CA3

gene
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Also known as Car3CAIII

Summary

CA3 (carbonic anhydrase 3, HGNC:1374) is a protein-coding gene on chromosome 8q21.2, encoding Carbonic anhydrase 3 (P07451). Reversible hydration of carbon dioxide.

Carbonic anhydrase III (CAIII) is a member of a multigene family (at least six separate genes are known) that encodes carbonic anhydrase isozymes. These carbonic anhydrases are a class of metalloenzymes that catalyze the reversible hydration of carbon dioxide and are differentially expressed in a number of cell types. The expression of the CA3 gene is strictly tissue specific and present at high levels in skeletal muscle and much lower levels in cardiac and smooth muscle. A proportion of carriers of Duchenne muscle dystrophy have a higher CA3 level than normal. The gene spans 10.3 kb and contains seven exons and six introns.

Source: NCBI Gene 761 — RefSeq curated summary.

At a glance

  • GWAS associations: 5
  • Clinical variants (ClinVar): 25 total
  • Druggable target: yes — 34 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_005181

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:1374
Approved symbolCA3
Namecarbonic anhydrase 3
Location8q21.2
Locus typegene with protein product
StatusApproved
AliasesCar3, CAIII
Ensembl geneENSG00000164879
Ensembl biotypeprotein_coding
OMIM114750
Entrez761

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000285381, ENST00000520921, ENST00000522207, ENST00000967721, ENST00000967722

RefSeq mRNA: 1 — MANE Select: NM_005181 NM_005181

CCDS: CCDS6238

Canonical transcript exons

ENST00000285381 — 7 exons

ExonStartEnd
ENSE000010189778544403485444126
ENSE000010189858544803485449040
ENSE000010189878544207385442191
ENSE000010189888544614285446297
ENSE000010189938544515685445218
ENSE000017251118543885985438943
ENSE000035079018543971285439909

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 99.89.

FANTOM5 (CAGE): breadth broad, TPM avg 11.0631 / max 2928.8440, expressed in 244 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
8961311.0631244

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
skeletal muscle tissue of rectus abdominisUBERON:000451199.89gold quality
hindlimb stylopod muscleUBERON:000425299.83gold quality
vastus lateralisUBERON:000137999.69gold quality
biceps brachiiUBERON:000150799.64gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450299.59gold quality
quadriceps femorisUBERON:000137799.55gold quality
diaphragmUBERON:000110399.40gold quality
skeletal muscle tissueUBERON:000113499.35gold quality
gastrocnemiusUBERON:000138899.34gold quality
gluteal muscleUBERON:000200099.31gold quality
triceps brachiiUBERON:000150999.24gold quality
muscle organUBERON:000163098.59gold quality
skeletal muscle organUBERON:001489298.59gold quality
body of tongueUBERON:001187698.33gold quality
muscle of legUBERON:000138398.23gold quality
deltoidUBERON:000147698.18gold quality
tibialis anteriorUBERON:000138596.40gold quality
right lungUBERON:000216795.46gold quality
muscle tissueUBERON:000238593.52gold quality
tongueUBERON:000172390.13gold quality
mucosa of stomachUBERON:000119986.33gold quality
upper lobe of left lungUBERON:000895286.09gold quality
upper lobe of lungUBERON:000894885.70gold quality
trabecular bone tissueUBERON:000248385.69gold quality
superior surface of tongueUBERON:000737182.62gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099182.11gold quality
left uterine tubeUBERON:000130381.92gold quality
lower lobe of lungUBERON:000894981.74gold quality
minor salivary glandUBERON:000183080.65gold quality
adipose tissue of abdominal regionUBERON:000780878.65gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3no0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AR, MECOM

miRNA regulators (miRDB)

59 targeting CA3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3646100.0073.565283
HSA-MIR-29A-3P100.0073.111835
HSA-MIR-29B-3P100.0073.181833
HSA-MIR-29C-3P100.0073.151833
HSA-MIR-200B-3P100.0073.312693
HSA-MIR-200C-3P100.0073.352685
HSA-MIR-429100.0073.442698
HSA-MIR-318599.9968.121959
HSA-MIR-4778-3P99.9370.401818
HSA-MIR-797899.8666.90856
HSA-MIR-3663-3P99.8470.39798
HSA-MIR-5010-3P99.8370.602357
HSA-MIR-430799.8270.453374
HSA-MIR-4659A-3P99.8072.624248
HSA-MIR-4659B-3P99.8072.624248
HSA-MIR-808499.7369.571760
HSA-MIR-120099.7170.421838
HSA-MIR-518A-5P99.7069.012209
HSA-MIR-52799.7069.012209
HSA-MIR-472999.6972.184233
HSA-MIR-378A-5P99.6566.331311
HSA-MIR-6512-3P99.6566.071468
HSA-MIR-6720-5P99.6566.221459
HSA-MIR-607399.6070.36793
HSA-MIR-510-3P99.5470.062965
HSA-MIR-7159-5P99.5372.122472
HSA-MIR-6833-5P99.5068.931161
HSA-MIR-3140-5P99.3969.041136
HSA-MIR-391199.3866.951087
HSA-MIR-6505-3P99.3467.391071

