ATP6V0A4: V-type proton ATPase subunit a4
A key regulator of renal acid-base homeostasis and auditory function
Gene Information Card
| Symbol | ATP6V0A4 |
|---|---|
| Full Name | ATPase H+ transporting V0 subunit a4 |
| Gene Type | protein-coding |
| Chromosomal Location | 7q34 |
| NCBI Gene ID | 50617 ncbi.nlm.nih.gov/gene/50617 |
| Ensembl ID | ENSG00000105974 |
| UniProt ID | Q9HBG4 |
| OMIM ID | 605239 |
| HGNC ID | 866 |
| Aliases | ATP6N1B, VPH1, a4, VPP2 |
Description
ATP6V0A4 encodes the a4 subunit of the vacuolar ATPase (V-ATPase) V0 domain, a proton pump that acidifies intracellular compartments and transports protons across plasma membranes. This subunit is specifically expressed in kidney intercalated cells and inner ear, where it is essential for urine acidification and endolymph pH regulation. Mutations cause autosomal recessive distal renal tubular acidosis (dRTA) with sensorineural deafness.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Distal renal tubular acidosis (dRTA) with deafness | Loss-of-function mutations impair proton secretion in renal collecting duct, leading to metabolic acidosis and hearing loss due to disrupted endolymph pH | ClinVar, OMIM |
| Osteopetrosis (rare) | Impaired osteoclast acidification due to V-ATPase dysfunction reduces bone resorption | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | High |
| Inner ear (cochlea) | 8.2 | Medium |
| Testis | 4.1 | Low |
| Brain | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression in renal cell line |
| MCF7 | 3.5 | Low expression |
| HepG2 | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.115C>T (p.Arg39*) | Nonsense | Rare | Loss of function – premature stop codon |
| c.1546G>A (p.Gly516Arg) | Missense | Rare | Impaired proton transport |
| c.2299C>T (p.Arg767Trp) | Missense | Rare | Reduced V-ATPase assembly |
Mutation functional classification
Loss of Function (LOF)
Most ATP6V0A4 mutations are loss-of-function, leading to defective proton pumping in renal intercalated cells and inner ear.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • ATP hydrolysis coupled proton transport (GO:0015991) | • regulation of pH (GO:0006885) |
| • ion transmembrane transport (GO:0034220) | • apical plasma membrane (GO:0016324) |
| • lysosome (GO:0005764) |
Pathways
• V-ATPase-mediated acidification (Reactome: R-HSA-1222556)
• Renal tubular transport (KEGG: hsa04964)
Protein Summary
The V-type proton ATPase subunit a4 (UniProt Q9HBG4) is a 840-amino acid multi-pass membrane protein that forms part of the V0 domain of V-ATPase. It is essential for proton translocation across membranes, particularly in kidney intercalated cells and inner ear epithelial cells. The a4 isoform confers tissue-specific targeting and regulation of the pump.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP6V0A4 Knockout HEK293 Cell Line | EDJ-KQ1902 | Human | 50617 | Details Get a Quote |
| ATP6V0A4 Knockout HeLa Cell Line | EDJ-KQ20510 | Human | 50617 | Details Get a Quote |
| ATP6V0A4 Knockout A-549 Cell Line | EDJ-KQ64665 | Human | 50617 | Details Get a Quote |
| ATP6V0A4 Knockout HCT 116 Cell Line | EDJ-KQ73114 | Human | 50617 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
