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Protein / target

Sodium/potassium-transporting ATPase subunit alpha-4

Encoded byATP1A4Q13733Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

P-type sodium:potassium-exchanging transporter

Strongest disease association

Non-syndromic male infertility due to sperm motility disorder

Via encoding gene ATP1A4 · Animal model evidence · score 0.10

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

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.

View complete UniProt function annotation

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

Cell membrane
Domains and Gene Ontology detail (27)

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

1029 aa · 114 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Ion channel gatingGO
View supporting evidence

Ion channel gating

  • ·ATPase-coupled monoatomic cation transmembrane transporter activity
  • ·potassium ion transmembrane transport
  • ·sodium ion transmembrane transport
View underlying pathways (3)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

FXYD2ATP1B1ATP1B3ATP1B2ATP1B4ATP1A3ATP1A2MAPK1MAPK3FXYD1ATP1A4

10 strongest partners — larger node and heavier line mean higher confidence

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

1 medicine · 3 areas

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.

Atrial Fibrillation1 medicine
Heart Failure1 medicine
Broader indication categories (1)
Cardiovascular Diseases1 medicine

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

1

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.

Digoxin
ApprovedInhibitor

Sodium/potassium-transporting ATPase inhibitor

Indicated for Atrial Fibrillation, Heart Failure, Cardiovascular Diseases

Acts on a complex — shared with ATP1A1, ATP1B2, ATP1B1 +4 more · 1 of 8 recorded protein targets — broad pharmacology

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

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.

Non-syndromic male infertility due to sperm motility disorder
0.34Preliminary

Animal model evidence dominant · Open Targets 0.10 · no direct causal or clinical evidence

Spermatogenic failure
0.32Preliminary

Animal model evidence dominant · Open Targets 0.10 · no direct causal or clinical evidence

Breast Neoplasms
0.12Preliminary

Clinical evidence dominant · Open Targets 0.10

View evidence synthesis (3)
Non-syndromic male infertility due to sperm motility disorderPreliminary
0.34
agreement 0.110.57
Animal model100%

Open Targets aggregate 0.10 · 1 independent evidence family · no direct causal or clinical evidence

Spermatogenic failurePreliminary
0.32
agreement 0.090.55
Animal model100%

Open Targets aggregate 0.10 · 1 independent evidence family · no direct causal or clinical evidence

Breast NeoplasmsPreliminary
0.12
agreement 0.000.28
Clinical96%Literature4%

Open Targets aggregate 0.10 · 2 independent evidence families

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.

Show all associations
Non-syndromic male infertility due to sperm motility disorder0.10
Spermatogenic failure0.10
Breast Neoplasms0.10

Drug development

6 compounds recorded · 5 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (6)
LANATOSIDE CApproval
DIGITOXINApproval
ACETYLDIGITOXINApproval
DIGOXINApproval
ISTAROXIMEPhase 2 3
DESLANOSIDEApproval

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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

atrioventricular blockLynch et al. (2017)decreased heart rateLynch et al. (2017)increased urine excretionLynch et al. (2017)vomitingLynch et al. (2017)increased cardiac contractilityLynch et al. (2017)cardiac arrhythmiaLynch et al. (2017)increased urinary sodium excretionLynch et al. (2017)ventricular fibrillationLynch et al. (2017)

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

30

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)

RECRUITING · via Digoxin · NCT06588699

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

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.

  1. Label change2026-08-10

    Label change: DIGOXIN (ANDA040481)

    fda · regulatory · fda · via Digoxin

  2. Trial status changed2026-07-22

    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

    Status changed to Completed · ClinicalTrials.gov · via Digoxin

  3. Trial status changed2026-07-20

    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

    Status changed to Active, not recruiting · ClinicalTrials.gov · via Digoxin

  4. New publication2024-01-25
    Drug-Drug Interactions Between Glucagon-Like Peptide 1 Receptor Agonists and Oral Medications: A Systematic Review.

    Drug safety · 2024 · 37 citations · Europe PMC · via Digoxin

  5. Label change2020-07-16

    Label change: DIGOXIN (ANDA040481)

    fda · regulatory · fda · via Digoxin

  6. Label change2020-07-16

    Label change: DIGOXIN (ANDA040481)

    fda · regulatory · fda · via Digoxin

  7. Label change2016-11-02

    Label change: DIGOXIN (ANDA040481)

    fda · regulatory · fda · via Digoxin

  8. Label change2016-11-02

    Label change: DIGOXIN (ANDA040481)

    fda · regulatory · fda · via Digoxin

  9. Label change2012-04-27

    Label change: DIGOXIN (ANDA040481)

    fda · regulatory · fda · via Digoxin

  10. Label change2010-05-18

    Label change: DIGOXIN (ANDA040481)

    fda · regulatory · fda · via Digoxin

  11. Regulatory approval2003-08-21

    Approval: DIGOXIN (ANDA040481)

    fda · regulatory · fda · via Digoxin

  12. New publication2002-12-01
    Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial.

    JAMA · 2002 · 1,354 citations · Europe PMC · via Digoxin

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.