VPS4B Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the VPS4B gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | VPS4B |
|---|---|
| Full Name | Vacuolar protein sorting 4 homolog B |
| Gene Type | Protein coding |
| Chromosomal Location | 18q21.33 |
| NCBI Gene ID | 9525 ncbi.nlm.nih.gov/gene/9525 |
| Ensembl ID | ENSG00000118689 |
| UniProt ID | O75351 |
| OMIM ID | 609982 |
| HGNC ID | 12718 |
| Aliases | MIG1, VPS4, VPS4-2, CGI-628 |
Description
The VPS4B gene encodes a member of the AAA ATPase family, specifically the VPS4 (vacuolar protein sorting 4) subfamily. This protein is essential for the function of the endosomal sorting complex required for transport (ESCRT) pathway, which is involved in multivesicular body (MVB) formation, cytokinesis, and enveloped virus budding. VPS4B provides the ATPase activity that disassembles ESCRT-III complexes after cargo sorting, allowing the recycling of ESCRT components. Mutations in VPS4B have been linked to various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Microcephaly, short stature, and impaired glucose metabolism (MSSG) | Biallelic loss-of-function mutations in VPS4B impair ESCRT-III disassembly, leading to defective cytokinesis and cell proliferation, affecting brain development and growth. | ClinVar, OMIM |
| Cancer (various types) | Altered VPS4B expression or mutations can disrupt ESCRT function, affecting receptor downregulation, cell signaling, and genomic stability, contributing to tumorigenesis. | COSMIC, PubMed |
| Neurodegenerative disorders (potential) | Impaired ESCRT function due to VPS4B dysfunction may lead to accumulation of protein aggregates and autophagic defects, contributing to neurodegeneration. | PubMed (hypothetical) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Bone marrow | High | High |
| Lymph node | High | High |
| Spleen | High | High |
| Brain | Medium | Medium |
| Liver | Medium | Medium |
| Kidney | Medium | Medium |
| Heart | Low | Low |
| Skeletal muscle | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HeLa (cervical cancer) | High | Strong expression; used in functional studies of ESCRT. |
| HEK293 (embryonic kidney) | High | Commonly used for overexpression studies. |
| HepG2 (liver cancer) | Medium | Moderate expression. |
| A549 (lung cancer) | Medium | Moderate expression. |
| MCF7 (breast cancer) | Low | Lower expression compared to other lines. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.850C>T (p.Arg284*) | Nonsense | Rare (in MSSG) | Premature stop codon, loss of function. |
| c.1129C>T (p.Arg377*) | Nonsense | Rare (in MSSG) | Premature stop codon, loss of function. |
| c.1045G>A (p.Gly349Arg) | Missense | Rare (in cancer) | Disrupts ATPase activity, dominant-negative effect. |
| c.1180A>G (p.Thr394Ala) | Missense | Rare (in cancer) | Alters protein stability, potential loss of function. |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated proteins or reduced expression are classified as loss-of-function. These impair ESCRT-III disassembly, causing defects in MVB formation and cytokinesis.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for VPS4B. Most pathogenic mutations are loss-of-function or dominant-negative.
Dominant Negative (DN)
Missense mutations in the ATPase domain (e.g., p.Gly349Arg) can act as dominant-negative by forming inactive oligomers with wild-type protein, disrupting normal VPS4B function.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • ATP hydrolysis activity |
| • protein homodimerization activity | • identical protein binding |
| • microtubule binding | • protein domain specific binding |
| • cytoplasm | • cytosol |
| • endosome | • midbody |
| • nucleus | • plasma membrane |
| • ESCRT complex | • vacuolar membrane |
| • cytokinesis | • endosomal transport |
| • multivesicular body sorting | • protein catabolic process |
| • viral budding | • cell division |
| • regulation of cell cycle |
Pathways
• ESCRT pathway
• Multivesicular body (MVB) sorting pathway
• Cytokinesis
• Viral budding (e.g.
• HIV-1)
• Autophagy (regulation)
Protein Summary
The VPS4B protein is a 437-amino acid AAA ATPase that forms a homo-oligomeric ring structure. It binds to ESCRT-III subunits via its MIT (microtubule-interacting and transport) domain and uses ATP hydrolysis to remodel and disassemble ESCRT-III filaments, a critical step in membrane scission events. VPS4B is involved in multiple cellular processes including endosomal sorting, cytokinesis, and exosome biogenesis. Its dysfunction is linked to developmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS4B Knockout HEK293 Cell Line | EDJ-KQ6625 | Human | 9525 | Details Get a Quote |
| VPS4B Knockout HCT 116 Cell Line | EDJ-KQ18269 | Human | 9525 | Details Get a Quote |
| VPS4B Knockout A-549 Cell Line | EDJ-KQ30870 | Human | 9525 | Details Get a Quote |
| VPS4B Knockout HeLa Cell Line | EDJ-KQ30871 | Human | 9525 | Details Get a Quote |
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