STXBP4 Gene

Name	syntaxin binding protein 4
Description	Enables syntaxin binding activity. Involved in several processes, including positive regulation of cell cycle G1/S phase transition; positive regulation of keratinocyte proliferation; and protein stabilization. Located in extracellular exosome. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSTXBP4 is emerging as a multifunctional regulatory protein with critical roles in cancer biology. In stratified epithelial cells, STXBP4 directly interacts with ΔNp63, acting as a stabilizer by preventing its degradation via the ubiquitin–proteasome pathway. Under normal growth conditions, STXBP4 maintains high basal levels of ΔNp63, whereas its downregulation upon genotoxic stress permits ΔNp63 destabilization—a dynamic that impacts cell differentiation and tumorigenic potential. This regulatory function has been demonstrated in squamous cell carcinomas, including lung SCC, where high STXBP4 expression correlates with enhanced ΔNp63 accumulation and more aggressive tumor characteristics."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in modulating ΔNp63 stability, STXBP4 has been identified as a negative regulator within the Hippo pathway. By assembling a multiprotein complex that includes α-catenin and several PY motif-containing regulators, STXBP4 inhibits the activity of the YAP transcriptional coactivator in an actin cytoskeleton tension‐dependent manner. This function suggests that, in certain cellular contexts such as human kidney cancer, STXBP4 may serve as a tumor suppressor by restraining YAP-driven oncogenic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies further underscore the potential oncogenic implications of altered STXBP4 expression. Fine-mapping of breast cancer susceptibility loci has identified risk variants within intronic regions of the STXBP4 gene, many of which are linked to increased gene expression in breast tumors. Additionally, deleterious noncoding SNP analyses have implicated dysregulation of STXBP4 in breast cancer development, while meta-analyses of the STXBP4/COX11 polymorphism have investigated its association with breast cancer risk. Together, these data indicate that aberrant regulation of STXBP4 not only influences key protein quality control mechanisms but may also contribute to cancer susceptibility through its impact on epithelial cell homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yingchun Li, Melissa J Peart, Carol Prives "}, {"type": "b", "children": [{"type": "t", "text": "Stxbp4 regulates DeltaNp63 stability by suppression of RACK1-dependent degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00449-09"}], "href": "https://doi.org/10.1128/MCB.00449-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19451233"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19451233"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Susumu Rokudai, Yingchun Li, Yukihiro Otaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STXBP4 regulates APC/C-mediated p63 turnover and drives squamous cell carcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1718546115"}], "href": "https://doi.org/10.1073/pnas.1718546115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29735662"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29735662"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yukihiro Otaka, Susumu Rokudai, Kyoichi Kaira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STXBP4 Drives Tumor Growth and Is Associated with Poor Prognosis through PDGF Receptor Signaling in Lung Squamous Cell Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-16-1815"}], "href": "https://doi.org/10.1158/1078-0432.CCR-16-1815"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28087642"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28087642"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Erkhem-Ochir Bilguun, Kyoichi Kaira, Reika Kawabata-Iwakawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinctive roles of syntaxin binding protein 4 and its action target, TP63, in lung squamous cell carcinoma: a theranostic study for the precision medicine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12885-020-07448-2"}], "href": "https://doi.org/10.1186/s12885-020-07448-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32993587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32993587"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rebecca E Vargas, Vy Thuy Duong, Han Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elucidation of WW domain ligand binding specificities in the Hippo pathway reveals STXBP4 as YAP inhibitor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.2019102406"}], "href": "https://doi.org/10.15252/embj.2019102406"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31782549"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31782549"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lin Tang, Jing Xu, Feng Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of STXBP4/COX11 rs6504950 (G>A) polymorphism with breast cancer risk: evidence from 17,960 cases and 22,713 controls."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Med Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.arcmed.2012.07.008"}], "href": "https://doi.org/10.1016/j.arcmed.2012.07.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22863968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22863968"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hatef Darabi, Jonathan Beesley, Arnaud Droit, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep32512"}], "href": "https://doi.org/10.1038/srep32512"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27600471"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27600471"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Tariq Ahmad Masoodi, Babajan Banaganapalli, Venkatesh Vaidyanathan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Computational Analysis of Breast Cancer GWAS Loci Identifies the Putative Deleterious Effect of STXBP4 and ZNF404 Gene Variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.26080"}], "href": "https://doi.org/10.1002/jcb.26080"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28422318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28422318"}]}]}]}
Synonyms	SYNIP
Proteins	STXB4_HUMAN
NCBI Gene ID	252983
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

STXBP4 has 4,629 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 110 datasets.

Click the + buttons to view associations for STXBP4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

STXBP4 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 STXBP4 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 STXBP4 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 STXBP4 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 STXBP4 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 STXBP4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of STXBP4 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 STXBP4 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 STXBP4 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 STXBP4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with STXBP4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with STXBP4 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 STXBP4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of STXBP4 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 STXBP4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing STXBP4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing STXBP4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing STXBP4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with STXBP4 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 STXBP4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of STXBP4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with STXBP4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with STXBP4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with STXBP4 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of STXBP4 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 STXBP4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with STXBP4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with STXBP4 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 STXBP4 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 STXBP4 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 STXBP4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with STXBP4 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 STXBP4 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 STXBP4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of STXBP4 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 STXBP4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with STXBP4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with STXBP4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with STXBP4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing STXBP4 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of STXBP4 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.