ATP6V0C Gene - V-ATPase Subunit C
Essential component of vacuolar ATPase, involved in acidification and linked to neurodevelopmental disorders
Gene Information Card
| Symbol | ATP6V0C |
|---|---|
| Full Name | ATPase H+ Transporting V0 Subunit C |
| Gene Type | protein-coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 527 ncbi.nlm.nih.gov/gene/527 |
| Ensembl ID | ENSG00000103174 |
| UniProt ID | P27449 |
| OMIM ID | 108745 |
| HGNC ID | 866 |
| Aliases | ATP6C, VATP6C, VMA3, ATP6V0C1 |
Description
ATP6V0C encodes the C subunit of the vacuolar ATPase (V-ATPase) V0 domain, a multi-subunit enzyme that mediates acidification of intracellular organelles such as lysosomes, endosomes, and secretory vesicles. This proton pump is critical for cellular processes including protein degradation, receptor recycling, and neurotransmitter loading. Mutations in ATP6V0C are associated with autosomal recessive neurodevelopmental disorders and may contribute to lysosomal dysfunction.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia and brain abnormalities | Impaired V-ATPase function leads to defective organelle acidification, disrupting neuronal development and synaptic function | ClinVar, OMIM |
| Epileptic encephalopathy, early infantile | Loss of V-ATPase activity alters neuronal excitability and vesicle cycling | ClinVar |
| Lysosomal storage disorder-like phenotype | Reduced lysosomal acidification impairs hydrolase activity and substrate degradation | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Kidney | 10.2 | High |
| Liver | 8.7 | Medium |
| Heart | 7.3 | Medium |
| Lung | 6.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression |
| SH-SY5Y | 13.2 | Neuronal model |
| HepG2 | 9.8 | Hepatocyte model |
| A549 | 7.5 | Lung epithelial |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Loss of start codon, likely null allele |
| c.200T>C (p.Leu67Pro) | missense | <0.01% | Disrupts transmembrane domain, reduced V-ATPase assembly |
| c.346G>A (p.Gly116Arg) | missense | <0.01% | Impaired proton translocation |
| c.1_?del | deletion | <0.01% | Complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations are loss-of-function, leading to reduced V-ATPase activity and impaired organelle acidification.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • ATP hydrolysis coupled proton transport (GO:0015991) | • lysosome (GO:0005764) |
| • lysosomal membrane (GO:0005765) | • integral component of membrane (GO:0016021) |
| • proton-transporting ATPase activity (GO:0046961) |
Pathways
• V-ATPase-mediated acidification (Reactome: R-HSA-1222440)
• Lysosome (KEGG: hsa04142)
• Synaptic vesicle cycle (KEGG: hsa04721)
Protein Summary
ATP6V0C encodes the 16 kDa proteolipid subunit c of the V0 domain of vacuolar ATPase. This highly hydrophobic protein spans the membrane multiple times and forms part of the proton channel. It is essential for proton translocation across membranes, enabling acidification of intracellular compartments. The protein is ubiquitously expressed with highest levels in brain and kidney. Defects in ATP6V0C cause neurodevelopmental disorders due to disrupted pH homeostasis in neurons.
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