Protein / target

Sodium/potassium-transporting ATPase subunit alpha-1

ATP1A1P05023Homo sapiensSwiss-Prot
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

Primary system

Nervous system

Strongest disease association

Charcot-Marie-tooth disease, axonal, type 2DD

Genetic evidence · score 0.88

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

Catalytic subunit of the Na(+)/K(+)-ATPase pump that hydrolyzes ATP to exchange ions across the plasma membrane, exporting 3 Na(+) and importing 2 K(+) per cycle against electrochemical gradients (PubMed:29499166, PubMed:30388404, PubMed:35803952). It undergoes ATP-driven conformational changes that allow alternating binding and release of Na(+) and K(+) ions across the membrane (PubMed:35803952). This process maintains essential Na(+) and K(+) gradients for membrane potential and cellular function. Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity)

Subcellular location

Cell membraneBasolateral cell membraneCell membrane, sarcolemmaCell projection, axonMelanosome
Domains and Gene Ontology detail (46)

Gene Ontology

  • Capical plasma membrane
  • Caxon
  • Cbasolateral plasma membrane
  • Cendoplasmic reticulum
  • Cextracellular exosome
  • Cextracellular vesicle
  • CGolgi apparatus
  • Clateral plasma membrane
  • Cmelanosome
  • Cmembrane
  • Cmembrane raft
  • Corganelle membrane

1023 aa · 113 kDa · 4 isoforms

Biological roles

Reactome v97

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

Ion channel gatingGOSynaptic signallingGO
View supporting evidence

Ion channel gating

  • ·potassium ion transmembrane transport
  • ·sodium ion transmembrane transport

Synaptic signalling

  • ·postsynaptic density
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.

ATP1B1FXYD2ATP1B3ATP1B2ATP1B4ATP1A3MAPK1FXYD1MAPK3ATP1A2ATP1A1

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 ATP1B2, ATP1B1, ATP1A2 +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.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

Charcot-Marie-tooth disease, axonal, type 2DD0.88

Genetic · overall 0.78

hypomagnesemia, seizures, and intellectual disability 20.85

Genetic · overall 0.72

Intellectual disability0.76

Genetic literature · overall 0.54

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 0.60

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.

aldosterone-producing adrenal cortex adenoma0.55

Somatic mutation

neurodegenerative disease0.53

Pathway

Show all associations
Charcot-Marie-tooth disease, axonal, type 2DD0.78
hypomagnesemia, seizures, and intellectual disability 20.72
atrial fibrillation0.60
congestive heart failure0.60
heart failure0.58
cardiovascular disorder0.55
aldosterone-producing adrenal cortex adenoma0.55
Intellectual disability0.54
neurodegenerative disease0.53
Arrhythmia0.50

Open Targets ranks 519 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

DIGOXINApproval

congestive heart failure · atrial fibrillation · heart failure

DIGITOXINApproval

cardiovascular disorder · Arrhythmia · heart failure

LANATOSIDE CApproval

cardiovascular disorder

DESLANOSIDEApproval

cardiovascular disorder · Arrhythmia · heart failure

ACETYLDIGITOXINApproval

cardiovascular disorder · congestive heart failure

ISTAROXIMEPhase 2 3

heart disorder · heart failure · heart failure

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database UbiquitinationPR · Half-life DataPR · 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.

Show remaining trials (24)

RECRUITING · via Digoxin · NCT06588699

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.

Charcot-Marie-tooth disease, axonal, type 2DDWell supported
0.88
agreement 0.741.00
Genetic100%Literature0%Genetic literaturedup

Open Targets aggregate 0.78 · 2 independent evidence families · 1 not counted as duplicate

hypomagnesemia, seizures, and intellectual disability 2Well supported
0.85
agreement 0.730.97
Genetic100%Genetic literaturedup

Open Targets aggregate 0.72 · 1 independent evidence family · 1 not counted as duplicate

atrial fibrillationWell supported
0.77
agreement 0.640.90
Clinical85%Animal model14%Literature1%

Open Targets aggregate 0.60 · 3 independent evidence families

congestive heart failureModerately supported
0.74
agreement 0.590.90
Clinical98%Literature2%

Open Targets aggregate 0.60 · 2 independent evidence families

heart failureModerately supported
0.72
agreement 0.560.87
Clinical98%Literature2%

Open Targets aggregate 0.58 · 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 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.