ATP6V1D Gene - V-ATPase Subunit D
A subunit of the vacuolar ATPase complex involved in acidification and linked to renal and neurological disorders
Gene Information Card
| Symbol | ATP6V1D |
|---|---|
| Full Name | ATPase H+ Transporting V1 Subunit D |
| Gene Type | protein-coding |
| Chromosomal Location | 14q23.1 |
| NCBI Gene ID | 51382 ncbi.nlm.nih.gov/gene/51382 |
| Ensembl ID | ENSG00000100554 |
| UniProt ID | Q9Y5K8 |
| OMIM ID | 618120 |
| HGNC ID | 13527 |
| Aliases | VATD, VMA8, ATP6V1D1 |
Description
ATP6V1D encodes subunit D of the V1 domain of vacuolar ATPase (V-ATPase), a multi-subunit enzyme that mediates acidification of intracellular compartments. This subunit is essential for assembly and rotational catalysis of the V1 complex. V-ATPase acidifies lysosomes, endosomes, and secretory vesicles, playing critical roles in protein degradation, neurotransmitter uptake, and renal proton secretion.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Renal tubular acidosis (distal) with sensorineural deafness | Loss-of-function mutations impair V-ATPase proton transport in renal intercalated cells and inner ear, leading to metabolic acidosis and hearing loss | ClinVar, OMIM |
| Neurodevelopmental disorder with microcephaly and seizures | Biallelic missense variants disrupt V-ATPase assembly in neurons, affecting synaptic vesicle acidification and neurotransmission | ClinVar, OMIM |
| Cutis laxa (autosomal recessive type 2C) | Defective V-ATPase in Golgi and lysosomes impairs elastin processing and extracellular matrix homeostasis | UniProt, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 18.5 | High |
| Brain | 12.3 | Medium |
| Liver | 9.8 | Medium |
| Heart | 7.2 | Medium |
| Lung | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression in embryonic kidney cells |
| SH-SY5Y | 11.4 | Neuroblastoma line, relevant for neurological studies |
| HepG2 | 9.7 | Hepatocellular carcinoma line |
| A549 | 6.3 | Lung carcinoma line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.292C>T (p.Arg98Trp) | Missense | Rare | Loss of V-ATPase assembly; associated with neurodevelopmental disorder |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; associated with renal tubular acidosis |
| c.416G>A (p.Arg139Gln) | Missense | Rare | Impaired proton transport; reported in cutis laxa |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function variants (e.g., start loss, nonsense) cause severe renal and neurological phenotypes due to defective acidification.
Gain of Function (GOF)
No gain-of-function mutations reported for ATP6V1D.
Dominant Negative (DN)
Heterozygous missense variants may exert dominant-negative effects on V-ATPase assembly, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • vacuolar proton-transporting V-type ATPase (GO:0000221) | • ion transport (GO:0006811) |
| • ATP hydrolysis coupled proton transport (GO:0015991) | • proton-transporting ATPase activity (GO:0046961) |
| • lysosome (GO:0005764) |
Pathways
• V-ATPase-mediated acidification (Reactome: R-HSA-1222556)
• Lysosome (KEGG: hsa04142)
• Synaptic vesicle cycle (KEGG: hsa04721)
Protein Summary
Subunit D of the V1 domain of vacuolar ATPase. It is a 247-amino-acid protein (28 kDa) that forms part of the central stalk connecting the V1 catalytic head to the V0 proton channel. It is required for ATP-driven rotation and proton translocation. The protein is highly conserved across eukaryotes and is expressed in all tissues, with highest levels in kidney and brain.
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