VPS36: ESCRT-II Subunit in Endosomal Sorting and Cancer
Explore the VPS36 gene, its role in the ESCRT pathway, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | VPS36 |
|---|---|
| Full Name | VPS36 subunit of ESCRT-II |
| Gene Type | protein-coding |
| Chromosomal Location | 13q14.3 |
| NCBI Gene ID | 51028 ncbi.nlm.nih.gov/gene/51028 |
| Ensembl ID | ENSG00000102547 |
| UniProt ID | Q86VN1 |
| OMIM ID | 610903 |
| HGNC ID | 24948 |
| Aliases | C13orf9, CGI-145, ESCRT-II complex subunit VPS36 |
Description
VPS36 encodes a subunit of the endosomal sorting complex required for transport II (ESCRT-II), which is essential for sorting ubiquitinated membrane proteins into multivesicular bodies for lysosomal degradation. The protein contains a GLUE domain that binds ubiquitin and phosphoinositides, facilitating cargo recognition. VPS36 is involved in cytokinesis, autophagy, and HIV-1 budding. Mutations and altered expression have been linked to various cancers and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered VPS36 expression disrupts ESCRT-mediated degradation of growth factor receptors, promoting oncogenic signaling. | COSMIC; TCGA data show copy number alterations and differential expression in multiple cancer types. |
| Neurodegenerative disorders | Impaired ESCRT function leads to accumulation of ubiquitinated proteins and autophagic dysfunction. | Studies in model organisms; ClinVar reports variants of uncertain significance. |
| Viral infection (HIV-1) | VPS36 interacts with viral Gag protein to facilitate viral budding; dysregulation may affect infectivity. | Published research; UniProt annotation. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Lung | 8.7 | Low |
| Liver | 6.2 | Low |
| Kidney | 9.5 | Medium |
| Testis | 15.1 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.2 | Cervical cancer cell line; moderate expression |
| HepG2 | 7.8 | Liver cancer cell line; low expression |
| A549 | 9.0 | Lung carcinoma; moderate expression |
| K562 | 11.5 | Leukemia cell line; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1132C>T (p.Arg378Trp) | Missense | 0.01% (gnomAD) | May affect protein stability; ClinVar uncertain significance. |
| c.154G>A (p.Glu52Lys) | Missense | 0.005% | Located in GLUE domain; potential impact on ubiquitin binding. |
| c.789_790del (p.Glu264fs) | Frameshift | Rare | Predicted loss-of-function; associated with disease risk in some studies. |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations leading to truncated protein or nonsense-mediated decay, impairing ESCRT-II function.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression may contribute to tumor progression.
Dominant Negative (DN)
Missense mutations in the GLUE domain may interfere with complex assembly, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • protein transport | • endosomal transport |
| • ubiquitin binding | • phosphatidylinositol binding |
| • ESCRT complex | • multivesicular body sorting |
Pathways
• ESCRT pathway
• Endosomal sorting
• Autophagy
• Cytokinesis
• Viral budding
Protein Summary
VPS36 is a 375-amino acid protein that forms part of the ESCRT-II complex, which consists of VPS36, VPS22, and VPS25. The N-terminal GLUE domain binds ubiquitin and phosphatidylinositol 3,5-bisphosphate, targeting the complex to endosomal membranes. VPS36 also interacts with ESCRT-I and ESCRT-III components to facilitate vesicle formation. It is ubiquitously expressed but enriched in testis and brain. Post-translational modifications include phosphorylation, which may regulate its function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS36 Knockout HEK293 Cell Line | EDJ-KQ10876 | Human | 51028 | Details Get a Quote |
| VPS36 Knockout A-549 Cell Line | EDJ-KQ38559 | Human | 51028 | Details Get a Quote |
| VPS36 Knockout HCT 116 Cell Line | EDJ-KQ38560 | Human | 51028 | Details Get a Quote |
| VPS36 Knockout HeLa Cell Line | EDJ-KQ38561 | Human | 51028 | Details Get a Quote |
