CA5A

gene
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Also known as CA5CAVCAVA

Summary

CA5A (carbonic anhydrase 5A, HGNC:1377) is a protein-coding gene on chromosome 16q24.2, encoding Carbonic anhydrase 5A, mitochondrial (P35218). Mitochondrial carbonic anhydrase that catalyzes the reversible conversion of carbon dioxide to bicarbonate/HCO3. It is a selective cancer dependency (DepMap: 29.6% of cell lines).

Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. CA VA is localized in the mitochondria and expressed primarily in the liver. It may play an important role in ureagenesis and gluconeogenesis. CA5A gene maps to chromosome 16q24.3 and an unprocessed pseudogene has been assigned to 16p12-p11.2.

Source: NCBI Gene 763 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (Definitive, ClinGen)
  • GWAS associations: 5
  • Clinical variants (ClinVar): 245 total — 12 pathogenic, 5 likely-pathogenic
  • Phenotypes (HPO): 30
  • Druggable target: yes — 51 molecules with ChEMBL bioactivity
  • Cancer dependency (DepMap): dependent in 29.6% of screened cell lines
  • MANE Select transcript: NM_001739

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:1377
Approved symbolCA5A
Namecarbonic anhydrase 5A
Location16q24.2
Locus typegene with protein product
StatusApproved
AliasesCA5, CAV, CAVA
Ensembl geneENSG00000174990
Ensembl biotypeprotein_coding
OMIM114761
Entrez763

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000566402, ENST00000568801, ENST00000648022, ENST00000648177, ENST00000649158, ENST00000649794, ENST00000906205, ENST00000906206, ENST00000906207, ENST00000906208, ENST00000906209, ENST00000906210, ENST00000906211, ENST00000906212

RefSeq mRNA: 2 — MANE Select: NM_001739 NM_001367225, NM_001739

CCDS: CCDS10965, CCDS92202

Canonical transcript exons

ENST00000649794 — 7 exons

ExonStartEnd
ENSE000011797108789179987891954
ENSE000012410978790242587902520
ENSE000017281148790478687904904
ENSE000023104438790191287901974
ENSE000035394588792674887926945
ENSE000038350878793630987936529
ENSE000038361918788801387888272

Expression profiles

Bgee: expression breadth broad, 87 present calls, max score 94.56.

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
right lobe of liverUBERON:000111494.56gold quality
liverUBERON:000210793.15gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047386.06gold quality
islet of LangerhansUBERON:000000662.56gold quality
Ammon’s hornUBERON:000195458.22gold quality
C1 segment of cervical spinal cordUBERON:000646956.79gold quality
substantia nigraUBERON:000203856.59gold quality
prefrontal cortexUBERON:000045155.82gold quality
putamenUBERON:000187455.71gold quality
apex of heartUBERON:000209854.84gold quality
hypothalamusUBERON:000189853.86gold quality
cerebral cortexUBERON:000095653.53gold quality
anterior cingulate cortexUBERON:000983553.31gold quality
frontal cortexUBERON:000187053.25gold quality
amygdalaUBERON:000187653.17gold quality
dorsolateral prefrontal cortexUBERON:000983452.84gold quality
temporal lobeUBERON:000187152.82gold quality
monocyteCL:000057652.51gold quality
caudate nucleusUBERON:000187352.30gold quality
primary visual cortexUBERON:000243652.07gold quality
superior frontal gyrusUBERON:000266151.94gold quality
Brodmann (1909) area 9UBERON:001354051.20gold quality
leukocyteCL:000073851.18gold quality
nucleus accumbensUBERON:000188250.55gold quality
right frontal lobeUBERON:000281050.29gold quality
brainUBERON:000095550.05gold quality
metanephros cortexUBERON:001053348.42gold quality
thyroid glandUBERON:000204647.18gold quality
right adrenal gland cortexUBERON:003582747.05gold quality
granulocyteCL:000009446.94silver quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes6.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting CA5A, 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-3667-3P99.9967.171636
HSA-MIR-23A-3P99.9574.243163
HSA-MIR-23B-3P99.9574.243163
HSA-MIR-23C99.9573.923192
HSA-MIR-205-3P99.9269.923165
HSA-MIR-6516-3P99.6568.571238
HSA-MIR-130A-5P99.3370.262623
HSA-MIR-470599.1069.101091
HSA-MIR-6868-3P98.6369.642259
HSA-MIR-427798.3467.171323
HSA-MIR-428998.2666.90810
HSA-MIR-1212698.0964.82637
HSA-MIR-148B-5P97.2966.30992