Literature-anchored findings (GeneRIF, showing 16)

  • Crystallization and preliminary X-ray analysis of human carbonic anhydrase III (PMID:11976500)
  • Data show that inserting histidine residues into the active site cavity of carbonic anhydrase II or III results in rates of proton transfer to the zinc-bound hydroxide that are antagonistic or suppressive with respect to the corresponding single mutants. (PMID:12171926)
  • Proton transfer within the active-site cavity of carbonic anhydrase III (PMID:12484342)
  • myoglobin/carbonic anhydrase III ratio in the blood proved to be a more specific indicator for myocardial damage than myoglobin alone after myocardial infarction. (PMID:12745799)
  • CAIII expression is upregulated in kidney cortex samples from the end-stage kidney of a patient with Dent’s disease owing to the G506E mutation of CLCN5 (PMID:18322545)
  • CAIII promotes transformation and invasion capability in hepatoma cells through FAK signaling pathway. (PMID:18444244)
  • The level of CAIII is specifically insufficient in the skeletal muscle of myasthenia gravis patients. (PMID:19301202)
  • The carbonic anhydrase CA3 isoform displayed an increased abundance during muscle aging, which was independently verified by immunoblotting of differently aged human skeletal muscle samples. (PMID:22797148)
  • The generation of CA III and IV autoantibodies, antioxidant enzymes, and cytokines might influence each other. (PMID:23049597)
  • Report that anti-CAIII antibodies may be useful for diagnosing microscopic polyangiitis. (PMID:23981757)
  • this study detected the formation and colocalization of 6-nitrotryptophan-containing proteins and CAIII in the skin of atopic dermatitis patients, not only in the lesional part but also in the nonlesional part, through histochemical analyses (PMID:24838180)
  • CAIII and Hsp70 expressions were higher in LPRD patients that in non-LPRD patients, suggesting the possibility as one of biomomarker in LPRD diagnosis. (PMID:26847302)
  • these data clearly suggests that CAIII serves as an important antioxidant critical in protecting NP cells against oxidative stress-induced injury. (PMID:29559661)
  • Carbonic Anhydrase III Promotes Cell Migration and Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma. (PMID:32183030)
  • Carbonic anhydrase III is a new target of HIF1alpha in prostate cancer model. (PMID:32777521)
  • Carbonic anhydrase 2 and 3 as risk biomarkers for dilated cardiomyopathy associated heart failure. (PMID:35016406)

Cross-species orthologs

18 orthologs

OrganismSymbolGene ID
danio_reriocahzENSDARG00000011166
danio_rerioca2ENSDARG00000014488
mus_musculusCar3ENSMUSG00000027559
rattus_norvegicusCar3ENSRNOG00000010079
drosophila_melanogasterCAH13FBGN0033542
drosophila_melanogasterCAH14FBGN0034554
drosophila_melanogasterCAH15FBGN0034560
drosophila_melanogasterCAH7FBGN0037788
drosophila_melanogasterCAH8FBGN0038956
drosophila_melanogasterCAH4FBGN0039235
drosophila_melanogasterCAH9FBGN0039486
drosophila_melanogasterCAH6FBGN0039838
drosophila_melanogasterCAH16FBGN0040628
drosophila_melanogasterCAH5FBGN0040629
drosophila_melanogasterCARPBFBGN0052698
caenorhabditis_elegansWBGENE00000279
caenorhabditis_elegansWBGENE00000283
caenorhabditis_eleganscah-6WBGENE00000284

Paralogs (14): CA11 (ENSG00000063180), CA12 (ENSG00000074410), CA2 (ENSG00000104267), CA9 (ENSG00000107159), CA14 (ENSG00000118298), CA6 (ENSG00000131686), CA1 (ENSG00000133742), CA10 (ENSG00000154975), CA4 (ENSG00000167434), CA7 (ENSG00000168748), CA5B (ENSG00000169239), CA5A (ENSG00000174990), CA8 (ENSG00000178538), CA13 (ENSG00000185015)

Protein

Protein identifiers

Carbonic anhydrase 3P07451 (reviewed: P07451)

Alternative names: Carbonate dehydratase III, Carbonic anhydrase III

All UniProt accessions (3): E5RHI4, P07451, V9HWA3

UniProt curated annotations — full annotation on UniProt →

Function. Reversible hydration of carbon dioxide.

