EPG5 Gene

Name	ectopic P-granules autophagy protein 5 homolog (C. elegans)
Description	This gene encodes a large coiled coil domain-containing protein that functions in autophagy during starvation conditions. Mutations in this gene cause Vici syndrome. [provided by RefSeq, Aug 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EPG5 is a metazoan‐specific autophagy regulator that plays a pivotal role in the maturation of autophagosomes into degradative autolysosomes. It functions as a Rab7 effector, being recruited to late endosomes/lysosomes to ensure the specific fusion of autophagosomes with the endolysosomal compartment. EPG5 directly interacts with key membrane‐fusion proteins—including members of the SNARE complex, LC3/GABARAP family proteins, and R‐SNAREs—to stabilize and promote the formation of fusogenic trans‐SNARE complexes, a process essential for effective autophagic cargo degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Disruption of EPG5 activity, whether by genetic mutations or altered post‐translational modifications such as aberrant ubiquitination, results in a profound block of autophagic flux due to impaired autophagosome–lysosome fusion. This defect leads to the pathological accumulation of undegraded cargo and is the underlying cause of the multisystem disorder Vici syndrome, which manifests with neurodevelopmental abnormalities, immunodeficiency, cardiomyopathy, and muscle pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, studies in embryonic stem cells have revealed that EPG5 is highly expressed and contributes to the maintenance of stemness by ensuring proper autophagic flux. Structural analyses indicate that human EPG5 adopts an extended “shepherd's staff” conformation that preferentially binds components of the GABARAP subfamily, a binding that is further enhanced by deubiquitination events mediated by enzymes such as USP8."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, genetic studies in invertebrate models have consolidated the view that EPG5 functions in a distinct step of the autophagic process—specifically at the point of autolysosome formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings establish EPG5 as a key mediator of autophagosome maturation whose normal function is crucial for cellular homeostasis. Its role as a tether and facilitator of SNARE complex assembly underscores its importance in ensuring efficient autophagic clearance, with its dysfunction contributing directly to the pathogenesis of Vici syndrome and related neurodevelopmental disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zheng Wang, Guangyan Miao, Xue Xue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Vici Syndrome Protein EPG5 Is a Rab7 Effector that Determines the Fusion Specificity of Autophagosomes with Late Endosomes/Lysosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2016.08.021"}], "href": "https://doi.org/10.1016/j.molcel.2016.08.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27588602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27588602"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Thomas Cullup, Ay Lin Kho, Carlo Dionisi-Vici, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2497"}], "href": "https://doi.org/10.1038/ng.2497"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23222957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23222957"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hongyu Zhao, Yan G Zhao, Xingwei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201211014"}], "href": "https://doi.org/10.1083/jcb.201211014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23479740"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23479740"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ikumi Hori, Takanobu Otomo, Mitsuko Nakashima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-02840-8"}], "href": "https://doi.org/10.1038/s41598-017-02840-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28615637"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28615637"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Haifeng Gu, Xingxing Shi, Chao Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USP8 maintains embryonic stem cell stemness via deubiquitination of EPG5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-09430-4"}], "href": "https://doi.org/10.1038/s41467-019-09430-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30931944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30931944"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sung-Eun Nam, Yiu Wing Sunny Cheung, Thanh Ngoc Nguyen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insights on autophagosome-lysosome tethering from structural and biochemical characterization of human autophagy factor EPG5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Commun Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42003-021-01830-x"}], "href": "https://doi.org/10.1038/s42003-021-01830-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33674710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33674710"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ye Tian, Zhipeng Li, Wanqiu Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C. elegans screen identifies autophagy genes specific to multicellular organisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2010.04.034"}], "href": "https://doi.org/10.1016/j.cell.2010.04.034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20550938"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20550938"}]}]}]}
Synonyms	VICIS, HEPG5, KIAA1632, HEEW1
Proteins	EPG5_HUMAN
NCBI Gene ID	57724
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EPG5 has 5,220 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 111 datasets.

Click the + buttons to view associations for EPG5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EPG5 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 EPG5 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 EPG5 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 EPG5 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 EPG5 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 EPG5 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 EPG5 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 EPG5 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 EPG5 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 EPG5 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 EPG5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EPG5 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with EPG5 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 EPG5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EPG5 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 EPG5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with EPG5 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with EPG5 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing EPG5 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EPG5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing EPG5 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 EPG5 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 EPG5 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 EPG5 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 EPG5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EPG5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EPG5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EPG5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of EPG5 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 EPG5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving EPG5 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving EPG5 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with EPG5 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 EPG5 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 EPG5 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 EPG5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EPG5 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 EPG5 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 EPG5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of EPG5 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 EPG5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.