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 29.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

  • activators enhanced kcat, with no effect on KM, favoring the RDS in the catalytic cycle; the activation pattern of the two mitochondrial isoforms is very different from each other and as compared to those of the cytosolic isoforms hCA I and II. (PMID:17174092)
  • CA5A alterations cause hyperammonemia in early childhood that result in mitochondrial carbonic anhydrase VA deficiency (PMID:24530203)
  • In 10 of 96 patients, mutations in CA5A were identified on both alleles but none in CA5B. Exhibiting decreased enzyme activity or thermal stability, all CAVA mutations were proven to cause disease, whereas the three variants showed no relevant effect (PMID:26913920)
  • Mitochondrial carbonic anhydrase VA and VB: properties and roles in health and disease. (PMID:36464834)

Cross-species orthologs

17 orthologs

OrganismSymbolGene ID
danio_rerioca2ENSDARG00000014488
mus_musculusCar5aENSMUSG00000025317
rattus_norvegicusCar5aENSRNOG00000019098
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), CA3 (ENSG00000164879), CA4 (ENSG00000167434), CA7 (ENSG00000168748), CA5B (ENSG00000169239), CA8 (ENSG00000178538), CA13 (ENSG00000185015)

Protein

Protein identifiers

Carbonic anhydrase 5A, mitochondrialP35218 (reviewed: P35218)

Alternative names: Carbonate dehydratase VA, Carbonic anhydrase VA

All UniProt accessions (4): A0A3B3IRX9, A0A3B3ITA6, A0A3B3ITU9, P35218

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial carbonic anhydrase that catalyzes the reversible conversion of carbon dioxide to bicarbonate/HCO3. Mitochondria are impermeable to HCO3, and thus this intramitochondrial carbonic anhydrase is pivotal in providing HCO3 for multiple mitochondrial enzymes that catalyze the formation of essential metabolites of intermediary metabolism in the urea and Krebs cycles.

Subcellular location. Mitochondrion.

Disease relevance. Hyperammonemia due to carbonic anhydrase VA deficiency (CA5AD) [MIM:615751] An autosomal recessive inborn error of metabolism, clinically characterized by infantile hyperammonemic encephalopathy. Metabolic abnormalities include hypoglycemia, hyperlactatemia, metabolic acidosis and respiratory alkalosis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by L- and D-histidine. Activated by L- and D-phenylalanine. Activated by L-adrenaline. Inhibited by coumarins, sulfonamide derivatives such as acetazolamide and Foscarnet (phosphonoformate trisodium salt). Activated by histamine.

Similarity. Belongs to the alpha-carbonic anhydrase family.

RefSeq proteins (2): NP_001354154, NP_001730* (*=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 (7 total): binding site 3, transit peptide 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P35218-F184.380.76

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 (3): 130; 132; 155

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 0 (showing top):

GO Biological Process (0):

GO Molecular Function (4): carbonate dehydratase activity (GO:0004089), zinc ion binding (GO:0008270), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Metabolism1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
hydro-lyase activity1
transition metal ion binding1
catalytic activity1
cation binding1
intracellular anatomical structure1
cellular anatomical structure1
cytoplasm1
intracellular membrane-bounded organelle1
mitochondrion1
intracellular organelle lumen1

Protein interactions and networks

STRING

1154 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CA5ACYP24A1Q07973841
CA5AALBP02768576
CA5AKRT35Q92764549
CA5ATGP01266523
CA5ARNASE1P07998513
CA5AFTH1P02794492
CA5ACD2P06729490
CA5ANAGSQ8N159478
CA5ACD5P06127453
CA5ACD4P01730449
CA5AATRNO75882436
CA5AHTATIP2Q9BUP3420
CA5APCP11498415
CA5AKSR1Q8IVT5370
CA5AUMODP07911353

IntAct

3 interactions, top by confidence:

ABTypeScore
CA5APITRM1psi-mi:“MI:0915”(physical association)0.400
CA5APMPCApsi-mi:“MI:0914”(association)0.350

BioGRID (8): CA5A (Affinity Capture-Western), LMNA (Affinity Capture-Western), TUBB3 (Affinity Capture-Western), PMPCA (Affinity Capture-MS), SIRT3 (Affinity Capture-MS), CA5A (Affinity Capture-MS), PITRM1 (Affinity Capture-MS), CA5A (Proximity Label-MS)

