ATP6V0D1: V-ATPase Subunit d1
A key component of the vacuolar ATPase proton pump, essential for organelle acidification and implicated in cancer and neurological disorders.
Gene Information Card
| Symbol | ATP6V0D1 |
|---|---|
| Full Name | ATPase H+ transporting V0 subunit d1 |
| Gene Type | protein-coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 9114 ncbi.nlm.nih.gov/gene/9114 |
| Ensembl ID | ENSG00000159720 |
| UniProt ID | P61421 |
| OMIM ID | 607464 |
| HGNC ID | 865 |
| Aliases | ATP6D, VMA6, VATX, V-ATPase 40 kDa subunit, V-ATPase d1 subunit |
Description
ATP6V0D1 encodes the d1 subunit 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 cellular pH homeostasis. Dysregulation of ATP6V0D1 is linked to cancer progression, neurodegenerative diseases, and lysosomal storage disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Altered V-ATPase activity promotes tumor cell invasion, metastasis, and drug resistance via extracellular acidification and lysosomal function modulation. | COSMIC; PubMed studies |
| Neurodegenerative disorders (e.g., Alzheimer's) | Impaired lysosomal acidification leads to accumulation of toxic proteins and defective autophagy. | ClinVar; OMIM |
| Lysosomal storage diseases | Reduced V-ATPase function disrupts lysosomal pH, impairing enzyme activity and substrate degradation. | OMIM; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Kidney | 10.8 | High |
| Liver | 8.2 | Medium |
| Heart | 7.1 | Medium |
| Lung | 6.5 | Medium |
| Pancreas | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical cancer cell line |
| HEK293 | 11.0 | Embryonic kidney cells |
| SH-SY5Y | 9.8 | Neuroblastoma cell line |
| MCF7 | 8.5 | Breast cancer cell line |
| A549 | 7.3 | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.124C>T (p.Arg42Cys) | Missense | <0.01% | Unknown; predicted to affect subunit interaction |
| c.287G>A (p.Arg96His) | Missense | <0.01% | Reported in ClinVar as variant of uncertain significance |
| c.445_447del (p.Lys149del) | In-frame deletion | <0.01% | Potential loss of function; associated with lysosomal dysfunction |
Mutation functional classification
Loss of Function (LOF)
Missense or deletion mutations that disrupt V-ATPase assembly or proton transport, leading to impaired organelle acidification.
Gain of Function (GOF)
Not well documented; overexpression in some cancers may enhance V-ATPase activity and tumor aggressiveness.
Dominant Negative (DN)
Mutations that produce a defective subunit capable of incorporating into the V-ATPase complex and inhibiting overall pump function.
View complete mutation data：
Gene Ontology (GO)
| • proton transmembrane transport (GO:0015992) | • ATP hydrolysis coupled proton transport (GO:0015991) |
| • vacuolar proton-transporting V-type ATPase complex (GO:0016471) | • lysosomal membrane (GO:0005765) |
| • endosome membrane (GO:0010008) |
Pathways
• V-ATPase mediated acidification (Reactome: R-HSA-917937)
• Lysosome (KEGG: hsa04142)
• Phagosome (KEGG: hsa04145)
• Synaptic vesicle cycle (KEGG: hsa04721)
Protein Summary
The ATP6V0D1 protein (UniProt P61421) is a 40 kDa component of the V0 domain of V-ATPase. It is essential for the assembly and proton translocation activity of the pump. The d1 subunit is ubiquitously expressed with high levels in brain and kidney. It interacts with other V0 subunits (a, c, c'', e) and the V1 catalytic domain. Post-translational modifications include phosphorylation, which may regulate complex assembly and activity.
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