Subcellular location. Cytoplasm.

Tissue specificity. Muscle specific.

Post-translational modifications. S-thiolated both by thiol-disulfide exchange with glutathione disulfide and by oxyradical-initiated S-thiolation with reduced glutathione. S-glutathionylated in hepatocytes under oxidative stress.

Activity regulation. Activated by proton donors such as imidazole and the dipeptide histidylhistidine. Inhibited by coumarins and sulfonamide derivatives such as acetazolamide.

Similarity. Belongs to the alpha-carbonic anhydrase family.

RefSeq proteins (1): NP_005172* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001148CA_domDomain
IPR018338Carbonic_anhydrase_a-class_CSConserved_site
IPR023561Carbonic_anhydrase_a-classFamily
IPR036398CA_dom_sfHomologous_superfamily

Pfam: PF00194

Enzyme classification (BRENDA):

  • EC 4.2.1.1 — carbonic anhydrase (BRENDA: 178 organisms, 196 substrates, 2137 inhibitors, 263 Km, 291 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
CO20.012–4700194
4-NITROPHENYL ACETATE0.0024–30.5316
H2CO30.434–112.716
HCO3-9.3–374
P-NITROPHENYL ACETATE3.86–6.84
4-NITROPHENYL PHOSPHATE0.935–2.1952
COS1.861
HISTAMINE7.91
CS20

Catalyzed reactions (Rhea), 1 shown:

  • hydrogencarbonate + H(+) = CO2 + H2O (RHEA:10748)

UniProt features (55 total): strand 17, modified residue 14, helix 10, binding site 4, mutagenesis site 3, turn 2, initiator methionine 1, chain 1, domain 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

5 structures.

PDBMethodResolution (Å)
3UYQX-RAY DIFFRACTION1.7
1Z93X-RAY DIFFRACTION2.1
1Z97X-RAY DIFFRACTION2.1
2HFWX-RAY DIFFRACTION2.5
3UYNX-RAY DIFFRACTION2.6

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P07451-F197.990.99

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 94; 96; 119; 198–199

Post-translational modifications (14): 43, 48, 50, 55, 73, 127, 129, 176, 182, 187, 216, 219, 2, 29

Mutagenesis-validated functional residues (3):

PositionPhenotype
64enhanced proton transfer in catalysis.
67enhanced proton transfer in catalysis.
197enhanced activity by at least 10-fold.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-1475029Reversible hydration of carbon dioxide
R-HSA-1430728Metabolism

MSigDB gene sets: 196 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOMF_CARBONATE_DEHYDRATASE_ACTIVITY, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, HUMMERICH_MALIGNANT_SKIN_TUMOR_DN, DARWICHE_SKIN_TUMOR_PROMOTER_UP, GOBP_REGENERATION, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_DN, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, RIZKI_TUMOR_INVASIVENESS_3D_DN

GO Biological Process (14): skeletal muscle contraction (GO:0003009), response to oxidative stress (GO:0006979), positive regulation of cell population proliferation (GO:0008284), response to bacterium (GO:0009617), cellular response to insulin stimulus (GO:0032869), response to lipid (GO:0033993), cellular response to leptin stimulus (GO:0044320), response to ethanol (GO:0045471), cellular response to hypoxia (GO:0071456), liver regeneration (GO:0097421), negative regulation of reactive oxygen species biosynthetic process (GO:1903427), negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide (GO:1903751), negative regulation of apoptotic process (GO:0043066), response to alcohol (GO:0097305)

