ATP6V1H Gene - V-type proton ATPase subunit H
Essential regulator of vacuolar acidification and cellular pH homeostasis
Gene Information Card
| Symbol | ATP6V1H |
|---|---|
| Full Name | ATPase H+ transporting V1 subunit H |
| Gene Type | protein-coding |
| Chromosomal Location | 8q11.23 |
| NCBI Gene ID | 51606 ncbi.nlm.nih.gov/gene/51606 |
| Ensembl ID | ENSG00000147224 |
| UniProt ID | Q9UI12 |
| OMIM ID | 607953 |
| HGNC ID | 18318 |
| Aliases | VMA13, CGI-11, V-ATPase subunit H, VPH1 |
Description
The ATP6V1H gene encodes the H subunit of the vacuolar (V-type) H+-ATPase (V-ATPase), a multi-subunit enzyme that mediates acidification of intracellular organelles such as lysosomes, endosomes, and secretory vesicles. The V1 domain is responsible for ATP hydrolysis, and subunit H is essential for coupling ATP hydrolysis to proton transport. ATP6V1H is ubiquitously expressed and plays critical roles in pH homeostasis, protein degradation, receptor recycling, and bone resorption. Mutations in this gene are associated with autosomal recessive osteopetrosis and distal renal tubular acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteopetrosis, autosomal recessive 2 (OPTB2) | Loss-of-function mutations impair osteoclast-mediated bone resorption due to defective lysosomal acidification | OMIM #259700; PMID: 28132693 |
| Distal renal tubular acidosis (dRTA) | Defective proton secretion in renal intercalated cells leads to metabolic acidosis | OMIM #607953; PMID: 28132693 |
| Cancer (multiple types) | Altered V-ATPase activity promotes tumor microenvironment acidification and metastasis | COSMIC; PMID: 25691885 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | High |
| Liver | 9.8 | Medium |
| Brain | 8.2 | Medium |
| Heart | 7.1 | Medium |
| Lung | 6.5 | Medium |
| Skeletal Muscle | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 11.0 | High expression |
| A549 | 9.5 | Medium expression |
| MCF7 | 7.8 | Medium expression |
| K562 | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.139C>T (p.Arg47*) | Nonsense | <0.01% | Loss of function; associated with osteopetrosis |
| c.437G>A (p.Arg146Gln) | Missense | <0.01% | Impaired V-ATPase assembly; dRTA |
| c.1120_1121del (p.Leu374fs) | Frameshift | <0.01% | Loss of function; osteopetrosis |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated or absent protein, causing osteopetrosis and dRTA.
Gain of Function (GOF)
Not reported in ATP6V1H.
Dominant Negative (DN)
Not reported in ATP6V1H.
View complete mutation data：
Gene Ontology (GO)
| • vacuolar proton-transporting V-type ATPase (GO:0000221) | • ATP binding (GO:0005524) |
| • ATP hydrolysis coupled proton transport (GO:0015991) | • proton-transporting ATPase activity (GO:0046961) |
| • lysosome (GO:0005764) |
Pathways
• KEGG: hsa00190 - Oxidative phosphorylation
• KEGG: hsa04142 - Lysosome
• Reactome: R-HSA-1222556 - Proton transport by V-type ATPase
Protein Summary
The V-type proton ATPase subunit H (UniProt Q9UI12) is a 483-amino acid protein (55 kDa) that forms part of the V1 peripheral catalytic domain. It acts as a stator that connects the V1 and V0 domains, regulating the rotational catalysis. The protein contains a N-terminal domain that binds the V1 A and B subunits and a C-terminal domain that interacts with the V0 a subunit. It is essential for efficient proton translocation and is highly conserved across eukaryotes.
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