ESM2 similar proteins: A7MCT6, D3ZAW2, O75808, P07450, P07451, P14141, P16015, P19526, P22748, P23589, P27139, P35218, P35739, P43165, P43166, P48283, P97616, Q14CH1, Q16790, Q3SZX4, Q3UFB7, Q497B8, Q5I0I5, Q5S1S4, Q5VT66, Q66HG6, Q8BNV1, Q8CAK1, Q8N1Q1, Q8N371, Q8NF37, Q8NI29, Q8VHB5, Q91W78, Q920N2, Q95323, Q96EN8, Q99N23, Q9CW42, Q9CXT6

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

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

ClassificationCount (floor)
Pathogenic12
Likely pathogenic5
Uncertain significance114
Likely benign85
Benign10

Top pathogenic / likely-pathogenic (17)

Variant IDHGVSClassification
1069842NC_000016.9:g.(?87938372)(87960571_?)delPathogenic
127089NM_001739.2(CA5A):c.619-3421_774+502delPathogenic
1457965NC_000016.9:g.(?87960334)(87970056_?)delPathogenic
1956686NM_001739.2(CA5A):c.683G>A (p.Trp228Ter)Pathogenic
2631113NM_001739.2(CA5A):c.475T>C (p.Trp159Arg)Pathogenic
3243526NC_000016.9:g.(?87969895)(87970056_?)delPathogenic
3336515NC_000016.9:g.(?87921618)(87938511_87960353)delPathogenic
3645507NM_001739.2(CA5A):c.419dup (p.Ser141fs)Pathogenic
570252NM_001739.2(CA5A):c.94C>T (p.Arg32Ter)Pathogenic
813300GRCh37/hg19 16q24.2(chr16:87969915-87970056)Pathogenic
832363NC_000016.10:g.(?87888109)(87891974_?)delPathogenic
832389NC_000016.10:g.(?87904766)(87904924_?)delPathogenic
1705233NC_000016.9:g.(87925561_87935517)(87970113?)delLikely pathogenic
2424226NC_000016.9:g.(?87935498)(87938530_?)dupLikely pathogenic
2503796NM_001739.2(CA5A):c.618+1G>TLikely pathogenic
3670993NM_001739.2(CA5A):c.459+1G>CLikely pathogenic
973554NM_001739.2(CA5A):c.580C>T (p.Gln194Ter)Likely pathogenic

SpliceAI

2210 predictions. Top by Δscore:

VariantEffectΔscore
16:87891793:GCTCA:Gdonor_loss1.0000
16:87891794:CTCA:Cdonor_loss1.0000
16:87891795:TCA:Tdonor_loss1.0000
16:87891796:CA:Cdonor_loss1.0000
16:87891797:A:AGdonor_loss1.0000
16:87891798:CCTGG:Cdonor_gain1.0000
16:87891964:C:CTacceptor_gain1.0000
16:87891965:G:Tacceptor_gain1.0000
16:87901906:GCTTA:Gdonor_loss1.0000
16:87901907:CTTAC:Cdonor_loss1.0000
16:87901908:TTACC:Tdonor_loss1.0000
16:87901909:TAC:Tdonor_loss1.0000
16:87901910:A:Tdonor_loss1.0000
16:87901911:C:Gdonor_loss1.0000
16:87901970:CCGAG:Cacceptor_gain1.0000
16:87901971:CGAG:Cacceptor_gain1.0000
16:87901971:CGAGC:Cacceptor_gain1.0000
16:87901974:GC:Gacceptor_loss1.0000
16:87901975:C:CCacceptor_gain1.0000
16:87901975:CTGC:Cacceptor_loss1.0000
16:87901976:T:Gacceptor_loss1.0000
16:87926743:CTCA:Cdonor_loss1.0000
16:87926744:TCAC:Tdonor_loss1.0000
16:87926746:A:ACdonor_gain1.0000
16:87926746:ACCT:Adonor_loss1.0000
16:87926747:C:CCdonor_gain1.0000
16:87926941:GTGCA:Gacceptor_gain1.0000
16:87926942:TGCA:Tacceptor_gain1.0000
16:87926943:GCA:Gacceptor_gain1.0000
16:87926943:GCAC:Gacceptor_loss1.0000

