Protein / target

Sodium/potassium-transporting ATPase subunit alpha-4

ATP1A4Q13733Homo sapiensSwiss-Prot
UniProt: Q13733Ensembl: ENSG00000132681HGNC: HGNC:14073NCBI Gene: 480
Clinically validated
Therapeutic maturity
5
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

P-type sodium:potassium-exchanging transporter activity

Strongest disease association

congestive heart failure

Clinical evidence · score 0.60

Therapeutic maturity

Clinically validated target

5 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

5 approved · 1 in clinical development

30 linked trials

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

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)
Ion homeostasis
Ion transport by P-type ATPases
Potential therapeutics for SARS

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.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Digoxin
ApprovedInhibitor

Sodium/potassium-transporting ATPase inhibitor

Appears in clinical studies involving congestive heart failure, atrial fibrillation, heart failure, cardiovascular disorder

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

congestive heart failure0.99

Clinical · overall 0.60

atrial fibrillation0.98

Clinical · overall 0.59

heart failure0.95

Clinical · overall 0.58

cardiovascular disorder0.91

Clinical · overall 0.55

Arrhythmia0.83

Clinical · overall 0.50

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

Supraventricular tachycardia0.32

Clinical

atrial flutter0.26

Clinical

non-syndromic male infertility due to sperm motility disorder0.10

Animal model

spermatogenic failure0.10

Animal model

breast cancer0.10

Clinical

Show all associations
congestive heart failure0.60
atrial fibrillation0.59
heart failure0.58
cardiovascular disorder0.55
Arrhythmia0.50
Supraventricular tachycardia0.32
atrial flutter0.26
non-syndromic male infertility due to sperm motility disorder0.10
spermatogenic failure0.10
breast cancer0.10

Open Targets ranks 126 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 6 total

LANATOSIDE CApproval

cardiovascular disorder

DIGITOXINApproval

cardiovascular disorder · Arrhythmia · heart failure

ACETYLDIGITOXINApproval

cardiovascular disorder · congestive heart failure

DIGOXINApproval

congestive heart failure · atrial fibrillation · heart failure

ISTAROXIMEPhase 2 3

heart disorder · heart failure · heart failure

DESLANOSIDEApproval

cardiovascular disorder · Arrhythmia · heart failure

Tractability

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

Safety liabilities

atrioventricular blockdecreased heart rateincreased urine excretionvomitingincreased cardiac contractilitycardiac arrhythmiaincreased urinary sodium excretionventricular fibrillation

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.

Relative Bioavailability of Digoxin After Co-administration of Multiple Oral Doses of Digoxin (0.25 mg qd) and Multiple Oral Doses of BI 1356 (5 mg qd) Compared to the Bioavailability of Multiple Oral Doses of Digoxin (0.25 mg qd) Alone in Healthy Male and Female Volunteers (an Open-label, Randomized, Two-way Crossover Clinical Phase I Study)PHASE1

COMPLETED · via Digoxin · NCT02183402

Two Way Crossover Oral Drug-drug Interaction Study of Spironolactone (Perpetrator) and Digoxin (Substrate Drug) in Healthy Adult Human Subjects Under Fasting ConditionPHASE1

COMPLETED · via Digoxin · NCT03909529

A Phase III Study of AL3818 (Anlotinib, Catequentinib) Hydrochloride Monotherapy in Subjects With Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial SarcomaPHASE3

RECRUITING · via Digoxin · NCT03016819

A Single Arm, Open and Fixed Sequence Study to Investigate the Pharmacokinetic Effects of Apatinib Mesylate on Transporter Pgp Substrate Digoxin in Advanced Solid Tumor SubjectsPHASE1

COMPLETED · via Digoxin · NCT04322552

An Open-Label Study of the Effect of Bardoxolone Methyl on the Single Dose Pharmacokinetics of Digoxin and Rosuvastatin in Healthy VolunteersPHASE1

COMPLETED · via Digoxin · NCT01598363

A Phase 1 Study to Evaluate the Effect of BCX7353 on the Single Dose Pharmacokinetics of the P-gp Substrate Digoxin and the BCRP Substrate Rosuvastatin and the Effect of the P-gp Inhibitor Cyclosporine on the Single Dose Pharmacokinetics of BCX7353PHASE1

