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Protein / target

Sodium/potassium-transporting ATPase subunit alpha-1

Encoded byATP1A1P05023Homo 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

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

Via encoding gene ATP1A1 · Genetic evidence · score 0.88

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

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.

View complete UniProt function annotation

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 gatingGO
View supporting evidence

Ion channel gating

  • ·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.

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.

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 ATP1B2, ATP1B1, ATP1A2 +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 ATP1A1

Gene-level evidence surfaced through the gene ATP1A1 that 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.

Charcot-Marie-tooth disease, axonal, type 2DD
0.88Well supported

Genetic evidence dominant · Open Targets 0.78

Hypomagnesemia, seizures, and intellectual disability 2
0.85Well supported

Genetic evidence dominant · Open Targets 0.72

Atrial Fibrillation
0.77Well supported

Clinical evidence dominant · Open Targets 0.60

Heart Failure
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Cardiovascular Diseases
0.68Moderately supported

Clinical evidence dominant · Open Targets 0.55

View evidence synthesis (5)
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

Heart FailureModerately supported
0.74
agreement 0.590.90
Clinical98%Literature2%

Open Targets aggregate 0.60 · 2 independent evidence families

Cardiovascular DiseasesModerately supported
0.68
agreement 0.530.84
Clinical99%Literature1%

Open Targets aggregate 0.55 · 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
Charcot-Marie-tooth disease, axonal, type 2DD0.78
Hypomagnesemia, seizures, and intellectual disability 20.72
Atrial Fibrillation0.60
Heart Failure0.60
Cardiovascular Diseases0.55
Adrenocortical Adenoma0.55
Neurodegenerative Diseases0.53

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)
DIGOXINApproval
DIGITOXINApproval
LANATOSIDE CApproval
DESLANOSIDEApproval
ACETYLDIGITOXINApproval
ISTAROXIMEPhase 2 3

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 half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (12)
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

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

TERMINATED · via Digoxin · NCT05014087

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. Trial status changed2026-08-19

    A Phase 1, Open-Label, Two-Cohort Study to Assess the Effect of a Strong CYP3A4 Inducer on the Pharmacokinetics of Atumelnant and the Effect of Atumelnant on the Pharmacokinetics of CYP3A4, P-gp, and MATE1/2-K Substrates in Healthy Participants

    Status changed to Completed · ClinicalTrials.gov · via Digoxin

  2. Label change2026-08-10

    Label change: DIGOXIN (ANDA040481)

    fda · regulatory · fda · via Digoxin

  3. Trial status changed2026-07-30

    A Phase 2a Biomarker-Driven Trial of Oral Digoxin in Individuals With Amyotrophic Lateral Sclerosis (ALS) - The Acacia Trial, an ALS MyMatch Trial

    Status changed to Completed · ClinicalTrials.gov · via Digoxin

  4. 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

  5. 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

  6. 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

  7. Label change2020-07-16

    Label change: DIGOXIN (ANDA040481)

    fda · regulatory · fda · via Digoxin

  8. Label change2020-07-16

    Label change: DIGOXIN (ANDA040481)

    fda · regulatory · fda · via Digoxin

  9. Label change2016-11-02

    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.