CA5A
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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
| Field | Value |
|---|---|
| HGNC ID | HGNC:1377 |
| Approved symbol | CA5A |
| Name | carbonic anhydrase 5A |
| Location | 16q24.2 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | CA5, CAV, CAVA |
| Ensembl gene | ENSG00000174990 |
| Ensembl biotype | protein_coding |
| OMIM | 114761 |
| Entrez | 763 |
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
| Exon | Start | End |
|---|---|---|
| ENSE00001179710 | 87891799 | 87891954 |
| ENSE00001241097 | 87902425 | 87902520 |
| ENSE00001728114 | 87904786 | 87904904 |
| ENSE00002310443 | 87901912 | 87901974 |
| ENSE00003539458 | 87926748 | 87926945 |
| ENSE00003835087 | 87936309 | 87936529 |
| ENSE00003836191 | 87888013 | 87888272 |
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):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| right lobe of liver | UBERON:0001114 | 94.56 | gold quality |
| liver | UBERON:0002107 | 93.15 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 86.06 | gold quality |
| islet of Langerhans | UBERON:0000006 | 62.56 | gold quality |
| Ammon’s horn | UBERON:0001954 | 58.22 | gold quality |
| C1 segment of cervical spinal cord | UBERON:0006469 | 56.79 | gold quality |
| substantia nigra | UBERON:0002038 | 56.59 | gold quality |
| prefrontal cortex | UBERON:0000451 | 55.82 | gold quality |
| putamen | UBERON:0001874 | 55.71 | gold quality |
| apex of heart | UBERON:0002098 | 54.84 | gold quality |
| hypothalamus | UBERON:0001898 | 53.86 | gold quality |
| cerebral cortex | UBERON:0000956 | 53.53 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 53.31 | gold quality |
| frontal cortex | UBERON:0001870 | 53.25 | gold quality |
| amygdala | UBERON:0001876 | 53.17 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 52.84 | gold quality |
| temporal lobe | UBERON:0001871 | 52.82 | gold quality |
| monocyte | CL:0000576 | 52.51 | gold quality |
| caudate nucleus | UBERON:0001873 | 52.30 | gold quality |
| primary visual cortex | UBERON:0002436 | 52.07 | gold quality |
| superior frontal gyrus | UBERON:0002661 | 51.94 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 51.20 | gold quality |
| leukocyte | CL:0000738 | 51.18 | gold quality |
| nucleus accumbens | UBERON:0001882 | 50.55 | gold quality |
| right frontal lobe | UBERON:0002810 | 50.29 | gold quality |
| brain | UBERON:0000955 | 50.05 | gold quality |
| metanephros cortex | UBERON:0010533 | 48.42 | gold quality |
| thyroid gland | UBERON:0002046 | 47.18 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 47.05 | gold quality |
| granulocyte | CL:0000094 | 46.94 | silver quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 6.31 |
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):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-3667-3P | 99.99 | 67.17 | 1636 |
| HSA-MIR-23A-3P | 99.95 | 74.24 | 3163 |
| HSA-MIR-23B-3P | 99.95 | 74.24 | 3163 |
| HSA-MIR-23C | 99.95 | 73.92 | 3192 |
| HSA-MIR-205-3P | 99.92 | 69.92 | 3165 |
| HSA-MIR-6516-3P | 99.65 | 68.57 | 1238 |
| HSA-MIR-130A-5P | 99.33 | 70.26 | 2623 |