GO Molecular Function (7): carbonate dehydratase activity (GO:0004089), zinc ion binding (GO:0008270), nickel cation binding (GO:0016151), phosphatase activity (GO:0016791), protein binding (GO:0005515), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), sarcomere (GO:0030017)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Metabolism1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
transition metal ion binding2
striated muscle contraction1
musculoskeletal movement1
response to stress1
cell population proliferation1
regulation of cell population proliferation1
positive regulation of cellular process1
response to other organism1
response to insulin1
cellular response to peptide hormone stimulus1
response to chemical1
cellular response to hormone stimulus1
response to leptin1
response to alcohol1
response to hypoxia1
cellular response to stress1
cellular response to decreased oxygen levels1
liver development1
animal organ regeneration1
negative regulation of biosynthetic process1
reactive oxygen species biosynthetic process1
regulation of reactive oxygen species biosynthetic process1
negative regulation of reactive oxygen species metabolic process1
intrinsic apoptotic signaling pathway in response to hydrogen peroxide1
negative regulation of hydrogen peroxide-mediated programmed cell death1
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway1
regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide1
apoptotic process1
regulation of apoptotic process1
negative regulation of programmed cell death1
response to oxygen-containing compound1
hydro-lyase activity1
phosphoric ester hydrolase activity1
binding1
catalytic activity1
cation binding1
intracellular membrane-bounded organelle1
intracellular anatomical structure1
cytoplasm1

Protein interactions and networks

STRING

1284 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CA3CA4P22748822
CA3CYP24A1Q07973779
CA3SLC2A5P22732764
CA3ENO1P06733656
CA3ALBP02768590
CA3MBP02144586
CA3SPARCP09486494
CA3TGP01266492
CA3FTH1P02794482
CA3RNASE1P07998468
CA3CASP8Q14790455
CA3ENO3P13929439
CA3CALM1P02593433
CA3CKMP06732431
CA3SLC4A4Q9Y6R1416

IntAct

10 interactions, top by confidence:

ABTypeScore
CA3LXNpsi-mi:“MI:0915”(physical association)0.560
CA3HPCAL1psi-mi:“MI:0915”(physical association)0.560
HSD17B10SSBpsi-mi:“MI:0914”(association)0.530
TMEM120ACA3psi-mi:“MI:0915”(physical association)0.400
MECOMATP2A1psi-mi:“MI:0914”(association)0.350
LXNCA3psi-mi:“MI:0915”(physical association)0.000
CA3HPCAL1psi-mi:“MI:0915”(physical association)0.000

BioGRID (9): CA3 (Two-hybrid), CA3 (Two-hybrid), CA3 (Two-hybrid), CA3 (Affinity Capture-MS), CA3 (Affinity Capture-MS), CA3 (Affinity Capture-MS), CA3 (Affinity Capture-MS), CA3 (Affinity Capture-MS), CA3 (Affinity Capture-Luminescence)

ESM2 similar proteins: B0BNN3, O76206, P00441, P00445, P00915, P00916, P00917, P00918, P00919, P00920, P00921, P00922, P07450, P07451, P07452, P07630, P13634, P14141, P16015, P27139, P28755, P35217, P43166, P48282, P48284, P60052, P82205, P83299, Q0IIW3, Q1LZA1, Q27504, Q3SZX4, Q42961, Q5S1S4, Q6C662, Q7M316, Q7M317, Q8HXQ0, Q8HXQ1, Q8HXQ2

Diamond homologs: A0A7H0DN92, A0JN41, B0BNN3, O57211, P00915, P00916, P00917, P00918, P00919, P00920, P00921, P04195, P07450, P07451, P07452, P07630, P0DSY1, P0DSY2, P13634, P14141, P16015, P20508, P23470, P23471, P23589, P27139, P35217, P35218, P43165, P43166, P48282, P48283, P61215, P83299, Q05909, Q1LZA1, Q3SZX4, Q5R4U0, Q5S1S4, Q66HG6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

25 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance20
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

850 predictions. Top by Δscore:

