: 23091057

Title: Munc18-1 controls SNARE protein complex assembly during human sperm acrosomal exocytosis.

PubMed ID: 23091057

DOI: 10.1074/jbc.m112.409649

PubMed ID: 26635000

Title: SUMOylation of Syntaxin1A regulates presynaptic endocytosis.

PubMed ID: 26635000

DOI: 10.1038/srep17669

Sequence Information:

  • Length: 288
  • Mass: 33023
  • Checksum: 8AC787EFCE65ACA1
  • Sequence:
    • MKDRTQELRT AKDSDDDDDV AVTVDRDRFM DEFFEQVEEI RGFIDKIAEN VEEVKRKHSA 
ILASPNPDEK TKEELEELMS DIKKTANKVR SKLKSIEQSI EQEEGLNRSS ADLRIRKTQH 
STLSRKFVEV MSEYNATQSD YRERCKGRIQ RQLEITGRTT TSEELEDMLE SGNPAIFASG 
IIMDSSISKQ ALSEIETRHS EIIKLENSIR ELHDMFMDMA MLVESQGEMI DRIEYNVEHA 
VDYVERAVSD TKKAVKYQSK ARRKKIMIII CCVILGIVIA STVGGIFA