| HSA-MIR-4705 | 99.10 | 69.10 | 1091 |
| HSA-MIR-6868-3P | 98.63 | 69.64 | 2259 |
| HSA-MIR-4277 | 98.34 | 67.17 | 1323 |
| HSA-MIR-4289 | 98.26 | 66.90 | 810 |
| HSA-MIR-12126 | 98.09 | 64.82 | 637 |
| HSA-MIR-148B-5P | 97.29 | 66.30 | 992 |
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
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | ca2 | ENSDARG00000014488 |
| mus_musculus | Car5a | ENSMUSG00000025317 |
| rattus_norvegicus | Car5a | ENSRNOG00000019098 |
| drosophila_melanogaster | CAH13 | FBGN0033542 |
| drosophila_melanogaster | CAH14 | FBGN0034554 |
| drosophila_melanogaster | CAH15 | FBGN0034560 |
| drosophila_melanogaster | CAH7 | FBGN0037788 |
| drosophila_melanogaster | CAH8 | FBGN0038956 |
| drosophila_melanogaster | CAH4 | FBGN0039235 |
| drosophila_melanogaster | CAH9 | FBGN0039486 |
| drosophila_melanogaster | CAH6 | FBGN0039838 |
| drosophila_melanogaster | CAH16 | FBGN0040628 |
| drosophila_melanogaster | CAH5 | FBGN0040629 |
| drosophila_melanogaster | CARPB | FBGN0052698 |
| caenorhabditis_elegans | WBGENE00000279 | |
| caenorhabditis_elegans | WBGENE00000283 | |
| caenorhabditis_elegans | cah-6 | WBGENE00000284 |
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, mitochondrial — P35218 (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)
| ID | Name | Type |
|---|---|---|
| IPR001148 | CA_dom | Domain |
| IPR018338 | Carbonic_anhydrase_a-class_CS | Conserved_site |
| IPR023561 | Carbonic_anhydrase_a-class | Family |
| IPR036398 | CA_dom_sf | Homologous_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.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| CO2 | 0.012–4700 | 194 |
| 4-NITROPHENYL ACETATE | 0.0024–30.53 | 16 |
| H2CO3 | 0.434–112.7 | 16 |
| HCO3- | 9.3–37 | 4 |
| P-NITROPHENYL ACETATE | 3.86–6.8 | 4 |
| 4-NITROPHENYL PHOSPHATE | 0.935–2.195 | 2 |
| COS | 1.86 | 1 |
| HISTAMINE | 7.9 | 1 |
| CS2 | — | 0 |
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)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P35218-F1 | 84.38 | 0.76 |
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
| ID | Pathway |
|---|---|
| R-HSA-1475029 | Reversible hydration of carbon dioxide |
| R-HSA-1430728 | Metabolism |
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:
| Category | Pathways |
|---|---|
| Metabolism | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| hydro-lyase activity | 1 |
| transition metal ion binding | 1 |
| catalytic activity | 1 |
| cation binding | 1 |
| intracellular anatomical structure | 1 |
| cellular anatomical structure | 1 |
| cytoplasm | 1 |
| intracellular membrane-bounded organelle | 1 |
| mitochondrion | 1 |
| intracellular organelle lumen | 1 |
Protein interactions and networks
STRING
1154 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| CA5A | CYP24A1 | Q07973 | 841 |
| CA5A | ALB | P02768 | 576 |
| CA5A | KRT35 | Q92764 | 549 |
| CA5A | TG | P01266 | 523 |
| CA5A | RNASE1 | P07998 | 513 |
| CA5A | FTH1 | P02794 | 492 |
| CA5A | CD2 | P06729 | 490 |
| CA5A | NAGS | Q8N159 | 478 |
| CA5A | CD5 | P06127 | 453 |
| CA5A | CD4 | P01730 | 449 |
| CA5A | ATRN | O75882 | 436 |
