VMA21
Function
Required for the assembly of the V0 complex of the vacuolar ATPase (V-ATPase) in the endoplasmic reticulum.
Involvement in disease
Myopathy, X-linked, with excessive autophagy
MEAX
A muscle disorder characterized by childhood early onset of a slowly progressive proximal limb muscle weakness (especially in legs) and elevation of serum creatine kinase, without evidence of cardiac, respiratory or central nervous system involvement. Histopathological analysis reveals diseased muscle fibers that are not necrotic, but show abnormal autophagic vacuolation as a manifestation of excessive autophagic activity in skeletal muscle cells.
None
The disease is caused by variants affecting the gene represented in this entry. VMA21 deficiency results in an increase of lysosomal pH from 4.7 to 5.2, which reduces lysosomal degradative ability and blocks autophagy. This reduces cellular free amino acids, which up-regulates the mTOR pathway and mTOR-dependent macroautophagy, resulting in proliferation of large and ineffective autolysosomes that engulf sections of cytoplasm, merge together, and vacuolate the cell.
Sequence Similarities
Belongs to the VMA21 family.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Endoplasmic reticulum-Golgi intermediate compartment membrane
- Multi-pass membrane protein
- Cytoplasmic vesicle
- COPII-coated vesicle membrane
- Multi-pass membrane protein
Alternative names
MEAX, XMEA, VMA21, Vacuolar ATPase assembly integral membrane protein VMA21, Myopathy with excessive autophagy protein