VAC14 Gene

Name	Vac14 homolog (S. cerevisiae)
Description	This gene encodes a scaffold protein that is a component of the PIKfyve protein kinase complex. This complex is responsible for the synthesis of phosphatidylinositol 3,5-bisphosphate, an important component of cellular membranes, from phosphatidylinositol 3-phosphate. Mice lacking a functional copy of this gene exhibit severe neurodegeneration. Mutations in the human gene have been identified in patients with a childhood onset progressive neurological disorder characterized by impaired movement, dystonia, and striatal abnormalities. [provided by RefSeq, May 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nVAC14 is a highly conserved scaffold protein that plays a pivotal role in regulating phosphatidylinositol 3,5‐bisphosphate [PI(3,5)P2] metabolism by organizing a multiprotein complex with the lipid kinase PIKfyve and its antagonistic phosphatases (such as FIG4 or Sac3). This complex is essential for maintaining proper endosomal and lysosomal dynamics, as VAC14 activates PIKfyve enzymatic activity to control membrane trafficking and the morphology of endocytic organelles—a function observed from yeast to mammalian cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n \n \nIn addition to its biochemical role, pathogenic variants in VAC14 have been linked to severe neurodegenerative conditions. Disruption of VAC14 function results in aberrant PI(3,5)P2 levels and the accumulation of intracellular vacuoles in affected cells, which is associated with childhood‐onset disorders such as striatonigral degeneration, Yunis‐Varón syndrome, and dystonia. These studies underscore that loss‐of‐function or missense mutations in VAC14 can lead to rapid neurological regression and profound neuronal vacuolation, thereby highlighting its critical importance in neural homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n \n \nBeyond its canonical role in PI(3,5)P2 synthesis and endosomal trafficking, VAC14 engages in novel protein–protein interactions that broaden its functional repertoire. For example, VAC14 interacts with the PDZ domain of neuronal nitric oxide synthase through an atypical internal motif, and proteomic studies have revealed links to components of vesicular trafficking (such as COPI subunits) and regulators of cell signaling. Moreover, emerging evidence shows that VAC14 influences tissue‐specific processes, such as endocytic handling in renal epithelia and pathways affecting melanoma progression. These findings suggest that VAC14 acts not only as a critical regulator of phosphoinositide metabolism but also as a multifunctional scaffold integrating intracellular trafficking with diverse signal transduction networks."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Diego Sbrissa, Ognian C Ikonomov, Zhiyao Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate synthesis and turnover that regulates the progression of endosomal transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex."}]}, {"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.M611678200"}], "href": "https://doi.org/10.1074/jbc.M611678200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17556371"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17556371"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Diego Sbrissa, Ognian C Ikonomov, Jana Strakova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A mammalian ortholog of Saccharomyces cerevisiae Vac14 that associates with and up-regulates PIKfyve phosphoinositide 5-kinase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.24.23.10437-10447.2004"}], "href": "https://doi.org/10.1128/MCB.24.23.10437-10447.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15542851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15542851"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ulf Schulze, Beate Vollenbröker, Daniela A Braun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Vac14-interaction network is linked to regulators of the endolysosomal and autophagic pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M113.034108"}], "href": "https://doi.org/10.1074/mcp.M113.034108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24578385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24578385"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Monica I Alvarez, Luke C Glover, Peter Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human genetic variation in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "VAC14"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " regulates "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Salmonella"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " invasion and typhoid fever through modulation of cholesterol."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1706070114"}], "href": "https://doi.org/10.1073/pnas.1706070114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28827342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28827342"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shuang Liao, Tingting Chen, Ying Dai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel VAC14 variants identified in two Chinese siblings with childhood-onset striatonigral degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomic Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mgg3.1101"}], "href": "https://doi.org/10.1002/mgg3.1101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31876398"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31876398"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Parneet Kaur, Gandham SriLakshmi Bhavani, Arun Raj, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homozygous variant, p.(Arg643Trp) in VAC14 causes striatonigral degeneration: report of a novel variant and review of VAC14-related disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s10038-019-0678-1"}], "href": "https://doi.org/10.1038/s10038-019-0678-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31591492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31591492"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hauke Baumann, Sinem Tunc, Albrecht Günther, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered homodimer formation and increased iron accumulation in VAC14-related disease: Case report and review of the literature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Parkinsonism Relat Disord (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.parkreldis.2020.09.012"}], "href": "https://doi.org/10.1016/j.parkreldis.2020.09.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32949958"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32949958"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Louisa Mayer, Maria Jasztal, Mercedes Pardo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nbeal2 interacts with Dock7, Sec16a, and Vac14."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2017-08-800359"}], "href": "https://doi.org/10.1182/blood-2017-08-800359"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29187380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29187380"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Shirley Qiu, Mathieu Lavallée-Adam, Marceline Côté "}, {"type": "b", "children": [{"type": "t", "text": "Proximity Interactome Map of the Vac14-Fig4 Complex Using BioID."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Proteome Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.jproteome.1c00408"}], "href": "https://doi.org/10.1021/acs.jproteome.1c00408"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34554760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34554760"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ulf Michgehl, Boris V Skryabin, Samet Bayraktar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nephron-specific knockin of the PIKfyve-binding-deficient Vac14"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "L156R"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " mutant results in albuminuria and mesangial expansion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00191.2018"}], "href": "https://doi.org/10.1152/ajprenal.00191.2018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30066585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30066585"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Chun-Hua Wang, Lu-Kai Wang, Chang-Chieh Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIG1 Inhibits the mTOR Signaling Pathway in Malignant Melanoma Through the VAC14 Protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21873/anticanres.16430"}], "href": "https://doi.org/10.21873/anticanres.16430"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37247911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37247911"}]}]}]}
Synonyms	TAX1BP2, ARPIKFYVE
Proteins	VAC14_HUMAN
NCBI Gene ID	55697
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

VAC14 has 7,435 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 125 datasets.

Click the + buttons to view associations for VAC14 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

VAC14 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 VAC14 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 VAC14 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of VAC14 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of VAC14 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 VAC14 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 VAC14 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 VAC14 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 VAC14 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 VAC14 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of VAC14 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of VAC14 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 VAC14 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with VAC14 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with VAC14 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 VAC14 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of VAC14 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 VAC14 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with VAC14 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing VAC14 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of VAC14 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing VAC14 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing VAC14 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with VAC14 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 VAC14 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 VAC14 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with VAC14 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with VAC14 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with VAC14 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with VAC14 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 VAC14 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 VAC14 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving VAC14 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with VAC14 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 VAC14 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 VAC14 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 VAC14 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with VAC14 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 VAC14 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 VAC14 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of VAC14 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.