ATP1A2
ATPase Na+/K+ Transporting Subunit Alpha 2
Gene Information Card
| Symbol | ATP1A2 |
|---|---|
| Full Name | ATPase Na+/K+ Transporting Subunit Alpha 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q23.2 |
| NCBI Gene ID | 477 ncbi.nlm.nih.gov/gene/477 |
| Ensembl ID | ENSG00000018625 |
| UniProt ID | P50993 |
| OMIM ID | 182340 |
| HGNC ID | 800 |
| Aliases | FHM2, MHP2, MGC169535 |
Description
The ATP1A2 gene encodes the alpha-2 catalytic subunit of the Na+/K+-ATPase, an integral membrane protein responsible for establishing and maintaining the electrochemical gradient of Na+ and K+ ions across the plasma membrane. This pump is essential for neuronal excitability, muscle contraction, and ion homeostasis. Mutations in ATP1A2 are associated with familial hemiplegic migraine type 2 (FHM2) and alternating hemiplegia of childhood (AHC).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial Hemiplegic Migraine 2 (FHM2) | Loss-of-function mutations reduce Na+/K+ pump activity, leading to impaired ion homeostasis and increased susceptibility to cortical spreading depression. | OMIM #182340; ClinVar |
| Alternating Hemiplegia of Childhood (AHC) | De novo missense mutations cause partial loss of pump function, resulting in episodic hemiplegia and neurological deficits. | OMIM #614820; ClinVar |
| Rapid-Onset Dystonia-Parkinsonism (RDP) | Rare missense variants impair pump activity, disrupting ion gradients in basal ganglia neurons. | OMIM #128235; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Medium |
| Skeletal Muscle | 6.7 | Low |
| Kidney | 4.2 | Low |
| Liver | 1.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.2 | Neuronal cell line |
| U-87 MG | 9.8 | Glioblastoma cell line |
| HEK 293 | 7.5 | Embryonic kidney cell line |
| HepG2 | 2.3 | Hepatocellular carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.857G>A (p.Arg286Gln) | Missense | <0.01% | Reduced pump activity; associated with FHM2 |
| c.2401C>T (p.Arg801*) | Nonsense | <0.01% | Truncated protein; loss of function; AHC |
| c.2735G>A (p.Arg912Gln) | Missense | <0.01% | Impaired ATP binding; FHM2 |
| c.1198C>T (p.Arg400Cys) | Missense | <0.01% | Decreased catalytic turnover; AHC |
Mutation functional classification
Loss of Function (LOF)
Most FHM2 and AHC mutations reduce Na+/K+ ATPase activity, impairing ion transport.
Gain of Function (GOF)
Not reported for ATP1A2.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg286Gln) exert dominant-negative effects by disrupting pump assembly.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • sodium:potassium-exchanging ATPase activity |
| • potassium ion transport | • sodium ion transport |
| • plasma membrane | • neuronal action potential propagation |
Pathways
• Na+/K+ ATPase ion transport
• Cardiac muscle contraction
• Neurotransmitter uptake and release
Protein Summary
The ATP1A2 protein (UniProt P50993) is a 1020-amino acid multi-pass membrane protein with 10 transmembrane domains. It catalyzes the ATP-dependent exchange of 3 Na+ out and 2 K+ into the cell. The alpha-2 isoform is predominantly expressed in brain, heart, and skeletal muscle. Mutations that impair its function lead to neuronal hyperexcitability and migraine or episodic movement disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP1A2 Knockout HEK293 Cell Line | EDJ-KQ1820 | Human | 477 | Details Get a Quote |
| ATP1A2 Knockout HeLa Cell Line | EDJ-KQ52679 | Human | 477 | Details Get a Quote |
| ATP1A2 Knockout A-549 Cell Line | EDJ-KQ61151 | Human | 477 | Details Get a Quote |
| ATP1A2 Knockout HCT 116 Cell Line | EDJ-KQ69639 | Human | 477 | Details Get a Quote |
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