HGS (Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate)
A key regulator of endosomal sorting and signaling, implicated in cancer and neurodegenerative diseases.
Gene Information Card
| Symbol | HGS |
|---|---|
| Full Name | Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 9146 ncbi.nlm.nih.gov/gene/9146 |
| Ensembl ID | ENSG00000185359 |
| UniProt ID | O14964 |
| OMIM ID | 604333 |
| HGNC ID | 4897 |
| Aliases | HRS, HGS_HUMAN, VPS27 |
Description
HGS encodes a protein that functions as a component of the ESCRT-0 complex, essential for sorting ubiquitinated membrane proteins into multivesicular bodies for lysosomal degradation. It regulates receptor tyrosine kinase signaling, particularly hepatocyte growth factor (HGF) signaling, and is involved in endosomal trafficking, autophagy, and cell proliferation. Dysregulation of HGS is linked to various cancers and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression or mutation leads to altered endosomal sorting and sustained growth factor signaling | NCBI Gene, COSMIC |
| Neurodegenerative diseases | Impaired autophagy and accumulation of protein aggregates due to HGS dysfunction | UniProt, OMIM |
| Developmental disorders | Rare variants associated with syndromic features | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 15.2 | Medium |
| Kidney | 10.1 | Medium |
| Testis | 18.7 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.5 | Cervical cancer cell line |
| HEK293 | 11.2 | Embryonic kidney cells |
| A549 | 9.8 | Lung carcinoma |
| MCF7 | 13.0 | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112G>A (p.Glu38Lys) | Missense | <0.1% | Unknown |
| c.456_457insA | Frameshift | <0.1% | Loss of function |
| c.789C>T (p.Arg263Trp) | Missense | <0.1% | Unknown |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations predicted to truncate the protein, impairing ESCRT-0 function.
Gain of Function (GOF)
Not well documented; overexpression in tumors may act as a gain-of-function by enhancing receptor recycling.
Dominant Negative (DN)
Missense mutations in the VHS domain may interfere with ubiquitin binding, disrupting normal sorting.
View complete mutation data：
Gene Ontology (GO)
| • Endosomal transport | • Protein ubiquitination |
| • Intracellular protein transport | • Autophagy |
| • Signal transduction |
Pathways
• ESCRT pathway
• Endocytosis
• HGF signaling
• Autophagy
Protein Summary
The HGS protein (also known as HRS) is a 777-amino acid component of the ESCRT-0 complex. It contains a VHS domain, a FYVE zinc finger domain that binds phosphatidylinositol 3-phosphate, and a ubiquitin-interacting motif. It localizes to early endosomes and recruits clathrin and other ESCRT components to sort ubiquitinated cargo for lysosomal degradation. HGS also interacts with STAM proteins and regulates signaling from receptor tyrosine kinases such as EGFR and Met.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HGSNAT Knockout HEK293 Cell Line | EDJ-KQ2968 | Human | 138050 | Details Get a Quote |
| HGSNAT Knockout A-549 Cell Line | EDJ-KQ24125 | Human | 138050 | Details Get a Quote |
| HGSNAT Knockout HeLa Cell Line | EDJ-KQ24127 | Human | 138050 | Details Get a Quote |
| HGSNAT Knockout HCT 116 Cell Line | EDJ-KQ22755 | Human | 138050 | Details Get a Quote |
