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Protein / target

Solute carrier family 12 member 1

Encoded bySLC12A1Q13621Homo 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

Sodium:potassium:chloride symporter

Strongest disease association

Bartter Syndrome

Via encoding gene SLC12A1 · Genetic literature evidence · score 0.91

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

Renal sodium, potassium and chloride non-electrogenic ion symporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation.

View complete UniProt function annotation

Renal sodium, potassium and chloride non-electrogenic ion symporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation (PubMed:21321328). It can substitute NH4(+) for K(+), enabling NH4(+) apical transmembrane transport in the medullary thick ascending limb (MTAL). This function is crucial for maintaining ammonium homeostasis by the kidney, particularly during metabolic acidosis (By similarity)

Subcellular location

Apical cell membrane
Domains and Gene Ontology detail (16)

Gene Ontology

  • Capical plasma membrane
  • Cextracellular exosome
  • Cmembrane
  • Cplasma membrane
  • Fsodium:ammonium:chloride symporter activity
  • Fsodium:potassium:chloride symporter activity
  • Pammonium homeostasis
  • Pcell volume homeostasis
  • Pchloride ion homeostasis
  • Pchloride transmembrane transport
  • Pmonoatomic ion transmembrane transport
  • Ppotassium ion homeostasis

1099 aa · 121 kDa · 3 isoforms

Biological roles

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

Ion channel gatingGOChloride transportGO
View supporting evidence

Ion channel gating

  • ·monoatomic ion transmembrane transport
  • ·sodium ion transmembrane transport

Chloride transport

  • ·chloride ion homeostasis

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

Approved medicines with mapped indications

1 medicine · 7 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.

Fibrosis1 medicine
Heart Failure1 medicine
Hypertension1 medicine
Liver Cirrhosis1 medicine
Nephrotic Syndrome1 medicine
Syndrome1 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.

furosemide
Narrow target profileApprovedInhibitor

Sodium-(potassium)-chloride cotransporter 2 inhibitor

Indicated for Fibrosis, Heart Failure, Hypertension, Liver Cirrhosis

Direct interaction with this protein · Only this protein recorded as a target

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 SLC12A1

Gene-level evidence surfaced through the gene SLC12A1 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.

Bartter Syndrome
0.91Well supported

Genetic evidence dominant · Open Targets 0.72

Nephrotic Syndrome
0.82Well supported

Clinical evidence dominant · Open Targets 0.63

Hypertension
0.76Well supported

Clinical evidence dominant · Open Targets 0.62

Heart Failure
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Kidney Diseases
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

View evidence synthesis (5)
Bartter SyndromeWell supported
0.91
agreement 0.801.00
Genetic61%Animal model18%Pathway18%Literature3%Genetic literaturedup

Open Targets aggregate 0.72 · 4 independent evidence families · 1 not counted as duplicate

Nephrotic SyndromeWell supported
0.82
agreement 0.690.95
Clinical71%Animal model28%Literature0%

Open Targets aggregate 0.63 · 3 independent evidence families

HypertensionWell supported
0.76
agreement 0.610.92
Clinical92%Literature8%

Open Targets aggregate 0.62 · 2 independent evidence families

Heart FailureWell supported
0.76
agreement 0.600.91
Clinical95%Literature5%

Open Targets aggregate 0.61 · 2 independent evidence families

Kidney DiseasesModerately supported
0.74
agreement 0.580.89
Clinical97%Literature3%

Open Targets aggregate 0.60 · 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
Bartter Syndrome0.72
Nephrotic Syndrome0.63
Hypertension0.62
Heart Failure0.61
Kidney Diseases0.60
Liver Cirrhosis0.60
Cardiovascular Diseases0.54

Drug development

5 compounds recorded · 5 approved

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 (5)
ETHACRYNIC ACIDApproval
TORSEMIDEApproval
ETHACRYNATE SODIUMApproval
BUMETANIDEApproval
FUROSEMIDEApproval

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 Druggable Family support this modality.

AntibodiesEmerging

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

View underlying tractability evidence (5)
SM · Approved DrugSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMM

Raw Open Targets tractability assessment buckets, by modality.

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 furosemide · NCT04706910

ACTIVE_NOT_RECRUITING · via furosemide · NCT03753204

ENROLLING_BY_INVITATION · via furosemide · NCT06821594

NOT_YET_RECRUITING · via furosemide · NCT06273397

ClinicalTrials.gov via the drug-target graph.

What's happening now

8

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 changed2026-08-05

    The Role of Furosemide Stress Test in Predicting Acute Kidney Injury Progression and Need for Renal Replacement Therapy in Patients Followed in the Intensive Care Clinic

    Status changed to Completed · ClinicalTrials.gov · via furosemide

  2. Indication expanded2026-07-23

    Indication expansion: FUROSEMIDE INJECTION 80 MG/ 10 ML (NDA209988)

    fda · regulatory · fda · via furosemide

  3. Regulatory approval2026-05-29

    Approval: Bopediat (EMA)

    ema · regulatory · ema · via furosemide

  4. Indication expanded2025-12-22

    Indication expansion: FUROSEMIDE INJECTION 80 MG/ 10 ML (NDA209988)

    fda · regulatory · fda · via furosemide

  5. Indication expanded2025-03-06

    Indication expansion: FUROSEMIDE INJECTION 80 MG/ 10 ML (NDA209988)

    fda · regulatory · fda · via furosemide

  6. Indication expanded2024-08-09

    Indication expansion: FUROSEMIDE INJECTION 80 MG/ 10 ML (NDA209988)

    fda · regulatory · fda · via furosemide

  7. Regulatory approval2022-10-07

    Approval: FUROSEMIDE INJECTION 80 MG/ 10 ML (NDA209988)

    fda · regulatory · fda · via furosemide

  8. New publication2011-03-01
    Diuretic strategies in patients with acute decompensated heart failure.

    The New England journal of medicine · 2011 · 1,106 citations · Europe PMC · via furosemide

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.