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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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CA2
carbonic anhydrase 2
Chromosome 8 Β· 8q21.2
NCBI Gene: 760Ensembl: ENSG00000104267.11HGNC: HGNC:1373UniProt: P00918
272PubMed Papers
21Diseases
11Drugs
23Pathogenic Variants
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
plasma membraneapical part of cellprotein bindingzinc ion bindingOsteopetrosis with renal tubular acidosisautosomal recessive osteopetrosis 3glaucomaepilepsy
✦AI Summary

CA2 (carbonic anhydrase 2) is a cytosolic enzyme that catalyzes the reversible hydration of carbon dioxide to bicarbonate and protons, playing essential roles in pH regulation and ion transport 1. The enzyme functions through zinc-dependent catalysis and can also hydrate cyanamide to urea 2. CA2 stimulates chloride-bicarbonate exchange activity of SLC26A6 and contributes to intracellular pH regulation in duodenal epithelium during proton-coupled peptide absorption 3. The enzyme is essential for bone resorption and osteoclast differentiation, and is involved in regulating fluid secretion into the anterior chamber of the eye 4. CA2 deficiency is associated with osteopetrosis, autosomal recessive 3, a rare bone disease characterized by impaired bone resorption due to osteoclast dysfunction. The enzyme's wide tissue distribution and multiple cellular locations (cytoplasm, plasma membrane, apical cell regions) reflect its fundamental role in cellular pH homeostasis and bicarbonate transport processes. CA2's involvement in bone metabolism makes it clinically significant for understanding bone remodeling disorders and potential therapeutic targets.

Sources cited
1
CA2 catalyzes the reversible hydration of carbon dioxide
PMID: 11327835
2
CA2 can also hydrate cyanamide to urea
PMID: 10550681
3
CA2 stimulates chloride-bicarbonate exchange activity of SLC26A6
PMID: 15990874
4
CA2 is essential for bone resorption and osteoclast differentiation
PMID: 15300855
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
Osteopetrosis with renal tubular acidosisOpen Targets
0.79Strong
autosomal recessive osteopetrosis 3Open Targets
0.79Strong
glaucomaOpen Targets
0.62Moderate
epilepsyOpen Targets
0.61Moderate
ocular hypertensionOpen Targets
0.61Moderate
open-angle glaucomaOpen Targets
0.60Moderate
altitude sicknessOpen Targets
0.60Moderate
SeizureOpen Targets
0.60Moderate
migraine disorderOpen Targets
0.60Moderate
angle-closure glaucomaOpen Targets
0.59Moderate
edemaOpen Targets
0.59Moderate
alcohol dependenceOpen Targets
0.56Moderate
Lennox-Gastaut syndromeOpen Targets
0.49Moderate
congestive heart failureOpen Targets
0.46Moderate
osteopetrosisOpen Targets
0.46Moderate
obesityOpen Targets
0.41Moderate
partial epilepsyOpen Targets
0.38Weak
HeadacheOpen Targets
0.37Weak
Intellectual disabilityOpen Targets
0.37Weak
rheumatic diseaseOpen Targets
0.37Weak
Osteopetrosis, autosomal recessive 3UniProt
Pathogenic Variants23
NM_000067.3(CA2):c.681del (p.Lys227fs)Pathogenic
Osteopetrosis with renal tubular acidosis|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 227
NM_000067.3(CA2):c.232+1G>APathogenic
Osteopetrosis with renal tubular acidosis|not provided|Osteopetrosis
β˜…β˜…β˜†β˜†2025
NM_000067.3(CA2):c.275A>C (p.Gln92Pro)Likely pathogenic
Osteopetrosis with renal tubular acidosis|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 92
NM_000067.3(CA2):c.610G>T (p.Glu204Ter)Pathogenic
Osteopetrosis with renal tubular acidosis
β˜…β˜…β˜†β˜†2024β†’ Residue 204
NM_000067.3(CA2):c.630_641delinsCACA (p.Leu211fs)Pathogenic
not provided|Osteopetrosis with renal tubular acidosis
β˜…β˜…β˜†β˜†2023β†’ Residue 211
NM_000067.3(CA2):c.579C>G (p.Tyr193Ter)Likely pathogenic
Osteopetrosis with renal tubular acidosis|Neurodevelopmental delay
β˜…β˜…β˜†β˜†2019β†’ Residue 193
NM_000067.3(CA2):c.381T>G (p.Tyr127Ter)Pathogenic
