VMA21: Vacuolar ATPase Assembly Factor and Key Regulator of Lysosomal Acidification
Essential chaperone for V-ATPase assembly; mutations cause autophagic vacuolar myopathy
Gene Information Card
| Symbol | VMA21 |
|---|---|
| Full Name | Vacuolar ATPase Assembly Factor 21 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq28 |
| NCBI Gene ID | 203547 ncbi.nlm.nih.gov/gene/203547 |
| Ensembl ID | ENSG00000101981 |
| UniProt ID | Q3ZAQ7 |
| OMIM ID | 300669 |
| HGNC ID | 22082 |
| Aliases | MGC2408, XMEA |
Description
VMA21 encodes a chaperone protein essential for the assembly of the V0 domain of the vacuolar ATPase (V-ATPase), the proton pump responsible for acidifying lysosomes and other intracellular organelles. Proper V-ATPase function is critical for autophagy, endocytosis, and protein degradation. Loss-of-function mutations in VMA21 cause X-linked myopathy with excessive autophagy (XMEA), characterized by impaired lysosomal acidification and accumulation of autophagic vacuoles in muscle tissue.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked myopathy with excessive autophagy (XMEA) | Loss-of-function mutations in VMA21 impair V-ATPase assembly, leading to defective lysosomal acidification, accumulation of autophagic vacuoles, and muscle fiber degeneration. | ClinVar, OMIM #310440 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | Medium |
| Heart | 8.2 | Low |
| Brain | 6.1 | Low |
| Liver | 5.3 | Low |
| Kidney | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | Cervical carcinoma; moderate expression |
| HepG2 | 10.1 | Hepatocellular carcinoma |
| K562 | 7.8 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.164-2A>G | Splice acceptor | Rare (found in XMEA families) | Skipping of exon 3, frameshift, loss of function |
| c.97C>T (p.Arg33*) | Nonsense | Rare | Premature stop, truncated protein, loss of function |
| c.1A>G (p.Met1?) | Start loss | Rare | No translation initiation, complete loss of function |
Mutation functional classification
Loss of Function (LOF)
All reported pathogenic VMA21 mutations are loss-of-function, leading to impaired V-ATPase assembly and lysosomal acidification defects.
Gain of Function (GOF)
No gain-of-function mutations have been described for VMA21.
Dominant Negative (DN)
No dominant-negative mutations reported; X-linked recessive inheritance pattern.
View complete mutation data：
Gene Ontology (GO)
| • vacuolar proton-transporting V-type ATPase (GO:0000221) | • intracellular protein transport (GO:0006886) |
| • vacuolar transport (GO:0007034) | • ATP hydrolysis coupled proton transport (GO:0015991) |
| • proton-transporting two-sector ATPase complex (GO:0033178) | • clathrin-coated endocytic vesicle (GO:0045334) |
Pathways
• V-ATPase assembly and function (Reactome: R-HSA-5250913)
• Autophagy (KEGG: hsa04140)
• Lysosome (KEGG: hsa04142)
Protein Summary
VMA21 is a small, highly conserved chaperone protein (approximately 10 kDa) localized to the endoplasmic reticulum and Golgi apparatus. It facilitates the assembly of the V0 proton channel of the V-ATPase complex by mediating the interaction between V0 subunits and the ER membrane. Without VMA21, V-ATPase fails to assemble, resulting in defective lysosomal acidification and impaired autophagy. The protein is ubiquitously expressed, with highest levels in skeletal muscle, consistent with the tissue-specific phenotype of XMEA.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VMA21 Knockout HEK293 Cell Line | EDJ-KQ5574 | Human | 203547 | Details Get a Quote |
| VMA21 Knockout A-549 Cell Line | EDJ-KQ28841 | Human | 203547 | Details Get a Quote |
| VMA21 Knockout HCT 116 Cell Line | EDJ-KQ28842 | Human | 203547 | Details Get a Quote |
| VMA21 Knockout HeLa Cell Line | EDJ-KQ28843 | Human | 203547 | Details Get a Quote |