COMPLETED · via Digoxin · NCT03136237

Show remaining trials (24)
A Single-center, Open-label, Fixed-sequence, Study Evaluating the Two-way Drug-drug Interaction Between JNJ-70033093 and Digoxin in Healthy SubjectsPHASE1

COMPLETED · via Digoxin · NCT04206488

A Phase 1, Open Label, Fixed Sequence Study to Evaluate the Effect of ECC5004 on the Single Dose Pharmacokinetics of Atorvastatin, Rosuvastatin, Digoxin and Midazolam in Healthy ParticipantsPHASE1

COMPLETED · via Digoxin · NCT06293742

A Phase 1, Open-label, Randomized, Two-period, Two-treatment, Crossover Study to Evaluate the Effect of Bexagliflozin on the Pharmacokinetics of Digoxin in Healthy SubjectsPHASE1

COMPLETED · via Digoxin · NCT03197324

A Phase I, Open-Label, Two-Period, One-Sequence, Crossover Study in Healthy Subjects to Evaluate the Clinical Drug-Drug Interaction of Divarasib With Probe Substrates of P-Glycoprotein (Digoxin) and Breast Cancer Resistance Protein (Rosuvastatin)PHASE1

COMPLETED · via Digoxin · NCT06677957

A Phase I, Open-label, Single-center Study to Assess the Pharmacokinetics of Digoxin in Healthy Subjects When Administered Alone and in Combination With a Single Dose of Vandetanib (CAPRELSA) 300 mgPHASE1

COMPLETED · via Digoxin · NCT01561781

An Open-label, Healthy Subject, Two-part Study to Assess the Effect of Verapamil on Systemic Exposure of EP395 (Part A), and to Assess the Effect of EP395 on Systemic Exposure of Midazolam and Digoxin (Part B)PHASE1

COMPLETED · via Digoxin · NCT06118684

A Phase I, Fixed-sequence, Open-label Study to Assess the Effects of Savolitinib on the Pharmacokinetics of Substrates of Human Transporters Digoxin (P-gp), Rosuvastatin (OATP1B1/3), Metformin (OCT2, MATE1/2K), and Furosemide (OAT1/3) in Healthy Male SubjectsPHASE1

COMPLETED · via Digoxin · NCT05768360

A Four-part, Single-center, Open-label, Phase I Clinical Study to Evaluate the Drug-drug Interactions (DDIs) Between GP681 and Rosuvastatin/Digoxin/Itraconazole/Oseltamivir in Chinese Healthy VolunteersPHASE1

COMPLETED · via Digoxin · NCT05789342

A Phase I, Open-Label, Single-Arm, Fixed-Sequence Study to Evaluate the Effect of Repeated Administration of HDM1002 on the Pharmacokinetics of Repaglinide, Atorvastatin, Digoxin and Rosuvastatin in Healthy and Overweight Adult Chinese SubjectsPHASE1

NOT_YET_RECRUITING · via Digoxin · NCT06601517

A Phase 1, Drug-Drug Interaction Study to Evaluate the Safety, Tolerability, and the Induction Potential of TBAJ-876 on CYP3A4 and P-glycoprotein and the Inhibition Potential of TBAJ-876 on P-glycoprotein in Healthy Adult SubjectsPHASE1

COMPLETED · via Digoxin · NCT05526911

A Three-part, Single-center, Open-label, Phase I Clinical Study to Evaluate the Drug-drug Interactions (DDIs) Between DBPR108 and Warfarin Sodium/Digoxin/Probenecid in Healthy SubjectsPHASE1

COMPLETED · via Digoxin · NCT05045313

Clinical Trial of Oral Digoxin In NASH (CODIN)PHASE2

RECRUITING · via Digoxin · NCT06588699

A Phase 1, Single-center, Open-label, Sequential Study to Evaluate the Drug-drug Interaction Potential of BMS-986196 in Healthy ParticipantsPHASE1

COMPLETED · via Digoxin · NCT05852769

Investigation of Mutual Pharmacokinetic Interactions of Digoxin, Furosemide, Metformin, and Rosuvastatin Given All Together as a Probe Cocktail for Key Drug Transporters (an Open-label, Randomised, Single-dose, Five-way Crossover Study)PHASE1