AlphaMissense

1990 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
16:87904851:G:CH132D0.979
16:87891840:A:GW245R0.978
16:87891840:A:TW245R0.978
16:87926797:G:CN97K0.977
16:87926797:G:TN97K0.977
16:87904816:G:CH143Q0.969
16:87904816:G:TH143Q0.969
16:87904848:A:GW133R0.968
16:87904848:A:TW133R0.968
16:87888159:G:CF296L0.966
16:87888159:G:TF296L0.966
16:87888161:A:GF296L0.966
16:87904791:C:GA152P0.965
16:87926770:A:CF106L0.964
16:87926770:A:TF106L0.964
16:87926772:A:GF106L0.964
16:87904786:C:AE153D0.963
16:87904786:C:GE153D0.963
16:87926882:A:GI69T0.963
16:87888203:G:TR282S0.961
16:87904819:C:AE142D0.961
16:87904819:C:GE142D0.961
16:87902447:G:TA178D0.959
16:87902508:G:CH158D0.959
16:87902517:G:CH155D0.958
16:87902519:A:GL154P0.957
16:87904846:C:AW133C0.957
16:87904846:C:GW133C0.957
16:87926798:T:GN97T0.954
16:87926882:A:CI69S0.953

dbSNP variants (sampled 300 via entrez): RS1000043888 (16:87916092 C>G,T), RS1000053339 (16:87906867 A>G), RS1000066563 (16:87930081 T>C), RS1000079431 (16:87903251 T>C), RS1000079649 (16:87924626 G>A), RS1000135446 (16:87922644 G>A,T), RS1000204245 (16:87895766 A>G), RS1000278817 (16:87913901 G>A), RS1000279870 (16:87906571 G>C), RS1000534756 (16:87924429 C>T), RS1000604401 (16:87929295 T>C), RS1000643225 (16:87916884 C>A,G,T), RS1000684302 (16:87919590 A>T), RS1000740760 (16:87923363 T>C), RS1000745449 (16:87936181 A>C)

Disease associations

OMIM: gene MIM:114761 | disease phenotypes: MIM:615751

GenCC curated gene-disease

DiseaseClassificationInheritance
hyperammonemic encephalopathy due to carbonic anhydrase VA deficiencyDefinitiveAutosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

DiseaseClassificationInheritance
hyperammonemic encephalopathy due to carbonic anhydrase VA deficiencyDefinitiveAR

Mondo (1): hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (MONDO:0014332)

Orphanet (1): Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (Orphanet:401948)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0000952Jaundice
HP:0001254Lethargy
HP:0001263Global developmental delay
HP:0001298Encephalopathy
HP:0001942Metabolic acidosis
HP:0001943Hypoglycemia
HP:0001950Respiratory alkalosis
HP:0001987Hyperammonemia
HP:0001993Ketoacidosis
HP:0002151Increased circulating lactate concentration
HP:0002572Episodic vomiting
HP:0002789Tachypnea
HP:0002919Ketonuria
HP:0003128Lactic acidosis
HP:0003217Hyperglutaminemia
HP:0003228Hypernatremia
HP:0003348Hyperalaninemia
HP:0003572Low plasma citrulline
HP:0003623Neonatal onset
HP:0003648Lacticaciduria
HP:0005961Hypoargininemia
HP:0008358Hyperprolinemia
HP:0011463Childhood onset
HP:00331113-hydroxyisovaleric aciduria
HP:0033213Elevated urine suberic acid level
HP:0033407Elevated urine acetoacetic acid level
HP:0040155Elevated urinary 3-hydroxybutyric acid
HP:0500163Hypoornithinemia
HP:0500251Abnormal urine sebacic acid concentration

GWAS associations

5 associations (top):

StudyTraitp-value
GCST004618_40White blood cell count (basophil)2.000000e-10
GCST004631_28Basophil percentage of white cells1.000000e-12
GCST004634_44Basophil percentage of granulocytes9.000000e-13
GCST009391_1408Metabolite levels6.000000e-06
GCST009391_683Metabolite levels2.000000e-06

EFO canonical traits (5, from GWAS)

EFO IDTrait name
EFO:0005090basophil count
EFO:0007992basophil percentage of leukocytes
EFO:0007995basophil percentage of granulocytes
EFO:00051325-HIAA measurement
EFO:0008529kynurenine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2095180 (PROTEIN FAMILY), CHEMBL2111457 (PROTEIN FAMILY), CHEMBL4789 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