VariantEffectΔscore
8:85438941:ACGGT:Adonor_loss1.0000
8:85438942:CGG:Cdonor_loss1.0000
8:85438944:G:GGdonor_gain1.0000
8:85438945:T:Adonor_loss1.0000
8:85439709:TA:Tacceptor_loss1.0000
8:85439710:A:AGacceptor_gain1.0000
8:85439710:A:ATacceptor_loss1.0000
8:85439711:G:GGacceptor_gain1.0000
8:85439711:G:GTacceptor_loss1.0000
8:85439866:G:GTdonor_gain1.0000
8:85439866:G:Tdonor_gain1.0000
8:85439905:GTCAA:Gdonor_gain1.0000
8:85439906:TC:Tdonor_gain1.0000
8:85439910:G:GGdonor_gain1.0000
8:85442071:A:AGacceptor_gain1.0000
8:85442072:G:GGacceptor_gain1.0000
8:85443593:A:Tdonor_gain1.0000
8:85443597:T:Gdonor_gain1.0000
8:85444024:A:AGacceptor_gain1.0000
8:85444024:AT:Aacceptor_gain1.0000
8:85444024:ATG:Aacceptor_gain1.0000
8:85444025:T:Aacceptor_gain1.0000
8:85444025:T:Gacceptor_gain1.0000
8:85444025:T:TAacceptor_loss1.0000
8:85444026:G:Aacceptor_gain1.0000
8:85444029:TTCAG:Tacceptor_loss1.0000
8:85444030:TCAGC:Tacceptor_loss1.0000
8:85444031:CA:Cacceptor_loss1.0000
8:85444032:A:AGacceptor_gain1.0000
8:85444032:AG:Aacceptor_loss1.0000

AlphaMissense

1716 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
8:85439723:T:AW16R0.992
8:85439723:T:CW16R0.992
8:85439725:G:CW16C0.992
8:85439725:G:TW16C0.992
8:85442129:T:AW97R0.992
8:85442129:T:CW97R0.992
8:85439766:C:AP30H0.991
8:85446256:T:AW208R0.991
8:85446256:T:CW208R0.991
8:85442126:C:GH96D0.989
8:85438922:T:AW5R0.988
8:85438922:T:CW5R0.988
8:85438924:G:CW5C0.988
8:85438924:G:TW5C0.988
8:85442157:A:TE106V0.988
8:85442158:G:CE106D0.988
8:85442158:G:TE106D0.988
8:85448145:T:CF259L0.988
8:85448147:C:AF259L0.988
8:85448147:C:GF259L0.988
8:85442131:G:CW97C0.987
8:85442131:G:TW97C0.987
8:85446217:G:CG195R0.987
8:85448129:G:CR253S0.987
8:85448129:G:TR253S0.987
8:85439865:G:TG63V0.986
8:85442186:G:CA116P0.986
8:85444035:T:CL118P0.985
8:85448104:G:CR245P0.985
8:85439769:T:AV31D0.984

dbSNP variants (sampled 300 via entrez): RS1000139317 (8:85448617 C>A,T), RS1000184320 (8:85440520 C>A,T), RS1000346313 (8:85441299 A>G), RS1000411101 (8:85448048 G>A,C), RS1000590530 (8:85439200 A>G), RS1000706967 (8:85442927 T>C,G), RS1000744616 (8:85446588 G>T), RS1000818472 (8:85446794 C>G), RS1000919432 (8:85438829 A>C,G), RS1001161152 (8:85438455 T>A,C), RS1001275624 (8:85438198 C>G,T), RS1002349080 (8:85444968 A>C), RS1002489418 (8:85445342 A>G), RS1002712201 (8:85446239 G>A), RS1002769042 (8:85443052 T>C)

Disease associations

OMIM: gene MIM:114750 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

StudyTraitp-value
GCST002040_1Blood trace element (Zn levels)6.000000e-12
GCST004605_42Mean corpuscular hemoglobin concentration4.000000e-09
GCST006585_2776Blood protein levels2.000000e-08
GCST008059_149Estimated glomerular filtration rate1.000000e-11
GCST90002387_323Immature fraction of reticulocytes6.000000e-19

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0004528mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095180 (PROTEIN FAMILY), CHEMBL2885 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

34 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,052,761 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL19METHAZOLAMIDE465
CHEMBL20ACETAZOLAMIDE428,768
CHEMBL750ZONISAMIDE416,649
CHEMBL1055CHLORTHALIDONE420,442
CHEMBL112ACETAMINOPHEN4157,242
CHEMBL118CELECOXIB4112,844
CHEMBL1200471PYRITHIONE ZINC424,834
CHEMBL1286LEVETIRACETAM413,997
CHEMBL14060PHENOL41,871,332
CHEMBL18ETHOXZOLAMIDE43,042
CHEMBL218490DORZOLAMIDE410,216
CHEMBL255863NILOTINIB438,627
CHEMBL26SULPIRIDE458,543
CHEMBL325041BORTEZOMIB413,120
CHEMBL406INDAPAMIDE416,097
CHEMBL537HYDROQUINONE4296,240
CHEMBL58323LACOSAMIDE45,692
CHEMBL609TRIENTINE4120,457
CHEMBL6466COUMARIN4202,873
CHEMBL865VALDECOXIB441,681
CHEMBL926DOBUTAMINE4
CHEMBL941IMATINIB4
CHEMBL140CURCUMIN3
CHEMBL145CAFFEIC ACID3
CHEMBL165RESVERATROL3
CHEMBL19612SPERMIDINE3
CHEMBL50QUERCETIN3
CHEMBL508338THIMEROSAL3
CHEMBL574P-TOLUENESULFONAMIDE3
CHEMBL251680COUMAPHOS2