COMPLETED · via Digoxin · NCT02854527

A Two-way Cross-over, Placebo-controlled Interaction Trial in Two Parts (in Healthy Subjects), Studying Liraglutide's Potential Influence on the Absorption Pharmacokinetics of Lisinopril, Atorvastatin, Griseofulvin and Digoxin, and Liraglutide's Potential Influence on Intragastric pHPHASE1

COMPLETED · via Digoxin · NCT01518166

A Drug-Drug Interaction Study to Assess the Effect of Orforglipron on the Pharmacokinetics of Digoxin, Simvastatin, Rosuvastatin, Acetaminophen, and Midazolam in Healthy Overweight and Obese ParticipantsPHASE1

COMPLETED · via Digoxin · NCT06186622

A Phase III Clinical Trial to Compare Ivabradine Versus Digoxin in the Heart Rate Control in Patients With Permanent Atrial Fibrillation Under Treatment With Beta-blockers or Calcium Antagonists.PHASE3

COMPLETED · via Digoxin · NCT03718273

A Phase I, Open Label Study to Assess the Effects of TA-8995 on the Pharmacokinetics of Midazolam and Digoxin in Healthy Male SubjectsPHASE1

COMPLETED · via Digoxin · NCT02124954

An Open Label, Single Dose, Three Part Study to Assess the Effects of Rolapitant (1.8 mg/mL Rolapitant IV Solution) on the Pharmacokinetics of Digoxin (P-gp); Sulfasalazine (BCRP); and the Cooperstown Cocktail (Midazolam [CYP3A4], Omeprazole [CYP2C19], Warfarin [CYP2C9], Caffeine [CYP1A2], and Dextromethorphan [CYP2D6]) in Healthy SubjectsPHASE1

COMPLETED · via Digoxin · NCT02434861

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 SubjectsPHASE1

ACTIVE_NOT_RECRUITING · via Digoxin · NCT07567781

Effect of Baricitinib on the Pharmacokinetics of Digoxin in Healthy SubjectsPHASE1

COMPLETED · via Digoxin · NCT01859078

A Phase I, Open-label, Fixed-sequence, Drug Interaction Study to Investigate the Effect of Single and Multiple Oral Doses of LOXO-305 on the Pharmacokinetics of Multiple Oral Doses of Digoxin (P-Glycoprotein Substrate) in Healthy SubjectsPHASE1

COMPLETED · via Digoxin · NCT06194214

A Phase 1, Open-label Study to Evaluate Pharmacokinetic Drug-drug Interactions Between VX-548 and Midazolam and Digoxin in Healthy SubjectsPHASE1

COMPLETED · via Digoxin · NCT05541471

A Phase I Study to Assess Safety, Tolerability, Pharmacokinetics and Effect of Food on Multiple Rising Oral Doses of BI 1839100 (Single-blind, Randomised, Placebo-controlled, Parallel Group Design) and the Effect of Multiple Doses of BI 1839100 on the Single Dose Pharmacokinetics of Cytochrome P450 Substrate (Midazolam), a P Glycoprotein Substrate (Digoxin) and OATP Substrate (Rosuvastatin) Administered Orally (Open-label, Fixed-sequence) in Healthy Male SubjectsPHASE1

COMPLETED · via Digoxin · NCT05738291

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

congestive heart failureModerately supported
0.74
agreement 0.57–0.91
Clinical100%

Open Targets aggregate 0.60 · 1 independent evidence family

atrial fibrillationModerately supported
0.73
agreement 0.57–0.90
Clinical100%

Open Targets aggregate 0.59 · 1 independent evidence family

heart failureModerately supported
0.71
agreement 0.55–0.88
Clinical100%

Open Targets aggregate 0.58 · 1 independent evidence family

cardiovascular disorderModerately supported
0.68
agreement 0.52–0.84
Clinical100%

Open Targets aggregate 0.55 · 1 independent evidence family

ArrhythmiaModerately supported
0.62
agreement 0.46–0.79
Clinical100%

Open Targets aggregate 0.50 · 1 independent evidence family

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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

3

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. 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

  2. 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

  3. 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.