ATP1A4: Sodium/Potassium-Transporting ATPase Subunit Alpha 4
A testis-specific ion pump critical for sperm motility and male fertility
Gene Information Card
| Symbol | ATP1A4 |
|---|---|
| Full Name | ATPase Na+/K+ Transporting Subunit Alpha 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q23.2 |
| NCBI Gene ID | 480 ncbi.nlm.nih.gov/gene/480 |
| Ensembl ID | ENSG00000132681 |
| UniProt ID | Q13733 |
| OMIM ID | 607321 |
| HGNC ID | 802 |
| Aliases | ATP1A1L2, Na(+)/K(+) ATPase alpha 4 subunit |
Description
ATP1A4 encodes the alpha 4 catalytic subunit of the Na+/K+-ATPase, an integral membrane ion pump that maintains sodium and potassium gradients across the plasma membrane. This isoform is predominantly expressed in testis and is essential for sperm motility, capacitation, and male fertility. It is also expressed at low levels in other tissues such as heart and skeletal muscle.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility (asthenozoospermia) | Loss-of-function mutations impair Na+/K+ pump activity in sperm, reducing flagellar beat frequency and motility. | ClinVar, OMIM |
| Spermatogenic failure | Disrupted ion homeostasis in germ cells leads to defective sperm maturation. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 45.2 | High |
| Heart | 2.1 | Low |
| Skeletal muscle | 1.8 | Low |
| Kidney | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Spermatozoa | N/A | High expression in mature sperm flagella |
| NT2/D1 (testicular embryonal carcinoma) | 12.3 | Moderate expression |
| HeLa | 0.2 | Very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.245G>A (p.Arg82His) | Missense | <0.01% | Reduced pump activity, associated with asthenozoospermia |
| c.1124T>C (p.Leu375Pro) | Missense | <0.01% | Impaired protein folding and trafficking |
| c.1789C>T (p.Arg597*) | Nonsense | <0.01% | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations reduce or abolish Na+/K+ ATPase activity, leading to sperm motility defects.
Gain of Function (GOF)
Not reported for ATP1A4.
Dominant Negative (DN)
Not documented; likely recessive inheritance pattern.
View complete mutation data：
Gene Ontology (GO)
Pathways
• REACT:17015 – Ion transport by P-type ATPases
• REACT:17016 – Na+/K+ ATPase in ion homeostasis
Protein Summary
The ATP1A4 protein (alpha 4 subunit) is a 1030-amino acid transmembrane protein that forms the catalytic core of the Na+/K+-ATPase. It contains 10 transmembrane domains and ATP-binding sites. In sperm, it localizes to the flagellar principal piece and is required for maintaining the ionic environment necessary for flagellar beating. Its activity is regulated by phosphorylation and interactions with FXYD proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP1A4 Knockout HEK293 Cell Line | EDJ-KQ1138 | Human | 480 | Details Get a Quote |
| ATP1A4 Knockout HeLa Cell Line | EDJ-KQ52682 | Human | 480 | Details Get a Quote |
| ATP1A4 Knockout A-549 Cell Line | EDJ-KQ61153 | Human | 480 | Details Get a Quote |
| ATP1A4 Knockout HCT 116 Cell Line | EDJ-KQ69641 | Human | 480 | Details Get a Quote |