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

27 measured of 33 human assays (53 total across all organisms); most potent 27 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acidEC500.0469 nM
aliphatic sulfamate, 1KI3.7 nM
2-(hydrazinecarbonyl)-3-(2-methylphenyl)-1H-indole-5-sulfonamideKI107 nM
3-(2-bromophenyl)-2-(hydrazinecarbonyl)-1H-indole-5-sulfonamideKI110 nM
Topiramate, 3KI250 nM
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamateIC50300 nM
JFD00715KI328 nM
trichloromethiazide, 6KI345 nM
bis-sulfamate, 3KI378 nM
aliphatic sulfamate, 2KI530 nM
3-(2-fluorophenyl)-2-(hydrazinecarbonyl)-1H-indole-5-sulfonamideKI621 nM
Investigational agent, 5KI810 nM
Investigational agent, 4KI850 nM
bis-sulfamate, 4KI890 nM
BMCL182567 Compound 6bKI2840 nM
[2-(cycloheptylmethyl)-1,1-dioxo–benzothiophen-6-yl] sulfamateKI3600 nM
salicylic acidKI9900 nM
4-chloro-N-(2-methyl-2,3-dihydro-1H-indol-1-yl)-3-sulfamoylbenzamideKD10000 nM
phenolKI10200 nM
3,5-difluorophenolKI38800 nM
7-chloro-2-methyl-3-(2-methylphenyl)-4-oxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamideKI54000 nM
4-chloro-2-[(furan-2-ylmethyl)amino]-5-sulfamoylbenzoic acidIC50125000 nM
4-cyanophenolKI131000 nM
2,5-difluorophenolKI134000 nM
4-aminophenolKI159000 nM
benzene-1,3-diolKI795000 nM
1,2-Dihydroxybenzene, XIKI4e+06 nM

ChEMBL bioactivities

254 potent at pChembl≥5 of 376 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.70Ki0.2nMCHEMBL4552380
9.70Ki0.2nMCHEMBL4460315
9.70Ki0.2nMCHEMBL4434661
9.70Ki0.2nMCHEMBL282157
9.52Ki0.3nMP-CHLOROBENZENESULFONAMIDE
9.10Ki0.8nMACETAZOLAMIDE
8.96Ki1.1nMMETHAZOLAMIDE
8.51Ki3.1nMACETAZOLAMIDE
8.17Kd6.7nMCHEMBL4562296
8.12Kd7.6nMCHEMBL4170792
8.12Kd7.5nMCHEMBL4165570
8.08Kd8.4nMCHEMBL120886
8.02Kd9.6nMCHEMBL4161701
8.00Kd10nMCHEMBL4442511
7.92Kd12nMCHEMBL4578934
7.89Kd13nMCHEMBL4437818
7.85IC5014nMCHEMBL65455
7.80Kd16nMCHEMBL4574321
7.77Kd17nMCHEMBL4165127
7.75IC5018nMCHEMBL423848
7.72Kd19nMCHEMBL4160627
7.70IC5020nMMETHAZOLAMIDE
7.70IC5020nMCHEMBL294799
7.70IC5020nMCHEMBL65604
7.70IC5020nMACETAZOLAMIDE
7.70IC5020nMCHEMBL64055
7.70IC5020nMCHEMBL293684
7.70Kd20nMCHEMBL4517317
7.66Kd22nMCHEMBL4521683
7.62Kd24nMCHEMBL4451500
7.62Kd24nMCHEMBL4466140
7.62Kd24nMCHEMBL4470832
7.57Kd27nMCHEMBL4160149
7.55Kd28nMCHEMBL4566236
7.54Kd29nMCHEMBL4577083
7.52Kd30nMCHEMBL4168966
7.52Kd30nMCHEMBL4160149
7.52Kd30nMCHEMBL4163518
7.52Kd30.3nMCHEMBL4176862
7.52Kd30nMCHEMBL4450545
7.51Kd31nMCHEMBL4172331
7.48Kd33nMCHEMBL2333417
7.48Kd33nMCHEMBL4452277
7.48Kd33nMCHEMBL4468834
7.43IC5037nMCHEMBL303108
7.43Kd37nMCHEMBL4166643
7.43Kd37nMCHEMBL4553519
7.42Kd38nMCHEMBL4170371
7.40Kd40nMCHEMBL4168997
7.38Kd42nMCHEMBL4583164

