STX1A Gene

HGNC Family	Syntaxins (STX)
Name	syntaxin 1A (brain)
Description	This gene encodes a member of the syntaxin superfamily. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins possess a single C-terminal transmembrane domain, a SNARE [Soluble NSF (N-ethylmaleimide-sensitive fusion protein)-Attachment protein REceptor] domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels via the C-terminal H3 domain. This gene product is a key molecule in ion channel regulation and synaptic exocytosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSyntaxin 1A (STX1A) is a core component of the neuronal exocytic SNARE complex that mediates membrane fusion and neurotransmitter release. In neurons and neuroendocrine cells, STX1A partners with SNAP‐25 and synaptobrevin to drive fast and regulated vesicle fusion events. Its activity is tightly controlled by interactions with the Sec1/Munc18–1 protein, which binds STX1A via distinct mechanistic modes—an arrangement that is critical for both vesicle docking and the transition to an active, fusion–competent state."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, STX1A also forms part of specialized signaling complexes such as with Ca(v)3.2 T–type calcium channels, where the interaction helps modulate channel availability and supports low–threshold exocytosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in synaptic vesicle fusion, STX1A interacts with key membrane transporters to modulate their trafficking and function. For example, its association with the dopamine transporter (DAT) influences DAT dimerization and phosphorylation, thereby contributing to the fine–tuning of dopaminergic neurotransmission."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, STX1A regulates norepinephrine transporter (NET) dynamics upon amphetamine exposure by forming complexes that affect transporter surface expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSTX1A is also essential in specialized secretory cells. In auditory hair cells, for instance, its Ca²⁺–dependent binding to otoferlin is central to coupling calcium signals with synaptic vesicle release, an interaction whose disruption is linked to deafness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Structural studies using solution NMR have revealed that, in its membrane–bound “prefusion” state, STX1A adopts a partially zippered conformation that may facilitate the sequential assembly of the SNARE complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, lateral clustering of STX1A in the plasma membrane—regulated by interactions with acidic phospholipids such as phosphatidylinositol 4,5–bisphosphate—helps define exocytotic sites, while specific domains (including the N–peptide) are vital for its regulated interaction with Munc18a during the closed‐to–open transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its fundamental role in membrane fusion, STX1A is implicated in modulating neuronal excitability and in the pathogenesis of neuropsychiatric disorders. Alterations in STX1A expression have been associated with autism spectrum conditions; studies have reported both increased expression in certain high–functioning autistic individuals and decreased mRNA levels in distinct brain regions, suggesting that dysregulation of STX1A may affect serotonergic neurotransmission."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Similarly, mutations in ion channel subunits that impair regulation by STX1A contribute to epileptic phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, cleavage of STX1A by neurotoxins such as botulinum neurotoxins disrupts its normal function in SNARE complex formation, leading not only to impaired exocytosis but also to neuronal degeneration, while reductions in syntaxin family proteins have been correlated with synaptic deficits observed in conditions like dementia with Lewy bodies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Colin Rickman, Claire N Medine, Axel Bergmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functionally and spatially distinct modes of munc18-syntaxin 1 interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M700227200"}], "href": "https://doi.org/10.1074/jbc.M700227200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17264080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17264080"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Norbert Weiss, Shahid Hameed, José M Fernández-Fernández, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Ca(v)3.2/syntaxin-1A signaling complex controls T-type channel activity and low-threshold exocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.290882"}], "href": "https://doi.org/10.1074/jbc.M111.290882"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22130660"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22130660"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ki-Hwan Lee, Mi-Young Kim, Dong-Hwan Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syntaxin 1A and receptor for activated C kinase interact with the N-terminal region of human dopamine transporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/b:nere.0000026404.08779.43"}], "href": "https://doi.org/10.1023/b:nere.0000026404.08779.43"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15202772"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15202772"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Concetta Dipace, Uhna Sung, Francesca Binda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Amphetamine induces a calcium/calmodulin-dependent protein kinase II-dependent reduction in norepinephrine transporter surface expression linked to changes in syntaxin 1A/transporter complexes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.106.026690"}], "href": "https://doi.org/10.1124/mol.106.026690"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17032905"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17032905"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Neeliyath A Ramakrishnan, Marian J Drescher, Dennis G Drescher "}, {"type": "b", "children": [{"type": "t", "text": "Direct interaction of otoferlin with syntaxin 1A, SNAP-25, and the L-type voltage-gated calcium channel Cav1.3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M803605200"}], "href": "https://doi.org/10.1074/jbc.M803605200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19004828"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19004828"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Binyong Liang, Volker Kiessling, Lukas K Tamm "}, {"type": "b", "children": [{"type": "t", "text": "Prefusion structure of syntaxin-1A suggests pathway for folding into neuronal trans-SNARE complex fusion intermediate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1314699110"}], "href": "https://doi.org/10.1073/pnas.1314699110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24218570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24218570"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "David H Murray, Lukas K Tamm "}, {"type": "b", "children": [{"type": "t", "text": "Molecular mechanism of cholesterol- and polyphosphoinositide-mediated syntaxin clustering."