51 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 678,975 (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
CHEMBL18ETHOXZOLAMIDE43,042
CHEMBL220492TOPIRAMATE435,160
CHEMBL1054TRICHLORMETHIAZIDE411,619
CHEMBL1055CHLORTHALIDONE420,442
CHEMBL1096882FLUDARABINE PHOSPHATE4120,716
CHEMBL118CELECOXIB4112,844
CHEMBL1200471PYRITHIONE ZINC424,834
CHEMBL1201754RUFINAMIDE43,052
CHEMBL1286LEVETIRACETAM413,997
CHEMBL1289601LENVATINIB48,784
CHEMBL17DICHLORPHENAMIDE49,022
CHEMBL21SULFANILAMIDE4153,075
CHEMBL2105581VERALIPRIDE41,165
CHEMBL218490DORZOLAMIDE410,216
CHEMBL220491BRINZOLAMIDE48,355
CHEMBL255863NILOTINIB438,627
CHEMBL26SULPIRIDE458,543
CHEMBL325041BORTEZOMIB4
CHEMBL35FUROSEMIDE4
CHEMBL406INDAPAMIDE4
CHEMBL419MAFENIDE4
CHEMBL467HYDROXYUREA4
CHEMBL537HYDROQUINONE4
CHEMBL58323LACOSAMIDE4
CHEMBL609TRIENTINE4
CHEMBL6466COUMARIN4
CHEMBL865VALDECOXIB4

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Carbonic anhydrases

Binding affinities (BindingDB)

49 measured of 59 human assays (103 total across all organisms); most potent 49 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acidEC500.0469 nM
(4S)-4-(ethylamino)-2-(3-methoxypropyl)-1,1-dioxo-2H,3H,4H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamideKI3 nM
aliphatic sulfamate, 1KI3.7 nM
cid_694792KI60 nM
sulfonamide deriv., 7cKI60 nM
sulfonamide deriv., 5aKI61 nM
sulfonamide deriv., 7eKI61 nM
sulfonamide deriv., 8KI63 nM
sulfonamide deriv., 7dKI67 nM
sulfonamide deriv., 5fKI68 nM
sulfonamide deriv., 7hKI71 nM
sulfonamide deriv., 6KI72 nM
sulfonamide deriv., 7iKI73 nM
sulfonamide deriv., 7bKI75 nM
sulfonamide deriv., 7gKI75 nM
sulfonamide deriv., 5cKI77 nM
sulfonamide deriv., 5dKI84 nM
2-(hydrazinecarbonyl)-3-(2-methylphenyl)-1H-indole-5-sulfonamideKI107 nM
sulfonamide deriv., 7aKI108 nM
3-(2-bromophenyl)-2-(hydrazinecarbonyl)-1H-indole-5-sulfonamideKI110 nM
sulfonamide deriv., 5bKI161 nM
Topiramate, 3KI250 nM
sulfonamide deriv., 7fKI263 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
1,3,4-Thiadiazole-2-sulfonamide, 6IC502700 nM
BMCL182567 Compound 6bKI2840 nM
amino-N-{[(1R,2S,6S,9R)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.0^{2,6}]dodecan-6-yl]methyl}sulfonamideKI3450 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
4-methylbenzene-1-sulfonamideIC5022100 nM
3,5-difluorophenolKI38800 nM
Dorzolamide, DZAKI50000 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

