Protein / target
Sodium/potassium-transporting ATPase subunit alpha-4
Protein at a glance
Biological role
P-type sodium:potassium-exchanging transporter
Strongest disease association
Non-syndromic male infertility due to sperm motility disorder
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Sperm-specific catalytic alpha subunit of the Na(+)/K(+)-ATPase responsible for ATP-dependent Na(+)/K(+) exchange across the plasma membrane.
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Sperm-specific catalytic alpha subunit of the Na(+)/K(+)-ATPase responsible for ATP-dependent Na(+)/K(+) exchange across the plasma membrane. Transports 3 Na(+) ions out of the cell and 2 K(+) ions into the cell for each ATP hydrolyze (PubMed:16861705). Plays an essential for sperm motility, capacitation, and male fertility by maintaining ionic gradients required for flagellar function and signaling (By similarity)
Subcellular location
Domains and Gene Ontology detail (27)Hide
Gene Ontology
- Ccell projection
- Cmembrane raft
- Cphotoreceptor cell cilium
- Cplasma membrane
- Crod photoreceptor outer segment
- Csodium:potassium-exchanging ATPase complex
- Csperm midpiece
- FATP binding
- FATP hydrolysis activity
- FATPase-coupled monoatomic cation transmembrane transporter activity
- Fkinase binding
- Fmetal ion binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Ion channel gating
- ·ATPase-coupled monoatomic cation transmembrane transporter activity
- ·potassium ion transmembrane transport
- ·sodium ion transmembrane transport
View underlying pathways (3)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
Broader indication categories (1)Hide
Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.
5 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
Sodium/potassium-transporting ATPase inhibitor
Indicated for Atrial Fibrillation, Heart Failure, Cardiovascular Diseases
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene ATP1A4
Gene-level evidence surfaced through the gene ATP1A4that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (3)Hide
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.
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Drug development
6 compounds recorded · 5 approved · 1 in clinical development
View all recorded compounds (6)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (9)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- Label change
Label change: DIGOXIN (ANDA040481)
- Trial status changed
A Phase 1, 3-part, Open-label Study to Evaluate the Effects of KarXT Administration on the Pharmacokinetics of Midazolam, Fexofenadine, and Digoxin in Healthy Adult Participants
- Trial status changed
A Phase 1 Study to Evaluate the Effect of Multiple Doses of ABBV-722 on the Pharmacokinetics of Cocktail Probe Substrates of CYP3A and Select Transporters in Healthy Adult Subjects
- New publicationDrug-Drug Interactions Between Glucagon-Like Peptide 1 Receptor Agonists and Oral Medications: A Systematic Review.
- Label change
Label change: DIGOXIN (ANDA040481)
- Label change
Label change: DIGOXIN (ANDA040481)
- Label change
Label change: DIGOXIN (ANDA040481)
- Label change
Label change: DIGOXIN (ANDA040481)
- Label change
Label change: DIGOXIN (ANDA040481)
- Label change
Label change: DIGOXIN (ANDA040481)
- Regulatory approval
Approval: DIGOXIN (ANDA040481)
- New publicationDual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.