VAC14: A Key Regulator of PI(3,5)P2 Synthesis and Endolysosomal Function
Essential component of the PIKfyve complex; mutations cause neurodegeneration and immune disorders.
Gene Information Card
| Symbol | VAC14 |
|---|---|
| Full Name | VAC14 component of PIKfyve complex |
| Gene Type | Protein coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 55697 ncbi.nlm.nih.gov/gene/55697 |
| Ensembl ID | ENSG00000103035 |
| UniProt ID | Q08AM6 |
| OMIM ID | 608632 |
| HGNC ID | 25507 |
| Aliases | TAX1BP2, FLJ11029, Vac14 |
Description
VAC14 encodes a scaffold protein that forms a complex with PIKfyve (PIP5K3) and FIG4 (SAC3) to regulate the synthesis of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), a signaling lipid critical for endolysosomal trafficking, autophagy, and membrane homeostasis. Loss-of-function mutations cause progressive neurodegeneration, immune dysregulation, and lysosomal storage defects.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| VAC14-related neurodegeneration (progressive cerebellar atrophy, spasticity, dystonia) | Impaired PI(3,5)P2 synthesis leads to enlarged lysosomes, defective autophagy, and neuronal cell death. | ClinVar, OMIM #608632 |
| Striatonigral degeneration, childhood-onset | Biallelic VAC14 mutations disrupt endolysosomal trafficking in basal ganglia neurons. | OMIM #617457 |
| Immunodeficiency with recurrent infections | VAC14 deficiency impairs immune cell vesicle trafficking and cytokine release. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 7.9 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.0 | High expression |
| SH-SY5Y | 11.5 | Neuronal model |
| HeLa | 9.8 | Moderate expression |
| Jurkat | 7.2 | T-cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1622G>A (p.Arg541His) | Missense | Rare | Loss of PIKfyve complex stability; reduced PI(3,5)P2 levels |
| c.2113C>T (p.Arg705*) | Nonsense | Rare | Premature truncation; complete loss of function |
| c.1A>G (p.Met1?) | Start loss | Rare | No protein translation |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, start loss) cause severe early-onset neurodegeneration and immunodeficiency.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg541His) may exert dominant-negative effects by disrupting PIKfyve complex assembly.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidylinositol-3 | • 5-bisphosphate biosynthetic process |
| • endosome to lysosome transport | • autophagy |
| • PIKfyve complex | • cytosol |
| • lysosome |
Pathways
• PI(3
• 5)P2 synthesis (PIKfyve-FIG4-VAC14)
• Endolysosomal trafficking
• Autophagy-lysosome pathway
Protein Summary
VAC14 is a 782-amino-acid scaffold protein that binds PIKfyve and FIG4 to form the PIKfyve complex. It is essential for the production of PI(3,5)P2, which regulates vesicle fission, lysosomal acidification, and autophagy. The protein is ubiquitously expressed, with highest levels in brain and testis. Mutations lead to lysosomal enlargement, impaired autophagy, and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VAC14 Knockout HEK293 Cell Line | EDJ-KQ16088 | Human | 55697 | Details Get a Quote |
| VAC14 Knockout HeLa Cell Line | EDJ-KQ46005 | Human | 55697 | Details Get a Quote |
| VAC14 Knockout A-549 Cell Line | EDJ-KQ47232 | Human | 55697 | Details Get a Quote |
| VAC14 Knockout HCT 116 Cell Line | EDJ-KQ47233 | Human | 55697 | Details Get a Quote |