915 potent at pChembl≥5 of 988 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
11.00Ki0.01nMCYANIDE
10.70Ki0.02nMHYDROGEN SULFIDE
10.70Kd0.02nMCHEMBL4205449
10.22Kd0.06nMCHEMBL4207063
10.15Kd0.07nMCHEMBL4214894
9.96Kd0.11nMCHEMBL4474833
9.92Ki0.12nMSULFAMATE
9.85Kd0.14nMCHEMBL4210750
9.85Kd0.14nMCHEMBL4204729
9.70Ki0.2nMCHEMBL4552380
9.70Ki0.2nMCHEMBL4460315
9.70Ki0.2nMCHEMBL4434661
9.70Ki0.2nMCHEMBL282157
9.60Kd0.25nMCHEMBL1272187
9.52Ki0.3nMCHEMBL186537
9.52Ki0.3nMP-CHLOROBENZENESULFONAMIDE
9.46Kd0.35nMCHEMBL4474251
9.34Kd0.46nMCHEMBL4439909
9.33Kd0.47nMCHEMBL4207242
9.18Kd0.66nMCHEMBL4207577
9.12Kd0.75nMCHEMBL4451503
9.11Kd0.77nMCHEMBL4205044
9.10Kd0.8nMCHEMBL4218335
9.10Ki0.8nMACETAZOLAMIDE
9.08Ki0.84nMSULFAMIDE
9.06Kd0.88nMCHEMBL4211504
9.04Kd0.92nMCHEMBL4450456
8.96Kd1.1nMCHEMBL4449430
8.96Kd1.1nMCHEMBL4466140
8.96Kd1.1nMCHEMBL4442511
8.80Kd1.6nMCHEMBL4588838
8.80Kd1.6nMCHEMBL4513684
8.77Kd1.7nMCHEMBL4444201
8.74Ki1.8nMACETAZOLAMIDE
8.74Kd1.82nMCHEMBL4207063
8.70Ki2nMETHOXZOLAMIDE
8.70Kd2nMCHEMBL4515586
8.69Kd2.04nMCHEMBL4205449
8.68Kd2.1nMCHEMBL4565224
8.66Kd2.2nMCHEMBL4456851
8.60Ki2.5nMMETHAZOLAMIDE
8.59Kd2.6nMCHEMBL4451500
8.55Kd2.8nMCHEMBL4572161
8.54Ki2.9nMCHEMBL4171921
8.52Kd3nMCHEMBL4468310
8.46Kd3.46nMCHEMBL1272188
8.46Kd3.5nMCHEMBL4468834
8.46Ki3.49nMCHEMBL120886
8.44Kd3.6nMCHEMBL4475073
8.41Kd3.9nMCHEMBL4450545

