ATP13A2
ATPase 13A2, a lysosomal cation transporter implicated in neurodegeneration and Parkinson disease
Gene Information Card
| Symbol | ATP13A2 |
|---|---|
| Full Name | ATPase 13A2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 23400 ncbi.nlm.nih.gov/gene/23400 |
| Ensembl ID | ENSG00000159363 |
| UniProt ID | Q9NQ11 |
| OMIM ID | 610513 |
| HGNC ID | 30213 |
| Aliases | PARK9, KRPPD, HSA9947 |
Description
ATP13A2 encodes a lysosomal P-type ATPase that transports cations (likely polyamines) across lysosomal membranes. It is essential for lysosomal homeostasis, autophagy, and mitochondrial function. Loss-of-function mutations cause Kufor-Rakeb syndrome (PARK9), an early-onset Parkinson disease with dementia, and are linked to sporadic Parkinson disease risk.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Kufor-Rakeb syndrome (PARK9) | Loss-of-function mutations impair lysosomal cation transport, leading to lysosomal dysfunction, impaired autophagy, and neurodegeneration. | OMIM #606693; ClinVar |
| Parkinson disease (early-onset, sporadic) | Heterozygous missense variants (e.g., p.A746T, p.G504R) reduce ATP13A2 activity, increasing alpha-synuclein aggregation and mitochondrial stress. | ClinVar; PMID: 22232232 |
| Neuronal ceroid lipofuscinosis (NCL) | Biallelic ATP13A2 mutations cause a severe NCL-like phenotype with lysosomal storage. | OMIM #204200; PMID: 22972638 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 6.2 | Medium |
| Brain (cerebellum) | 5.8 | Medium |
| Testis | 4.1 | Low |
| Kidney | 3.5 | Low |
| Liver | 2.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.5 | High expression |
| HEK293 (embryonic kidney) | 6.0 | Moderate expression |
| HeLa (cervical carcinoma) | 4.2 | Low expression |
| HepG2 (hepatocellular carcinoma) | 2.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1306+5G>A (splice site) | Splice site | Rare | Loss of function; causes Kufor-Rakeb syndrome |
| c.2237C>T (p.A746T) | Missense | 0.02% (gnomAD) | Reduced ATPase activity; risk factor for Parkinson disease |
| c.1510G>A (p.G504R) | Missense | 0.01% (gnomAD) | Impaired lysosomal localization; associated with early-onset Parkinson disease |
| c.1102C>T (p.R368*) | Nonsense | Rare | Premature stop; loss of function; Kufor-Rakeb syndrome |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, splice site) cause Kufor-Rakeb syndrome by abolishing lysosomal cation transport.
Gain of Function (GOF)
No evidence of gain-of-function mutations.
Dominant Negative (DN)
Heterozygous missense variants (e.g., p.A746T) may exert a dominant-negative effect by interfering with wild-type ATP13A2 oligomerization or trafficking.
View complete mutation data：
Gene Ontology (GO)
| • P-type calcium transporter activity (GO:0008559) | • lysosome (GO:0005764) |
| • autophagy (GO:0006914) | • integral component of membrane (GO:0016021) |
| • cation transport (GO:0006812) | • response to amino acid starvation (GO:0043200) |
Pathways
• Lysosomal cation homeostasis
• Autophagy – lysosome pathway
• Parkinson disease pathway (KEGG: hsa05012)
Protein Summary
ATP13A2 is a 1,180-amino-acid lysosomal transmembrane P-type ATPase that transports cations (likely polyamines) into the lysosomal lumen. It contains 10 transmembrane domains and a conserved ATP-binding domain. The protein is critical for lysosomal acidification, autophagic flux, and mitochondrial quality control. Mutations lead to lysosomal dysfunction, alpha-synuclein accumulation, and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP13A2 Knockout HEK293 Cell Line | EDJ-KQ12222 | Human | 23400 | Details Get a Quote |
| ATP13A2 Knockout HeLa Cell Line | EDJ-KQ18206 | Human | 23400 | Details Get a Quote |
| ATP13A2 Knockout HCT 116 Cell Line | EDJ-KQ40976 | Human | 23400 | Details Get a Quote |
| ATP13A2 Knockout A-549 Cell Line | EDJ-KQ39737 | Human | 23400 | Details Get a Quote |
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