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi201307u"}], "href": "https://doi.org/10.1021/bi201307u"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21916482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21916482"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Karen N Colbert, Douglas A Hattendorf, Thomas M Weiss, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syntaxin1a variants lacking an N-peptide or bearing the LE mutation bind to Munc18a in a closed conformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1303753110"}], "href": "https://doi.org/10.1073/pnas.1303753110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23858467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23858467"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Kazuhiko Nakamura, Ayyappan Anitha, Kazuo Yamada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic and expression analyses reveal elevated expression of syntaxin 1A ( STX1A) in high functioning autism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Neuropsychopharmacol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S1461145708009036"}], "href": "https://doi.org/10.1017/S1461145708009036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18593506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18593506"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Kazuhiko Nakamura, Yasuhide Iwata, Ayyappan Anitha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Replication study of Japanese cohorts supports the role of STX1A in autism susceptibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prog Neuropsychopharmacol Biol Psychiatry (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pnpbp.2010.11.033"}], "href": "https://doi.org/10.1016/j.pnpbp.2010.11.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21118708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21118708"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Maria Virginia Soldovieri, Nadia Boutry-Kryza, Mathieu Milh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel KCNQ2 and KCNQ3 mutations in a large cohort of families with benign neonatal epilepsy: first evidence for an altered channel regulation by syntaxin-1A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22500"}], "href": "https://doi.org/10.1002/humu.22500"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24375629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24375629"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Lisheng Peng, Huisheng Liu, Hongyu Ruan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytotoxicity of botulinum neurotoxins reveals a direct role of syntaxin 1 and SNAP-25 in neuron survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms2462"}], "href": "https://doi.org/10.1038/ncomms2462"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23403573"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23403573"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Elizabeta B Mukaetova-Ladinska, Alina Andras, Joan Milne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synaptic proteins and choline acetyltransferase loss in visual cortex in dementia with Lewy bodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuropathol Exp Neurol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/NEN.0b013e31827c5710"}], "href": "https://doi.org/10.1097/NEN.0b013e31827c5710"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23242284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23242284"}]}]}]}
Synonyms	HPC-1, P35-1, STX1, SYN1A
Proteins	STX1A_HUMAN
NCBI Gene ID	6804
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

STX1A has 10,253 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 120 datasets.

Click the + buttons to view associations for STX1A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

STX1A Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of STX1A gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of STX1A gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of STX1A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of STX1A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of STX1A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of STX1A gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of STX1A gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of STX1A gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of STX1A gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of STX1A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with STX1A gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of STX1A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of STX1A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of STX1A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of STX1A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing STX1A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing STX1A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with STX1A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with STX1A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing STX1A protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of STX1A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with STX1A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with STX1A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with STX1A gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of STX1A protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by STX1A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving STX1A gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with STX1A gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with STX1A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with STX1A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with STX1A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with STX1A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at STX1A gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of STX1A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of STX1A gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing STX1A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with STX1A gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with STX1A gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of STX1A gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with STX1A gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.