Protein / target

Carbonic anhydrase 4

CA4P22748Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Carbonate dehydratase activity

Strongest disease association

retinitis pigmentosa

Genetic evidence · score 0.81

Therapeutic maturity

Clinically validated target

7 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

7 approved

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

Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH (PubMed:15563508, PubMed:16686544, PubMed:16807956, PubMed:17127057, PubMed:17314045, PubMed:17652713, PubMed:17705204, PubMed:18618712, PubMed:19186056, PubMed:19206230, PubMed:7625839). May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis (PubMed:15563508). It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid (PubMed:15563508)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (18)

Domains & features

Alpha-carbonic anhydrase

Gene Ontology

  • Capical plasma membrane
  • Cbrush border membrane
  • Ccell surface
  • Cendoplasmic reticulum-Golgi intermediate compartment
  • Cexternal side of plasma membrane
  • Cextracellular exosome
  • CGolgi apparatus
  • Cmembrane
  • Cperinuclear region of cytoplasm
  • Cplasma membrane
  • Crough endoplasmic reticulum
  • Csecretory granule membrane

312 aa · 35 kDa · 2 isoforms

Biological roles

Reactome v97

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

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.

CA3SLC4A4CYP24A1PKD2L1FSCN2PRSS12RP9PRPF31TALDO1IMPDH1CA4

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.

Acetazolamide
ApprovedInhibitor

Carbonic anhydrase IV inhibitor

Appears in clinical studies involving Seizure, glaucoma, edema, angle-closure glaucoma

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

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.

retinitis pigmentosa0.81

Genetic · overall 0.69

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

epilepsy0.99

Clinical · overall 0.61

glaucoma0.98

Clinical · overall 0.60

Seizure0.98

Clinical · overall 0.59

angle-closure glaucoma0.98

Clinical · overall 0.59

altitude sickness0.97

Clinical · overall 0.59

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

edema0.59

Clinical

migraine disorder0.58

Clinical

alcohol dependence0.57

Clinical

Lennox-Gastaut syndrome0.51

Clinical

Show all associations
retinitis pigmentosa0.69
epilepsy0.61
glaucoma0.60
Seizure0.59
angle-closure glaucoma0.59
altitude sickness0.59
edema0.59
migraine disorder0.58
alcohol dependence0.57
Lennox-Gastaut syndrome0.51

Open Targets ranks 390 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 · 7 total

METHAZOLAMIDEApproval

glaucoma · open-angle glaucoma · type 2 diabetes mellitus

ETHOXZOLAMIDEApproval

duodenal ulcer

ACETAZOLAMIDE SODIUMApproval

Seizure · angle-closure glaucoma · edema

DICHLORPHENAMIDEApproval

glaucoma · paramyotonia congenita of Von Eulenburg · hyperkalemic periodic paralysis

TOPIRAMATEApproval

epilepsy · migraine disorder · Lennox-Gastaut syndrome

SULTHIAMEApproval

epilepsy · obstructive sleep apnea syndrome · childhood-onset epilepsy syndrome

ACETAZOLAMIDEApproval

Seizure · glaucoma · edema

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

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 Acetazolamide · NCT02703220

COMPLETED · via Acetazolamide · NCT05589792

COMPLETED · via Acetazolamide · NCT00223691

COMPLETED · via Acetazolamide · NCT00714740

TERMINATED · via Acetazolamide · NCT02466074

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.

retinitis pigmentosaWell supported
0.81
agreement 0.680.95
Genetic97%Literature3%Genetic literaturedup

Open Targets aggregate 0.69 · 2 independent evidence families · 1 not counted as duplicate

epilepsyModerately supported
0.75
agreement 0.590.90
Clinical100%Literature1%

Open Targets aggregate 0.61 · 2 independent evidence families

glaucomaModerately supported
0.74
agreement 0.580.89
Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

SeizureModerately supported
0.73
agreement 0.580.89
Clinical100%Literature0%

Open Targets aggregate 0.59 · 2 independent evidence families

angle-closure glaucomaModerately supported
0.73
agreement 0.570.90
Clinical100%

Open Targets aggregate 0.59 · 1 independent evidence family

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

15

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. 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. Regulatory approval2014-12-19

    Approval: ACETAZOLAMIDE (ANDA202693)

    fda · regulatory · fda · via Acetazolamide

  11. 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

  12. Regulatory approval2008-12-10

    Approval: ACETAZOLAMIDE (ANDA040904)

    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.