PubChem BioAssay actives

266 with measured affinity, of 975 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-[1-[(2R)-1-(3-azabicyclo[3.2.2]nonan-3-yl)-3-methyl-1-oxobutan-2-yl]triazol-4-yl]benzenesulfonamide1557414: Inhibition of carbonic anhydrase (unknown origin)ki0.0002uM
(2R)-3-phenyl-2-[4-(4-sulfamoylphenyl)triazol-1-yl]-N-(2-thiophen-3-ylethyl)propanamide1557414: Inhibition of carbonic anhydrase (unknown origin)ki0.0002uM
4-nitrobenzenesulfonamide50173: Compound was evaluated for the inhibition of Carbonic anhydraseki0.0002uM
(2R)-N-benzyl-3-methyl-2-[4-(4-sulfamoylphenyl)triazol-1-yl]butanamide1557414: Inhibition of carbonic anhydrase (unknown origin)ki0.0002uM
4-chlorobenzenesulfonamide50173: Compound was evaluated for the inhibition of Carbonic anhydraseki0.0003uM
Acetazolamide50175: Compound was evaluated for the inhibition of Carbonic anhydrase (Non competitive)ki0.0008uM
N-(3-methyl-5-sulfamoyl-1,3,4-thiadiazol-2-ylidene)acetamide311025: Inhibition of human carbonic anhydrase 3ki0.0011uM
N-benzyl-4-chloro-2-phenylsulfanyl-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0067uM
N-benzyl-2,4-dichloro-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0075uM
2-(benzylamino)-4-chloro-N-(3-hydroxypropyl)-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0076uM
2,4-dichloro-5-sulfamoylbenzoic acid1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0084uM
4-chloro-2-(cyclooctylamino)-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0096uM
N-benzyl-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0100uM
4-chloro-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzoic acid1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0120uM
4-bromo-N-butyl-2-phenylsulfanyl-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0130uM
2,2-dioxo-3,4-dihydro-[1,3,4]thiadiazolo[2,3-c][1,2,4]thiadiazine-7-sulfonamide50185: Evaluated for its activity against carbonic anhydrase (CA) in anesthetized rabbitsic500.0140uM
N-butyl-4-chloro-2-phenylsulfanyl-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0160uM
2,4-dibromo-5-sulfamoylbenzoic acid1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0170uM
6-(2-chloroethyl)-5,7-dioxo-[1,3,4]thiadiazolo[3,2-a][1,3,5]triazine-2-sulfonamide50185: Evaluated for its activity against carbonic anhydrase (CA) in anesthetized rabbitsic500.0180uM
4-chloro-2-(cyclooctylamino)-5-sulfamoylbenzoic acid1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0190uM
2-(benzenesulfonyl)-N-benzyl-4-chloro-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0200uM
2,2,2-trifluoro-N-(3-methyl-5-sulfamoyl-1,3,4-thiadiazol-2-ylidene)acetamide50185: Evaluated for its activity against carbonic anhydrase (CA) in anesthetized rabbitsic500.0200uM
6-ethyl-5,7-dioxo-[1,3,4]thiadiazolo[3,2-a][1,3,5]triazine-2-sulfonamide50185: Evaluated for its activity against carbonic anhydrase (CA) in anesthetized rabbitsic500.0200uM
6-methyl-5,7-dioxo-[1,3,4]thiadiazolo[3,2-a][1,3,5]triazine-2-sulfonamide50185: Evaluated for its activity against carbonic anhydrase (CA) in anesthetized rabbitsic500.0200uM
5,7-dioxo-[1,3,4]thiadiazolo[3,2-a][1,3,5]triazine-2-sulfonamide50185: Evaluated for its activity against carbonic anhydrase (CA) in anesthetized rabbitsic500.0200uM
4-bromo-N-butyl-2-(2-hydroxyethylsulfanyl)-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0220uM
4-chloro-N-(2-methoxyethyl)-2-phenylsulfanyl-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0240uM
N-butyl-4-chloro-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0240uM
N-butyl-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0240uM
N-butyl-2,4-dichloro-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0270uM
2-(benzenesulfinyl)-4-bromo-N-(2-hydroxyethyl)-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0280uM
1-(2,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxylic acid1515316: Binding affinity to recombinant N-terminal His6x-tagged human CA3 (4 to 260 residues) expressed in Escherichia coli BL21(DE3) assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assaykd0.0290uM
2-(benzylamino)-N-butyl-4-chloro-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0300uM
4-chloro-2-cyclohexylsulfanyl-N-(2-hydroxyethyl)-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0300uM
2-(benzylamino)-4-chloro-N-(2-hydroxyethyl)-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0300uM
N-benzyl-2-(benzylamino)-4-chloro-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0303uM
2,4-dichloro-N-(2-hydroxyethyl)-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0310uM
4-bromo-N-butyl-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0330uM
1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxylic acid1515316: Binding affinity to recombinant N-terminal His6x-tagged human CA3 (4 to 260 residues) expressed in Escherichia coli BL21(DE3) assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assaykd0.0330uM
2,3,5,6-tetrafluoro-4-(2-hydroxyethylsulfonyl)benzenesulfonamide1170166: Inhibition of human carbonic anhydrase 3 at pH7 and 37 degC by fluorescent thermal shift assaykd0.0330uM
4-chloro-N-(2-hydroxyethyl)-2-phenylsulfanyl-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0370uM
2,4-dibromo-N-butyl-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0370uM
7-hydroxy-5-oxo-[1,3,4]thiadiazolo[3,2-a]pyrimidine-2-sulfonamide50185: Evaluated for its activity against carbonic anhydrase (CA) in anesthetized rabbitsic500.0370uM
2-(benzylamino)-4-chloro-N-(2-methoxyethyl)-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0380uM
2,4-dibromo-N-(2-hydroxyethyl)-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0400uM
2-(benzenesulfonyl)-N-butyl-4-chloro-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0420uM
2,4-dichloro-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0440uM
N-hydroxy-N-methyl-4-nitrobenzenesulfonamide50173: Compound was evaluated for the inhibition of Carbonic anhydraseki0.0440uM
2,4-dichloro-N-(2-methoxyethyl)-5-sulfamoylbenzamide1520081: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0460uM
4-chloro-2-(cyclohexylamino)-N-(2-methoxyethyl)-5-sulfamoylbenzamide1361383: Binding affinity to recombinant human carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assaykd0.0480uM

