VPS33A
VPS33A, CORVET/HOPS complex subunit, associated with mucopolysaccharidosis-like syndrome and retinal dystrophy
Gene Information Card
| Symbol | VPS33A |
|---|---|
| Full Name | VPS33A, CORVET/HOPS complex subunit |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 65082 ncbi.nlm.nih.gov/gene/65082 |
| Ensembl ID | ENSG00000111206 |
| UniProt ID | Q96AX1 |
| OMIM ID | 610036 |
| HGNC ID | 18179 |
| Aliases | VPS33, MPSPS, RP83 |
Description
VPS33A encodes a protein that is a core component of the class C VPS (vacuolar protein sorting) complex, which assembles into the CORVET and HOPS tethering complexes. These complexes are essential for endosomal and lysosomal trafficking, fusion of vesicles with endosomes and lysosomes, and autophagy. Mutations in VPS33A cause a severe multisystem disorder resembling mucopolysaccharidosis, characterized by skeletal abnormalities, intellectual disability, and retinal dystrophy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mucopolysaccharidosis-like syndrome with congenital heart defects and retinal dystrophy (MPSPS) | Loss-of-function mutations impair CORVET/HOPS complex function, disrupting endosomal-lysosomal trafficking and leading to accumulation of undegraded substrates. | PMID: 28397838, ClinVar |
| Retinitis pigmentosa 83 (RP83) | Biallelic missense mutations in VPS33A cause retinal degeneration through defective autophagy and endosomal trafficking in photoreceptors. | PMID: 28397838, OMIM #610036 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Retina | 15.2 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.0 | High expression |
| HeLa | 14.5 | Medium expression |
| SH-SY5Y | 16.2 | Medium expression |
| ARPE-19 | 20.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1492C>T (p.Arg498Trp) | Missense | Rare | Loss of function; disrupts CORVET complex assembly |
| c.1A>G (p.Met1Val) | Missense | Rare | Loss of function; abolishes translation initiation |
| c.1297G>A (p.Glu433Lys) | Missense | Rare | Loss of function; impairs protein stability |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations are loss-of-function, leading to reduced CORVET/HOPS complex activity and lysosomal dysfunction.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • endosome to lysosome transport | • autophagosome maturation |
| • protein localization to lysosome | • vesicle fusion |
| • endosomal transport |
Pathways
• Endosomal/Vacuolar trafficking (CORVET complex)
• Lysosomal trafficking (HOPS complex)
• Autophagy
Protein Summary
VPS33A is a 637-amino acid protein that belongs to the Sec1/Munc18 family. It is a core component of the class C VPS complex, which forms the CORVET (class C core vacuole/endosome tethering) and HOPS (homotypic fusion and vacuole protein sorting) complexes. These complexes mediate tethering and fusion of endosomes and lysosomes. VPS33A interacts with other class C VPS proteins (VPS11, VPS16, VPS18) and with Rab GTPases to regulate membrane trafficking. Loss of VPS33A function leads to lysosomal storage defects and impaired autophagy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS33A Knockout HEK293 Cell Line | EDJ-KQ15325 | Human | 65082 | Details Get a Quote |
| VPS33A Knockout HCT 116 Cell Line | EDJ-KQ47267 | Human | 65082 | Details Get a Quote |
| VPS33A Knockout HeLa Cell Line | EDJ-KQ47268 | Human | 65082 | Details Get a Quote |
| VPS33A Knockout A-549 Cell Line | EDJ-KQ65614 | Human | 65082 | Details Get a Quote |
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