PubChem BioAssay actives

991 with measured affinity, of 1560 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
2-chloro-5-[2-(5,6-dimethylbenzimidazol-1-yl)acetyl]benzenesulfonamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd<0.0001uM
N-(benzimidazol-1-yl)-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd<0.0001uM
sulfane238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coliki<0.0001uM
5-[2-(benzimidazol-1-yl)acetyl]-2-chlorobenzenesulfonamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd<0.0001uM
Hydrogen Cyanide238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coliki<0.0001uM
5-[2-(benzimidazol-1-yl)acetyl]-2,4-dichlorobenzenesulfonamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd0.0001uM
5-[2-(benzimidazol-1-yl)acetyl]-2-chloro-4-(2-phenylethylsulfanyl)benzenesulfonamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd0.0001uM
2-chloro-5-(2-imidazol-1-ylacetyl)benzenesulfonamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd0.0001uM
2,4-dichloro-5-[2-(5,6-dimethylbenzimidazol-1-yl)acetyl]benzenesulfonamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd0.0001uM
N-[(E)-benzylideneamino]-1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxamide1515318: Binding affinity to recombinant full length C-terminal His6x-tagged human CA5A expressed in Escherichia coli BL21(DE3) assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assaykd0.0001uM
sulfamic acid238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coliki0.0001uM
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
N-[(E)-benzylideneamino]-5-oxo-1-(4-sulfamoylphenyl)pyrrolidine-3-carboxamide1515318: Binding affinity to recombinant full length C-terminal His6x-tagged human CA5A expressed in Escherichia coli BL21(DE3) assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assaykd0.0003uM
24530238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coliki0.0003uM
4-chlorobenzenesulfonamide50173: Compound was evaluated for the inhibition of Carbonic anhydraseki0.0003uM
2-chloro-5-[2-(5,6-dimethylbenzimidazol-1-yl)acetyl]-4-phenylsulfanylbenzenesulfonamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd0.0005uM
1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxylic acid1515318: Binding affinity to recombinant full length C-terminal His6x-tagged human CA5A expressed in Escherichia coli BL21(DE3) assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assaykd0.0005uM
N-(benzimidazol-1-yl)-2,4-dichloro-5-sulfamoylbenzamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd0.0007uM
2-benzylsulfanyl-4-chloro-N-cyclohexyl-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0008uM
N-(benzimidazol-1-yl)-4-chloro-2-phenylsulfanyl-5-sulfamoylbenzamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd0.0008uM
Acetazolamide50175: Compound was evaluated for the inhibition of Carbonic anhydrase (Non competitive)ki0.0008uM
sulfamide238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coliki0.0008uM
4-chloro-2-cyclohexylsulfanyl-N-(2-methoxyethyl)-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0009uM
2,4-dichloro-5-(2-imidazol-1-ylacetyl)benzenesulfonamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd0.0009uM
N-butyl-4-chloro-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0011uM
N-benzyl-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0011uM
4-[4-(hydrazinecarbonyl)-2-oxopyrrolidin-1-yl]-2,6-dimethylbenzenesulfonamide1515318: Binding affinity to recombinant full length C-terminal His6x-tagged human CA5A expressed in Escherichia coli BL21(DE3) assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assaykd0.0011uM
methyl 4-[(4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzoyl)amino]butanoate1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0016uM
4-[(4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzoyl)amino]butanoic acid1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0016uM
2-benzylsulfanyl-N-butyl-4-chloro-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0017uM
4-bromo-N-(2-hydroxyethyl)-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0020uM
6-ethoxy-1,3-benzothiazole-2-sulfonamide239287: Mean inhibitory constant towards human carbonic anhydrase V determined by spectrophotometric dansylamide binding assayki0.0020uM
2-benzylsulfanyl-4-chloro-N-(2-hydroxyethyl)-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0021uM
4-chloro-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0022uM
N-(3-methyl-5-sulfamoyl-1,3,4-thiadiazol-2-ylidene)acetamide239287: Mean inhibitory constant towards human carbonic anhydrase V determined by spectrophotometric dansylamide binding assayki0.0025uM
N-butyl-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0026uM
methyl 4-[(2-benzylsulfanyl-4-chloro-5-sulfamoylbenzoyl)amino]butanoate1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0028uM
4-pentylselanylbenzenesulfonamide1354956: Inhibition of human carbonic anhydrase 5A after 15 mins by stopped flow carbon dioxide hydration assayki0.0029uM
2-benzylsulfanyl-4-bromo-N-(2-hydroxyethyl)-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0030uM
4-bromo-N-butyl-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0035uM
2-chloro-5-[2-(2-methylbenzimidazol-1-yl)acetyl]benzenesulfonamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd0.0035uM
4-chloro-2-cyclohexylsulfanyl-N-(3-hydroxypropyl)-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0036uM
4-chloro-2-cyclohexylsulfanyl-N-(2-hydroxyethyl)-5-sulfamoylbenzamide1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assaykd0.0039uM
4-(2-methoxyethylselanyl)benzenesulfonamide1354956: Inhibition of human carbonic anhydrase 5A after 15 mins by stopped flow carbon dioxide hydration assayki0.0040uM
2-chloro-5-[2-(3,4-dihydro-2H-quinolin-1-yl)acetyl]benzenesulfonamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd0.0042uM
phenylboronic acid238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coliki0.0045uM
2-chloro-5-[2-(2-ethylimidazol-1-yl)acetyl]benzenesulfonamide1373180: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assaykd0.0047uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Aflatoxin B1increases methylation, affects expression, decreases expression4
Acetaminophendecreases expression2
Benzo(a)pyreneaffects methylation, decreases expression2
sulfamic aciddecreases activity1
oryzalinaffects binding, decreases activity1
sodium arsenitedecreases expression1
butyraldehydedecreases expression1
chloric aciddecreases activity1
sodium metasilicatedecreases activity1
benzo(e)pyrenedecreases methylation1
potassium periodatedecreases activity1
molybdatedecreases activity1
tungstatedecreases activity1
K 7174decreases expression1
perchloratedecreases activity1
Rosiglitazonedecreases expression1
Acetazolamideaffects binding, decreases activity1
Bromatesdecreases activity1
Carbonatesdecreases activity1
Diethylnitrosaminedecreases expression1
Dimethyl Sulfoxideincreases expression1
Iodatesdecreases activity1
Methapyrilenedecreases methylation1
Pesticidesaffects methylation1
Thiramincreases expression1
Tretinoindecreases expression1
Valproic Aciddecreases expression1
Vanadatesdecreases activity1
Zincdecreases expression1
Propofoldecreases expression1

ChEMBL screening assays

144 unique, capped per target: 143 binding, 1 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
CHEMBL4406726ADMETInhibition of human recombinant carbonic anhydrase 5A preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assayPhenyl(thio)phosphon(amid)ate Benzenesulfonamides as Potent and Selective Inhibitors of Human Carbonic Anhydrases II and VII Counteract Allodynia in a Mouse Model of Oxaliplatin-Induced Neuropathy. — J Med Chem

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT03655223Not specifiedENROLLING_BY_INVITATIONEarly Check: Expanded Screening in Newborns