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, increases expression, affects expression7
Benzo(a)pyreneaffects methylation, affects cotreatment, affects expression, decreases expression, increases expression5
trichostatin Aaffects cotreatment, increases expression3
Cadmium Chloridedecreases expression, increases abundance, increases expression3
Vorinostatincreases expression, affects cotreatment2
sulfamidochrysoidineaffects binding, decreases activity1
methyleugenoldecreases expression1
benzo(b)fluorantheneaffects cotreatment, affects expression1
bisphenol Adecreases expression1
terbufosincreases methylation1
decamethrinincreases expression1
sodium arseniteaffects expression1
1,2,5,6-dibenzanthraceneaffects cotreatment, affects expression1
hydroquinonedecreases expression1
4-aminophenylarsenoxideaffects binding, decreases reaction1
dibenzo(a,l)pyreneaffects cotreatment, affects expression1
dorzolamideaffects binding, decreases activity1
brinzolamideaffects binding, decreases activity1
valdecoxibaffects binding, decreases activity1
N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamideaffects binding, decreases activity1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
clothianidinincreases expression1
dorsomorphinaffects cotreatment, increases expression1
5-hydroxythalidomideaffects binding1
Celecoxibaffects binding, decreases activity1
Topiramateaffects binding, decreases activity1
Arsenic Trioxideaffects binding, decreases reaction1
Zonisamideaffects binding, decreases activity1
Acetazolamideaffects binding, decreases activity1
Benzolamideaffects binding, decreases activity1

ChEMBL screening assays

119 unique, capped per target: 117 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL3386760BindingInhibition of carbonic anhydrase (unknown origin)Substituted thieno[2,3-b]thiophenes and related congeners: Synthesis, β-glucuronidase inhibition activity, crystal structure, and POM analyses. — Bioorg Med Chem
CHEMBL4187333ADMETBinding affinity to recombinant human N-terminal His6-tagged carbonic anhydrase 3 (4 to 260 residues) expressed in Escherichia coli BL21 (DE3) in presence of ANS by fluorescent thermal shift assayBenzimidazole design, synthesis, and docking to build selective carbonic anhydrase VA inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.