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Protein / target

Carbonic anhydrase 4

Encoded byCA4P22748Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
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

Retinitis Pigmentosa

Via encoding gene CA4 · Genetic evidence · score 0.81

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

Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH.

View complete UniProt function annotation

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.

Approved medicines with mapped indications

2 medicines · 8 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.

Epilepsy2 medicines
Seizures2 medicines
Altitude Sickness1 medicine
Edema1 medicine
Glaucoma1 medicine
Glaucoma, Angle-Closure1 medicine
Heart Failure1 medicine
Migraine Disorders1 medicine

7 medicines meet Open Targets' target-level approved-medicine definition; the 2 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

2

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 IV inhibitor

Indicated for Altitude Sickness, Edema, Epilepsy, Glaucoma

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

topiramate
ApprovedInhibitor

Carbonic anhydrase IV inhibitor

Indicated for Epilepsy, Migraine Disorders, Seizures

Direct interaction with this protein · 1 of 37 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 CA4

Gene-level evidence surfaced through the gene CA4 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.

Retinitis Pigmentosa
0.81Well supported

Genetic evidence dominant · Open Targets 0.69

Epilepsy
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.61

Glaucoma
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Alcoholism
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.57

View evidence synthesis (4)
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

AlcoholismModerately supported
0.70
agreement 0.550.86
Clinical100%Literature0%

Open Targets aggregate 0.57 · 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
Retinitis Pigmentosa0.69
Epilepsy0.61
Glaucoma0.60
Alcoholism0.57

Drug development

7 compounds recorded · 7 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (7)
METHAZOLAMIDEApproval
ETHOXZOLAMIDEApproval
ACETAZOLAMIDE SODIUMApproval
DICHLORPHENAMIDEApproval
TOPIRAMATEApproval
SULTHIAMEApproval
ACETAZOLAMIDEApproval

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 (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
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

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)

ACTIVE_NOT_RECRUITING · via topiramate · NCT06799169

RECRUITING · via Acetazolamide · NCT05802849

RECRUITING · via Acetazolamide · NCT02703220

RECRUITING · via Acetazolamide · NCT06091085

ACTIVE_NOT_RECRUITING · via Acetazolamide · NCT00262470

NOT_YET_RECRUITING · via Acetazolamide · NCT06273397

UNKNOWN · via topiramate · NCT06089356

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 2 drugs that target 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. Regulatory approval2026-09-04

    Approval: TOPIRAMATE (ANDA219183)

    fda · regulatory · fda · via topiramate

  2. Product recall2026-08-31

    Recall (Class III): TOPIRAMATE

    fda · safety · fda · via topiramate

  3. Regulatory approval2026-07-22

    Approval: TOPIRAMATE (ANDA220943)

    fda · regulatory · fda · via topiramate

  4. Label change2026-07-14

    Label change: ACETAZOLAMIDE (ANDA040904)

    fda · regulatory · fda · via Acetazolamide

  5. Product recall2026-07-06

    Recall (Class III): TOPIRAMATE

    fda · safety · fda · via topiramate

  6. Supplemental approval2026-06-29

    Supplemental approval: PHENTERMINE AND TOPIRAMATE (NDA022580)

    fda · regulatory · fda · via topiramate

  7. Safety communication2024-06-20

    Drug Safety Update: Topiramate (Topamax): introduction of new safety measures, including a Pregnancy Prevention Programme

    mhra · safety · mhra · via topiramate

  8. 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

  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. Safety communication2022-07-21

    Drug Safety Update: Topiramate (Topamax): start of safety review triggered by a study reporting an increased risk of neurodevelopmental disabilities in children with prenatal exposure

    mhra · safety · mhra · via topiramate

  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. New publication1999-06-01
    A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group.

    Neurology · 1999 · 245 citations · Europe PMC · via topiramate

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.