GAPVD1 Gene

HGNC Family	VPS9 domain containing
Name	GTPase activating protein and VPS9 domains 1
Description	Enables GTPase activating protein binding activity and guanyl-nucleotide exchange factor activity. Involved in regulation of protein transport. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GAPVD1 (also known as GAPex‐5) is emerging as a critical regulator of endocytic trafficking through its function as a guanine nucleotide exchange factor (GEF) for Rab5 and related GTPases. Several studies have demonstrated that GAPVD1 is essential for activating Rab5 during key cellular events. For example, during apoptotic cell engulfment, GAPVD1 is recruited via microtubule‐associated mechanisms to phagosomes where it promotes a transient activation of Rab5 required for phagosome maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In insulin‐responsive cells, GAPVD1 plays a central role in mediating insulin‐stimulated signaling; it facilitates the recruitment and activation of Rab5, thereby contributing to phosphatidylinositol 3‐phosphate production and Glut4 vesicle trafficking, which are critical for effective glucose uptake."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in insulin signaling, GAPVD1 has been implicated in receptor-mediated endocytosis. Its activity influences the ubiquitination and subsequent trafficking of the epidermal growth factor receptor (EGFR), thereby regulating receptor degradation and endosome fusion independent of direct Rab5 activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, GAPVD1 itself is a substrate for kinases such as casein kinase 1δ/ε, and its phosphorylation status modulates its ability to support efficient endocytosis and vesicle recycling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Broader phylogenetic and functional studies have placed GAPVD1 within an evolutionarily conserved family of Vps9 domain–containing proteins that regulate Rab5-dependent membrane transport, thereby impacting diverse physiological and pathological processes, including metabolic regulation and even pathogen-host interactions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings reveal that GAPVD1 integrates upstream signaling cues with endocytic mechanisms by activating Rab5, thus ensuring proper receptor trafficking, membrane recycling, and cellular homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masahiro Kitano, Michio Nakaya, Takeshi Nakamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Imaging of Rab5 activity identifies essential regulators for phagosome maturation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06857"}], "href": "https://doi.org/10.1038/nature06857"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18385674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18385674"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Irfan J Lodhi, Shian-Huey Chiang, Louise Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gapex-5, a Rab31 guanine nucleotide exchange factor that regulates Glut4 trafficking in adipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2006.12.006"}], "href": "https://doi.org/10.1016/j.cmet.2006.12.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17189207"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17189207"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiong Su, Irfan J Lodhi, Alan R Saltiel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insulin-stimulated Interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B/Akt require Rab5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M602873200"}], "href": "https://doi.org/10.1074/jbc.M602873200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16880210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16880210"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Irfan J Lodhi, Dave Bridges, Shian-Huey Chiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insulin stimulates phosphatidylinositol 3-phosphate production via the activation of Rab5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e08-01-0105"}], "href": "https://doi.org/10.1091/mbc.e08-01-0105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18434594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18434594"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xiong Su, Chen Kong, Philip D Stahl "}, {"type": "b", "children": [{"type": "t", "text": "GAPex-5 mediates ubiquitination, trafficking, and degradation of epidermal growth factor receptor."}]}, {"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.M703725200"}], "href": "https://doi.org/10.1074/jbc.M703725200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17545148"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17545148"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rodrigo X Guillen, Janel R Beckley, Jun-Song Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRISPR-mediated gene targeting of CK1δ/ε leads to enhanced understanding of their role in endocytosis via phosphoregulation of GAPVD1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-63669-2"}], "href": "https://doi.org/10.1038/s41598-020-63669-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32321936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32321936"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Emily K Herman, Moazzam Ali, Mark C Field, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of early endosomes across eukaryotes: Evolution and functional homology of Vps9 proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/tra.12570"}], "href": "https://doi.org/10.1111/tra.12570"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29603841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29603841"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Mitchell B Batty, Ralf B Schittenhelm, Dominique Dorin-Semblat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of Plasmodium falciparum casein kinase 1 with components of host cell protein trafficking machinery."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "IUBMB Life (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/iub.2294"}], "href": "https://doi.org/10.1002/iub.2294"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32356940"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32356940"}]}]}]}
Synonyms	GAPEX-5, GAPEX5, RAP6
Proteins	GAPD1_HUMAN
NCBI Gene ID	26130
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GAPVD1 has 7,239 functional associations with biological entities spanning 9 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, sequence feature) extracted from 125 datasets.

Click the + buttons to view associations for GAPVD1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GAPVD1 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 GAPVD1 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 GAPVD1 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 GAPVD1 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 GAPVD1 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 GAPVD1 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 GAPVD1 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 GAPVD1 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 GAPVD1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of GAPVD1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GAPVD1 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 GAPVD1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with GAPVD1 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GAPVD1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GAPVD1 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 GAPVD1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of GAPVD1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing GAPVD1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GAPVD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing GAPVD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing GAPVD1 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 GAPVD1 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 GAPVD1 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 GAPVD1 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 GAPVD1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GAPVD1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GAPVD1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GAPVD1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with GAPVD1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by GAPVD1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for GAPVD1 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with GAPVD1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with GAPVD1 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 GAPVD1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at GAPVD1 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 GAPVD1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GAPVD1 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 GAPVD1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with GAPVD1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of GAPVD1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with GAPVD1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.