ATP6V0A1: A Key Subunit of the Vacuolar ATPase
Essential for acidification of intracellular organelles and implicated in neurological disorders and cancer
Gene Information Card
| Symbol | ATP6V0A1 |
|---|---|
| Full Name | ATPase H+ transporting V0 subunit a1 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 535 ncbi.nlm.nih.gov/gene/535 |
| Ensembl ID | ENSG00000033627 |
| UniProt ID | Q93050 |
| OMIM ID | 192130 |
| HGNC ID | 865 |
| Aliases | VPP1, Vph1, ATP6N1, ATP6N1A, a1, V-ATPase a1 subunit |
Description
The ATP6V0A1 gene encodes the a1 subunit (V0 domain) of the vacuolar ATPase (V-ATPase), a multi-subunit enzyme that acidifies intracellular organelles such as lysosomes, endosomes, and secretory vesicles. This proton pump is critical for protein degradation, receptor recycling, neurotransmitter loading, and autophagy. Mutations in ATP6V0A1 are associated with autosomal recessive cutis laxa type II and neurodevelopmental disorders. Altered expression is observed in various cancers, influencing tumor progression and drug resistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cutis laxa, autosomal recessive, type IIA | Loss-of-function mutations impair lysosomal acidification, leading to defective elastin metabolism and connective tissue abnormalities. | OMIM #219200 |
| Neurodevelopmental disorder with hypotonia and brain abnormalities | Biallelic missense variants disrupt V-ATPase assembly and endolysosomal pH regulation, causing neuronal dysfunction. | ClinVar |
| Epileptic encephalopathy, early infantile | De novo dominant-negative mutations affect proton transport, resulting in severe seizures and developmental delay. | ClinVar |
| Cancer (multiple types) | Overexpression in breast, lung, and pancreatic cancers promotes acidification of tumor microenvironment, invasion, and chemoresistance. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 27.8 | High |
| Kidney | 19.2 | Medium |
| Liver | 15.4 | Medium |
| Heart | 12.1 | Medium |
| Lung | 10.5 | Medium |
| Pancreas | 8.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 32.5 | High expression |
| HeLa | 28.1 | High expression |
| A549 | 22.4 | Medium expression |
| MCF7 | 18.7 | Medium expression |
| K562 | 9.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1546C>T (p.Arg516Trp) | Missense | Rare | Loss of function; impairs V-ATPase assembly |
| c.2023G>A (p.Gly675Arg) | Missense | Rare | Dominant-negative; disrupts proton translocation |
| c.1234_1236del (p.Lys412del) | In-frame deletion | Rare | Reduced protein stability and pump activity |
| c.88C>T (p.Arg30*) | Nonsense | Very rare | Premature truncation; complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Biallelic missense or nonsense variants that reduce or abolish V-ATPase activity, leading to cutis laxa and neurodevelopmental disorders.
Gain of Function (GOF)
Not well documented; overexpression in cancer may confer a gain-of-function by enhancing acidification and invasion.
Dominant Negative (DN)
De novo missense mutations (e.g., p.Gly675Arg) that interfere with proton transport despite wild-type allele, causing severe epileptic encephalopathy.
View complete mutation data：
Gene Ontology (GO)
| • ATP hydrolysis coupled proton transport (GO:0015991) | • lysosome (GO:0005764) |
| • lysosomal membrane (GO:0005765) | • proton-transporting V-type ATPase (GO:0033179) |
| • proton-transporting ATPase activity (GO:0046961) |
Pathways
• V-ATPase-mediated acidification (Reactome: R-HSA-1222556)
• Lysosome (KEGG: hsa04142)
• Autophagy (KEGG: hsa04140)
• Endocytosis (KEGG: hsa04144)
Protein Summary
The ATP6V0A1 protein (a1 subunit) is a 840-amino acid integral membrane component of the V0 domain of V-ATPase. It contains a large cytoplasmic N-terminal domain and a C-terminal domain with multiple transmembrane helices that form the proton channel. The a1 subunit is essential for targeting V-ATPase to specific organelles and for regulating proton translocation. It interacts with other V0 subunits (c, c', c'', d, e) and with the V1 catalytic domain. Post-translational modifications include glycosylation and phosphorylation, which modulate its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP6V0A1 Knockout HEK293 Cell Line | EDJ-KQ4113 | Human | 535 | Details Get a Quote |
| ATP6V0A1 Knockout HCT 116 Cell Line | EDJ-KQ25176 | Human | 535 | Details Get a Quote |
| ATP6V0A1 Knockout A-549 Cell Line | EDJ-KQ26509 | Human | 535 | Details Get a Quote |
| ATP6V0A1 Knockout HeLa Cell Line | EDJ-KQ26510 | Human | 535 | Details Get a Quote |
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