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Protein / target

Carbonic anhydrase 12

Encoded byCA12O43570Homo 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

Carbonate dehydratase

Strongest disease association

Isolated hyperchlorhidrosis

Via encoding gene CA12 · Genetic evidence · score 0.79

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

Reversible hydration of carbon dioxide

Subcellular location

MembraneCell membrane
Domains and Gene Ontology detail (9)

Domains & features

Alpha-carbonic anhydrase

Gene Ontology

  • Capical plasma membrane
  • Cbasolateral plasma membrane
  • Cmembrane
  • Cplasma membrane
  • Fcarbonate dehydratase activity
  • Fzinc ion binding
  • Pchloride ion homeostasis
  • Pestrous cycle

354 aa · 39 kDa · 2 isoforms

Biological roles

Reactome v97

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

Chloride transportGO
View supporting evidence

Chloride transport

  • ·chloride ion homeostasis
View underlying pathways (1)

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.

CYP24A1CA9SLC9A1SLC4A2CA4SLC2A1CA14RPF2VHLSLC4A4CA12

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 · 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.

Altitude Sickness1 medicine
Edema1 medicine
Epilepsy1 medicine
Glaucoma1 medicine
Glaucoma, Angle-Closure1 medicine
Heart Failure1 medicine
Seizures1 medicine

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.

Acetazolamide
ApprovedInhibitor

Carbonic anhydrase XII inhibitor

Indicated for Altitude Sickness, Edema, Epilepsy, Glaucoma

Direct interaction with this protein · 1 of 4 recorded protein targets

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 CA12

Gene-level evidence surfaced through the gene CA12that 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.

Isolated hyperchlorhidrosis
0.81Well supported

Genetic evidence dominant · Open Targets 0.68

Hypothyroidism
0.76Well supported

Genetic evidence dominant · Open Targets 0.46

Glaucoma
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.61

Dentures
0.72Moderately supported

Genetic evidence dominant · Open Targets 0.44

Epilepsy
0.57Moderately supported

Clinical evidence dominant · Open Targets 0.46

View evidence synthesis (5)
Isolated hyperchlorhidrosisWell supported
0.81
agreement 0.710.92
Genetic86%Somatic mutation14%Genetic literaturedup

Open Targets aggregate 0.68 · 2 independent evidence families · 1 not counted as duplicate

HypothyroidismWell supported
0.76
agreement 0.640.88
Genetic100%

Open Targets aggregate 0.46 · 1 independent evidence family

GlaucomaModerately supported
0.75
agreement 0.590.90
Clinical93%Literature7%

Open Targets aggregate 0.61 · 2 independent evidence families

DenturesModerately supported
0.72
agreement 0.600.84
Genetic100%

Open Targets aggregate 0.44 · 1 independent evidence family

EpilepsyModerately supported
0.57
agreement 0.420.73
Clinical99%Literature1%

Open Targets aggregate 0.46 · 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
Isolated hyperchlorhidrosis0.68
Glaucoma0.61
Epilepsy0.46
Hypothyroidism0.46
Dentures0.44
Heart Failure0.39

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)
ETHOXZOLAMIDEApproval
SULTHIAMEApproval
DICHLORPHENAMIDEApproval
ACETAZOLAMIDEApproval
ACETAZOLAMIDE SODIUMApproval

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 (11)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

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 Acetazolamide · NCT05802849

RECRUITING · via Acetazolamide · NCT02703220

RECRUITING · via Acetazolamide · NCT06091085

RECRUITING · via Acetazolamide · NCT05293600

ACTIVE_NOT_RECRUITING · via Acetazolamide · NCT00262470

NOT_YET_RECRUITING · via Acetazolamide · NCT06273397

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. Label change2026-07-14

    Label change: ACETAZOLAMIDE (ANDA040904)

    fda · regulatory · fda · via Acetazolamide

  2. Label change2026-07-01

    Label change: ACETAZOLAMIDE (ANDA040089)

    fda · regulatory · fda · via Acetazolamide

  3. Label change2026-06-05

    Label change: ACETAZOLAMIDE (ANDA202693)

    fda · regulatory · fda · via Acetazolamide

  4. Label change2024-07-26

    Label change: ACETAZOLAMIDE (ANDA202693)

    fda · regulatory · fda · via Acetazolamide

  5. Label change2024-07-26

    Label change: ACETAZOLAMIDE (ANDA202693)

    fda · regulatory · fda · via Acetazolamide

  6. Label change2024-01-25

    Label change: ACETAZOLAMIDE (ANDA040089)

    fda · regulatory · fda · via Acetazolamide

  7. New publication2023-07-18
    Treatment with GLP-1 receptor agonists is associated with significant weight loss and favorable headache outcomes in idiopathic intracranial hypertension.

    The journal of headache and pain · 2023 · 56 citations · Europe PMC · via Acetazolamide

  8. Label change2023-01-23

    Label change: ACETAZOLAMIDE (ANDA040904)

    fda · regulatory · fda · via Acetazolamide

  9. New publication2022-08-27
    Acetazolamide in Acute Decompensated Heart Failure with Volume Overload.

    The New England journal of medicine · 2022 · 374 citations · Europe PMC · via Acetazolamide

  10. New publication2014-04-01
    Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial.

    JAMA · 2014 · 363 citations · Europe PMC · via Acetazolamide

  11. Regulatory approval2008-12-10

    Approval: ACETAZOLAMIDE (ANDA040904)

    fda · regulatory · fda · via Acetazolamide

  12. Regulatory approval1995-02-28

    Approval: ACETAZOLAMIDE (ANDA040089)

    fda · regulatory · fda · via Acetazolamide

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.

Related family literature

1

Papers about “Carbonic Anhydrases” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.