ATP6V1B2 Gene - V-type proton ATPase subunit B, brain isoform
Essential regulator of lysosomal acidification and neuronal function
Gene Information Card
| Symbol | ATP6V1B2 |
|---|---|
| Full Name | ATPase H+ transporting V1 subunit B2 |
| Gene Type | protein-coding |
| Chromosomal Location | 8p21.3 |
| NCBI Gene ID | 526 ncbi.nlm.nih.gov/gene/526 |
| Ensembl ID | ENSG00000147416 |
| UniProt ID | P21281 |
| OMIM ID | 606939 |
| HGNC ID | 862 |
| Aliases | VATB, VPP3, ATP6B1B2, Vma2 |
Description
ATP6V1B2 encodes the B2 subunit of the vacuolar ATPase (V-ATPase) V1 domain, which is responsible for acidifying intracellular compartments such as lysosomes, endosomes, and synaptic vesicles. This subunit is predominantly expressed in the brain and is critical for neuronal pH homeostasis, neurotransmitter loading, and protein degradation. Mutations in ATP6V1B2 cause autosomal dominant deafness-onychodystrophy (DDOD) syndrome and are associated with developmental and epileptic encephalopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| DDOD syndrome (Deafness, Onychodystrophy, Dominant) | Dominant-negative or loss-of-function mutations impair V-ATPase assembly, reducing lysosomal acidification and causing sensorineural hearing loss and nail abnormalities. | ClinVar, OMIM #124480 |
| Developmental and epileptic encephalopathy 86 (DEE86) | Missense mutations disrupt proton transport, leading to impaired synaptic vesicle acidification and neuronal hyperexcitability. | ClinVar, OMIM #618663 |
| Autosomal dominant nonsyndromic hearing loss | Haploinsufficiency of ATP6V1B2 alters endocochlear potential and hair cell function. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 28.5 | High |
| Kidney | 12.3 | Medium |
| Testis | 9.8 | Medium |
| Liver | 4.2 | Low |
| Heart | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 32.1 | Neuronal model |
| HEK293 (embryonic kidney) | 18.7 | Common overexpression system |
| HeLa (cervical carcinoma) | 15.4 | Epithelial model |
| HepG2 (hepatocellular carcinoma) | 6.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1516C>T (p.Arg506*) | Nonsense | <0.01% | Premature stop; loss of function in DDOD |
| c.1390G>A (p.Glu464Lys) | Missense | <0.01% | Dominant-negative; DEE86 |
| c.1150C>T (p.Arg384Trp) | Missense | <0.01% | Impaired V-ATPase assembly; hearing loss |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations cause haploinsufficiency, leading to DDOD syndrome with hearing loss and nail dysplasia.
Gain of Function (GOF)
No gain-of-function mutations reported for ATP6V1B2.
Dominant Negative (DN)
Missense mutations (e.g., p.Glu464Lys) disrupt V1 domain assembly, impairing proton transport and causing severe epileptic encephalopathy.
View complete mutation data：
Gene Ontology (GO)
| • vacuolar proton-transporting V-type ATPase (GO:0000221) | • ATP hydrolysis coupled proton transport (GO:0015991) |
| • lysosome (GO:0005764) | • synaptic vesicle (GO:0008021) |
| • myelin sheath (GO:0043209) |
Pathways
• REACTOME: R-HSA-1222556 - Proton-coupled transport
• KEGG: hsa04721 - Synaptic vesicle cycle
• KEGG: hsa04142 - Lysosome
Protein Summary
The ATP6V1B2 protein (UniProt P21281) is a 511-amino-acid component of the V1 peripheral domain of vacuolar ATPase. It contains an ATP-binding site and is essential for catalytic activity. The brain isoform (B2) is highly expressed in neurons and glia. Structural studies show it forms a hexameric ring with other V1 subunits. Post-translational modifications include phosphorylation at Ser384, which regulates assembly. Defects in this protein disrupt acidification of lysosomes and synaptic vesicles, leading to neurodegeneration and sensory deficits.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID |
|---|
