HGS Gene

HGNC Family	Zinc fingers
Name	hepatocyte growth factor-regulated tyrosine kinase substrate
Description	The protein encoded by this gene regulates endosomal sorting and plays a critical role in the recycling and degradation of membrane receptors. The encoded protein sorts monoubiquitinated membrane proteins into the multivesicular body, targeting these proteins for lysosome-dependent degradation. [provided by RefSeq, Dec 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Hepatocyte growth factor‐regulated tyrosine kinase substrate (HGS, also known as Hrs) is a key component of the endosomal sorting machinery that functions chiefly within the ESCRT‐0 complex. HGS recognizes and binds ubiquitinated cargo at early endosomes, thereby sequestering activated membrane receptors and other ubiquitin‐modified proteins into domains destined for intraluminal vesicle formation in multivesicular bodies. This process is critical for the down‐regulation of signaling receptors and for directing cargo toward lysosomal degradation. In several studies, HGS has been shown to mediate the sorting events that allow proper phagosome maturation and receptor recycling, and its interaction with pathogen‐derived effectors can disrupt these pathways to promote intracellular bacterial survival. In addition, HGS participates in the regulation of receptor trafficking by modulating the ubiquitination status of key endosomal proteins, influencing downstream signaling events and contributing to cellular homeostasis. Disruption of HGS function has been associated with altered endosomal dynamics that may facilitate disease progression, as exemplified by its role in impaired lysosomal targeting of pathogens, defective receptor recycling, and altered viral release. Collectively, these findings illustrate that HGS is indispensable for the precise control of endosomal cargo sorting and degradation, thereby tuning cellular responses to extracellular stimuli."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alka Mehra, Aleena Zahra, Victor Thompson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mycobacterium tuberculosis type VII secreted effector EsxH targets host ESCRT to impair trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1003734"}], "href": "https://doi.org/10.1371/journal.ppat.1003734"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24204276"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24204276"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rohit Malik, Adriano Marchese "}, {"type": "b", "children": [{"type": "t", "text": "Arrestin-2 interacts with the endosomal sorting complex required for transport machinery to modulate endosomal sorting of CXCR4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e10-02-0169"}], "href": "https://doi.org/10.1091/mbc.e10-02-0169"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20505072"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20505072"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Etienne Morel, Zeina Chamoun, Zofia M Lasiecka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphatidylinositol-3-phosphate regulates sorting and processing of amyloid precursor protein through the endosomal system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms3250"}], "href": "https://doi.org/10.1038/ncomms3250"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23907271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23907271"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rong Rong, Ezequiel I Surace, Carrie A Haipek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serine 518 phosphorylation modulates merlin intramolecular association and binding to critical effectors important for NF2 growth suppression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1207794"}], "href": "https://doi.org/10.1038/sj.onc.1207794"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15378014"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15378014"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Katy Janvier, Annegret Pelchen-Matthews, Jean-Baptiste Renaud, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1001265"}], "href": "https://doi.org/10.1371/journal.ppat.1001265"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21304933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21304933"}]}]}]}
Synonyms	HRS
Proteins	HGS_HUMAN
NCBI Gene ID	9146
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HGS has 8,318 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 126 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

HGS Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by HGS gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HGS 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 HGS 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 HGS 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 HGS 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 HGS 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 HGS 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 HGS 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 HGS 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 HGS 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 HGS 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 HGS gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HGS 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 HGS gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HGS 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 HGS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing HGS 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 HGS gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HGS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HGS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing HGS 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 HGS 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 HGS 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 HGS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing HGS protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of HGS gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HGS gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HGS gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HGS gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with HGS 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 HGS 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 HGS 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 HGS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HGS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for HGS protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HGS 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 HGS gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HGS 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 HGS from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with HGS gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.