| CA5A | HTATIP2 | Q9BUP3 | 420 |
| CA5A | PC | P11498 | 415 |
| CA5A | KSR1 | Q8IVT5 | 370 |
| CA5A | UMOD | P07911 | 353 |
IntAct
3 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| CA5A | PITRM1 | psi-mi:“MI:0915”(physical association) | 0.400 |
| CA5A | PMPCA | psi-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):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 12 |
| Likely pathogenic | 5 |
| Uncertain significance | 114 |
| Likely benign | 85 |
| Benign | 10 |
Top pathogenic / likely-pathogenic (17)
| Variant ID | HGVS | Classification |
|---|---|---|
| 1069842 | NC_000016.9:g.(?87938372)(87960571_?)del | Pathogenic |
| 127089 | NM_001739.2(CA5A):c.619-3421_774+502del | Pathogenic |
| 1457965 | NC_000016.9:g.(?87960334)(87970056_?)del | Pathogenic |
| 1956686 | NM_001739.2(CA5A):c.683G>A (p.Trp228Ter) | Pathogenic |
| 2631113 | NM_001739.2(CA5A):c.475T>C (p.Trp159Arg) | Pathogenic |
| 3243526 | NC_000016.9:g.(?87969895)(87970056_?)del | Pathogenic |
| 3336515 | NC_000016.9:g.(?87921618)(87938511_87960353)del | Pathogenic |
| 3645507 | NM_001739.2(CA5A):c.419dup (p.Ser141fs) | Pathogenic |
| 570252 | NM_001739.2(CA5A):c.94C>T (p.Arg32Ter) | Pathogenic |
| 813300 | GRCh37/hg19 16q24.2(chr16:87969915-87970056) | Pathogenic |
| 832363 | NC_000016.10:g.(?87888109)(87891974_?)del | Pathogenic |
| 832389 | NC_000016.10:g.(?87904766)(87904924_?)del | Pathogenic |
| 1705233 | NC_000016.9:g.(87925561_87935517)(87970113?)del | Likely pathogenic |
| 2424226 | NC_000016.9:g.(?87935498)(87938530_?)dup | Likely pathogenic |
| 2503796 | NM_001739.2(CA5A):c.618+1G>T | Likely pathogenic |
| 3670993 | NM_001739.2(CA5A):c.459+1G>C | Likely pathogenic |
| 973554 | NM_001739.2(CA5A):c.580C>T (p.Gln194Ter) | Likely pathogenic |
SpliceAI
2210 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 16:87891793:GCTCA:G | donor_loss | 1.0000 |
| 16:87891794:CTCA:C | donor_loss | 1.0000 |
| 16:87891795:TCA:T | donor_loss | 1.0000 |
| 16:87891796:CA:C | donor_loss | 1.0000 |
| 16:87891797:A:AG | donor_loss | 1.0000 |
| 16:87891798:CCTGG:C | donor_gain | 1.0000 |
| 16:87891964:C:CT | acceptor_gain | 1.0000 |
| 16:87891965:G:T | acceptor_gain | 1.0000 |
| 16:87901906:GCTTA:G | donor_loss | 1.0000 |
| 16:87901907:CTTAC:C | donor_loss | 1.0000 |
| 16:87901908:TTACC:T | donor_loss | 1.0000 |
| 16:87901909:TAC:T | donor_loss | 1.0000 |
| 16:87901910:A:T | donor_loss | 1.0000 |
| 16:87901911:C:G | donor_loss | 1.0000 |
| 16:87901970:CCGAG:C | acceptor_gain | 1.0000 |
| 16:87901971:CGAG:C | acceptor_gain | 1.0000 |
| 16:87901971:CGAGC:C | acceptor_gain | 1.0000 |
| 16:87901974:GC:G | acceptor_loss | 1.0000 |
| 16:87901975:C:CC | acceptor_gain | 1.0000 |
| 16:87901975:CTGC:C | acceptor_loss | 1.0000 |
| 16:87901976:T:G | acceptor_loss | 1.0000 |
| 16:87926743:CTCA:C | donor_loss | 1.0000 |
| 16:87926744:TCAC:T | donor_loss | 1.0000 |
| 16:87926746:A:AC | donor_gain | 1.0000 |
| 16:87926746:ACCT:A | donor_loss | 1.0000 |
| 16:87926747:C:CC | donor_gain | 1.0000 |
| 16:87926941:GTGCA:G | acceptor_gain | 1.0000 |
| 16:87926942:TGCA:T | acceptor_gain | 1.0000 |
| 16:87926943:GCA:G | acceptor_gain | 1.0000 |
