ATP6V1G1: V-ATPase Subunit G1 – Key Regulator of Acidification and Cancer Metabolism
Comprehensive gene card for ATP6V1G1, including genomic annotation, expression, mutations, and disease associations.
Gene Information Card
| Symbol | ATP6V1G1 |
|---|---|
| Full Name | ATPase H+ Transporting V1 Subunit G1 |
| Gene Type | protein-coding |
| Chromosomal Location | 9q32 |
| NCBI Gene ID | 529 ncbi.nlm.nih.gov/gene/529 |
| Ensembl ID | ENSG00000136869 |
| UniProt ID | O75348 |
| OMIM ID | 606936 |
| HGNC ID | 862 |
| Aliases | Vma10, ATP6G, ATP6G1, V-ATPase G subunit 1 |
Description
ATP6V1G1 encodes the G1 subunit of the vacuolar (V-type) ATPase (V-ATPase), a multi-subunit enzyme that mediates acidification of intracellular organelles such as lysosomes, endosomes, and Golgi vesicles. The G subunit is part of the V1 peripheral domain responsible for ATP hydrolysis. Proper acidification is critical for protein degradation, receptor recycling, neurotransmitter uptake, and bone resorption. Dysregulation of V-ATPase activity is implicated in cancer, neurodegenerative disorders, and renal tubular acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Renal tubular acidosis (distal) | Loss-of-function mutations impair proton transport in renal intercalated cells, leading to defective urinary acidification. | ClinVar, OMIM |
| Cancer (multiple types) | Overexpression of ATP6V1G1 enhances extracellular acidification, promoting tumor invasion and metastasis. | COSMIC, NCBI PubMed |
| Neurodegenerative disorders | Altered V-ATPase activity disrupts lysosomal pH, contributing to protein aggregation in Alzheimer and Parkinson diseases. | NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Kidney | 18.3 | Medium |
| Liver | 8.9 | Low |
| Lung | 15.2 | Medium |
| Breast | 10.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.7 | Cervical cancer line |
| A549 | 16.2 | Lung adenocarcinoma |
| MCF7 | 11.3 | Breast cancer line |
| HEK293 | 13.8 | Embryonic kidney |
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 loss of function |
| c.124G>A (p.Glu42Lys) | missense | 0.02% | Unknown significance |
| c.346C>T (p.Arg116Trp) | missense | 0.01% | Possibly damaging (PolyPhen-2) |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the start codon or critical residues impair V-ATPase assembly and proton transport, leading to distal renal tubular acidosis.
Gain of Function (GOF)
Not well documented; overexpression in tumors may confer a gain-of-function by increasing acid secretion.
Dominant Negative (DN)
Not reported for ATP6V1G1.
View complete mutation data：
Gene Ontology (GO)
| • ATP hydrolysis coupled proton transport (GO:0015991) | • vacuolar proton-transporting V-type ATPase (GO:0000220) |
| • lysosome (GO:0005764) | • plasma membrane (GO:0005886) |
Pathways
• REAC:R-HSA-917937 – Ion transport by P-type ATPases
• REAC:R-HSA-983712 – Proton-coupled transport
Protein Summary
The ATP6V1G1 protein (UniProt O75348) is a 118-amino acid component of the V1 domain of V-ATPase. It is essential for coupling ATP hydrolysis to proton translocation. The protein is localized to the membrane of intracellular vesicles and, in some cell types, to the plasma membrane. Its expression is ubiquitous but enriched in kidney and brain.
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