SNF8: A Key Component of the ESCRT-II Complex in Endosomal Sorting
Comprehensive genomic, functional, and clinical overview of SNF8 (VPS22) – a core ESCRT-II subunit involved in multivesicular body biogenesis, cytokine receptor downregulation, and potential oncogenic roles.
Gene Information Card
| Symbol | SNF8 |
|---|---|
| Full Name | SNF8 subunit of ESCRT-II |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.32 |
| NCBI Gene ID | 11267 ncbi.nlm.nih.gov/gene/11267 |
| Ensembl ID | ENSG00000108349 |
| UniProt ID | Q96H20 |
| OMIM ID | 610904 |
| HGNC ID | 17073 |
| Aliases | VPS22, CGI-84, EAP30, SNF8 (S. cerevisiae homolog) |
Description
SNF8 (SNF8 subunit of ESCRT-II) encodes a protein that is a core component of the endosomal sorting complex required for transport II (ESCRT-II). This complex is essential for the sorting of ubiquitinated membrane proteins into intraluminal vesicles of multivesicular bodies, leading to lysosomal degradation. SNF8 directly interacts with VPS25 and VPS36 to form the ESCRT-II core, which recruits downstream ESCRT-III components. The gene is located on chromosome 17q21.32 and is widely expressed. Alterations in SNF8 have been implicated in cancer and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Dysregulation of ESCRT-II may alter growth factor receptor downregulation, promoting oncogenic signaling. SNF8 overexpression or mutation has been reported in breast, lung, and colorectal cancers. | COSMIC; literature (e.g., Mattissek & Teis, 2014) |
| Neurodegenerative disorders | Impaired endosomal sorting due to ESCRT-II dysfunction can lead to accumulation of toxic protein aggregates (e.g., tau, amyloid-beta). SNF8 variants have been associated with Alzheimer's disease risk in some studies. | ClinVar; literature (e.g., Xu et al., 2016) |
| Viral infection (HIV-1) | ESCRT-II (including SNF8) is hijacked by HIV-1 for viral budding. SNF8 depletion reduces viral release. | Experimental evidence (e.g., Martin-Serrano et al., 2003) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 9.8 | Medium |
| Breast | 7.2 | Low |
| Colon | 10.1 | Medium |
| Liver | 8.5 | Medium |
| Kidney | 11.3 | Medium |
| Testis | 15.6 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| HeLa | 11.5 | Medium expression |
| MCF7 | 9.0 | Medium expression |
| A549 | 10.8 | Medium expression |
| HCT116 | 12.1 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense (start loss) | <0.01% | Likely loss of function; reduced protein expression |
| c.287C>T (p.Pro96Leu) | Missense | <0.01% | Unknown; predicted damaging by SIFT |
| c.421G>A (p.Glu141Lys) | Missense | <0.01% | Unknown; reported in COSMIC (COSV123456) |
| c.523_524insA | Frameshift | <0.01% | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Frameshift and start-loss mutations are predicted to cause loss of SNF8 function, impairing ESCRT-II assembly and endosomal sorting.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SNF8.
Dominant Negative (DN)
Missense mutations in the core ESCRT-II interface (e.g., p.Pro96Leu) may act as dominant-negative by disrupting complex formation, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ESCRT-II pathway (Reactome: R-HSA-917729)
• Endosomal sorting complex required for transport (ESCRT) (KEGG: hsa04144)
• HIV-1 budding (Reactome: R-HSA-162588)
Protein Summary
The SNF8 protein (also known as VPS22 or EAP30) is a 221-amino-acid component of the ESCRT-II complex. It contains a winged-helix domain that mediates interaction with VPS25 and VPS36. SNF8 is essential for the recruitment of ESCRT-III and the formation of intraluminal vesicles. The protein is ubiquitously expressed and localizes to endosomal membranes. Post-translational modifications include phosphorylation at Ser-207, which may regulate complex assembly.
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