Osteopetrosis with renal tubular acidosis
β˜…β˜†β˜†β˜†2024β†’ Residue 127
NM_000067.3(CA2):c.672del (p.Lys224fs)Likely pathogenic
Osteopetrosis with renal tubular acidosis
β˜…β˜†β˜†β˜†2024β†’ Residue 224
NM_000067.3(CA2):c.233-1G>ALikely pathogenic
Osteopetrosis with renal tubular acidosis
β˜…β˜†β˜†β˜†2024
NM_000067.3(CA2):c.165_166insGAGGA (p.Ser56fs)Likely pathogenic
Osteopetrosis with renal tubular acidosis
β˜…β˜†β˜†β˜†2024β†’ Residue 56
NM_000067.3(CA2):c.445-2_445-1delinsTCLikely pathogenic
Osteopetrosis with renal tubular acidosis
β˜…β˜†β˜†β˜†2024
NM_000067.3(CA2):c.314C>G (p.Ser105Ter)Likely pathogenic
Osteopetrosis with renal tubular acidosis
β˜…β˜†β˜†β˜†2024β†’ Residue 105
NM_000067.3(CA2):c.232+2T>GLikely pathogenic
CA2-related disorder
β˜…β˜†β˜†β˜†2022
NM_000067.3(CA2):c.143_146del (p.Ser48fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 48
NM_000067.3(CA2):c.21C>A (p.Tyr7Ter)Pathogenic
Osteopetrosis with renal tubular acidosis
β˜…β˜†β˜†β˜†2017β†’ Residue 7
NM_000067.3(CA2):c.2T>G (p.Met1Arg)Likely pathogenic
Neurodevelopmental delay
β˜…β˜†β˜†β˜†β†’ Residue 1
NM_000067.3(CA2):c.153T>A (p.Tyr51Ter)Likely pathogenic
CA2-related disorder
β˜†β˜†β˜†β˜†2023β†’ Residue 51
NM_000067.3(CA2):c.621del (p.Trp208fs)Pathogenic
Osteopetrosis with renal tubular acidosis
β˜†β˜†β˜†β˜†2003β†’ Residue 208
NM_000067.3(CA2):c.319C>T (p.His107Tyr)Pathogenic
Osteopetrosis with renal tubular acidosis
β˜†β˜†β˜†β˜†1996β†’ Residue 107
NM_000067.3(CA2):c.120T>G (p.Tyr40Ter)Pathogenic
Osteopetrosis with renal tubular acidosis
β˜†β˜†β˜†β˜†1995β†’ Residue 40
View on ClinVar β†—
Drug Targets11
ACETAZOLAMIDEApproved
Carbonic anhydrase I inhibitor
Seizure
ACETAZOLAMIDE SODIUMApproved
Carbonic anhydrase I inhibitor
angle-closure glaucoma
BRINZOLAMIDEApproved
Carbonic anhydrase II inhibitor
glaucoma
DICHLORPHENAMIDEApproved
Carbonic anhydrase I inhibitor
DORZOLAMIDEApproved
Carbonic anhydrase II inhibitor
open-angle glaucoma
DORZOLAMIDE HYDROCHLORIDEApproved
Carbonic anhydrase II inhibitor
ocular hypertension
ETHOXZOLAMIDEApproved
Carbonic anhydrase inhibitor
METHAZOLAMIDEApproved
Carbonic anhydrase I inhibitor
glaucoma
POLMACOXIBApproved
Carbonic anhydrase I inhibitor
rheumatic disease
SULTHIAMEApproved
Carbonic anhydrase inhibitor
epilepsy
TOPIRAMATEApproved
Glutamate receptor ionotropic AMPA antagonist
epilepsy
Related Genes
CLCN7Protein interaction100%TCIRG1Protein interaction96%PLEKHM1Protein interaction92%SLC9A1Protein interaction85%CBSProtein interaction82%CA1Protein interaction80%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
23%
Brain
10%
Lung
3%
Heart
3%
Ovary
0%
Gene Interaction Network
Click a node to explore
CA2CLCN7TCIRG1PLEKHM1SLC9A1CBSCA1
PROTEIN STRUCTURE
Preparing viewer…
PDB3K34 Β· 0.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.49LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.04 [0.73–1.49]
RankingsWhere CA2 stands among ~20K protein-coding genes
  • #1,349of 20,598
    Most Researched272 Β· top 10%
  • #140of 1,025
    FDA-Approved Drug Targets11 Β· top quartile
  • #2,034of 5,498
    Most Pathogenic Variants23
  • #15,124of 17,882
    Most Constrained (LOEUF)1.49
Genes detectedCA2
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
CRAC channelopathies.
PMID: 20111871
Pflugers Arch Β· 2010
1.00
2
Effect of Methoxsalen on Ca²⁺ Homeostasis and Viability in Human Osteosarcoma Cells.
PMID: 28629211
Chin J Physiol Β· 2017
0.90
3
The Ca2+ concentration impacts the cytokine production of mouse and human lymphoid cells and the polarization of human macrophages in vitro.
PMID: 36827279
PLoS One Β· 2023
0.84
4
Targeting Ca2+ cycling proteins and the action potential in heart failure by gene transfer.
PMID: 12479247
Basic Res Cardiol Β· 2002
0.80
5
Na+/Ca2+ exchangers regulate the migration and proliferation of human gastric myofibroblasts.
PMID: 23907822
Am J Physiol Gastrointest Liver Physiol Β· 2013
0.76