Protein / target
Solute carrier family 12 member 3
Protein at a glance
Biological role
Sodium:potassium:chloride symporter
Strongest disease association
Gitelman Syndrome
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules.
View complete UniProt function annotationHide complete annotation
Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity)
Subcellular location
Domains and Gene Ontology detail (19)Hide
Gene Ontology
- Capical plasma membrane
- Ccytosol
- Cextracellular exosome
- Cmembrane
- Cplasma membrane
- FATP binding
- Fsodium:chloride symporter activity
- Fsodium:potassium:chloride symporter activity
- Pcell volume homeostasis
- Pchloride ion homeostasis
- Pchloride transmembrane transport
- Ppotassium ion homeostasis
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Chloride transport
- ·Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of so…
- ·chloride ion homeostasis
Ion channel gating
- ·sodium ion transmembrane transport
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Approved medicines with mapped indications
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.
Broader indication categories (1)Hide
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.
13 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
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.
Thiazide-sensitive sodium-chloride cotransporter inhibitor
Indicated for Angina Pectoris, Edema, Heart Failure, Hypertension
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
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 SLC12A3
Gene-level evidence surfaced through the gene SLC12A3 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.
View evidence synthesis (5)Hide
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.
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Drug development
13 compounds recorded · 13 approved
View all recorded compounds (10)Hide
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 molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (9)Hide
Raw Open Targets tractability assessment buckets, by modality.
Clinical trials
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)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
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.
- Label change
Label change: BISOPROLOL FUMARATE AND HYDROCHLOROTHIAZIDE (NDA020186)
- Label change
Label change: BISOPROLOL FUMARATE AND HYDROCHLOROTHIAZIDE (NDA020186)
- New publicationHydrochlorothiazide and Prevention of Kidney-Stone Recurrence.
- Safety communication
Drug Safety Update: Hydrochlorothiazide: risk of non-melanoma skin cancer, particularly in long-term use
- Supplemental approval
Supplemental approval: BISOPROLOL FUMARATE AND HYDROCHLOROTHIAZIDE (NDA020186)
- Supplemental approval
Supplemental approval: BISOPROLOL FUMARATE AND HYDROCHLOROTHIAZIDE (NDA020186)
- New publicationGenome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans.
- New publicationBlood pressure responses and metabolic effects of hydrochlorothiazide and atenolol.
- New publicationComparison of office, ambulatory, and home blood pressure antihypertensive response to atenolol and hydrochlorthiazide.
- Supplemental approval
Supplemental approval: BISOPROLOL FUMARATE AND HYDROCHLOROTHIAZIDE (NDA020186)
- Supplemental approval
Supplemental approval: BISOPROLOL FUMARATE AND HYDROCHLOROTHIAZIDE (NDA020186)
- Regulatory approval
Approval: BISOPROLOL FUMARATE AND HYDROCHLOROTHIAZIDE (NDA020186)
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.