| 16:87926943:GCAC:G | acceptor_loss | 1.0000 |
AlphaMissense
1990 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 16:87904851:G:C | H132D | 0.979 |
| 16:87891840:A:G | W245R | 0.978 |
| 16:87891840:A:T | W245R | 0.978 |
| 16:87926797:G:C | N97K | 0.977 |
| 16:87926797:G:T | N97K | 0.977 |
| 16:87904816:G:C | H143Q | 0.969 |
| 16:87904816:G:T | H143Q | 0.969 |
| 16:87904848:A:G | W133R | 0.968 |
| 16:87904848:A:T | W133R | 0.968 |
| 16:87888159:G:C | F296L | 0.966 |
| 16:87888159:G:T | F296L | 0.966 |
| 16:87888161:A:G | F296L | 0.966 |
| 16:87904791:C:G | A152P | 0.965 |
| 16:87926770:A:C | F106L | 0.964 |
| 16:87926770:A:T | F106L | 0.964 |
| 16:87926772:A:G | F106L | 0.964 |
| 16:87904786:C:A | E153D | 0.963 |
| 16:87904786:C:G | E153D | 0.963 |
| 16:87926882:A:G | I69T | 0.963 |
| 16:87888203:G:T | R282S | 0.961 |
| 16:87904819:C:A | E142D | 0.961 |
| 16:87904819:C:G | E142D | 0.961 |
| 16:87902447:G:T | A178D | 0.959 |
| 16:87902508:G:C | H158D | 0.959 |
| 16:87902517:G:C | H155D | 0.958 |
| 16:87902519:A:G | L154P | 0.957 |
| 16:87904846:C:A | W133C | 0.957 |
| 16:87904846:C:G | W133C | 0.957 |
| 16:87926798:T:G | N97T | 0.954 |
| 16:87926882:A:C | I69S | 0.953 |
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
| Disease | Classification | Inheritance |
|---|---|---|
| hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency | Definitive | Autosomal recessive |
ClinGen Gene-Disease Validity (1)
Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.
| Disease | Classification | Inheritance |
|---|---|---|
| hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency | Definitive | AR |
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):
| HPO | Term |
|---|---|
| HP:0000007 | Autosomal recessive inheritance |
| HP:0000952 | Jaundice |
| HP:0001254 | Lethargy |
| HP:0001263 | Global developmental delay |
| HP:0001298 | Encephalopathy |
| HP:0001942 | Metabolic acidosis |
| HP:0001943 | Hypoglycemia |
| HP:0001950 | Respiratory alkalosis |
| HP:0001987 | Hyperammonemia |
| HP:0001993 | Ketoacidosis |
| HP:0002151 | Increased circulating lactate concentration |
| HP:0002572 | Episodic vomiting |
| HP:0002789 | Tachypnea |
| HP:0002919 | Ketonuria |
| HP:0003128 | Lactic acidosis |
| HP:0003217 | Hyperglutaminemia |
| HP:0003228 | Hypernatremia |
| HP:0003348 | Hyperalaninemia |
| HP:0003572 | Low plasma citrulline |
| HP:0003623 | Neonatal onset |
| HP:0003648 | Lacticaciduria |
| HP:0005961 | Hypoargininemia |
| HP:0008358 | Hyperprolinemia |
| HP:0011463 | Childhood onset |
| HP:0033111 | 3-hydroxyisovaleric aciduria |
| HP:0033213 | Elevated urine suberic acid level |
| HP:0033407 | Elevated urine acetoacetic acid level |
| HP:0040155 | Elevated urinary 3-hydroxybutyric acid |
| HP:0500163 | Hypoornithinemia |
| HP:0500251 | Abnormal urine sebacic acid concentration |
GWAS associations
5 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST004618_40 | White blood cell count (basophil) | 2.000000e-10 |
| GCST004631_28 | Basophil percentage of white cells | 1.000000e-12 |
| GCST004634_44 | Basophil percentage of granulocytes | 9.000000e-13 |
| GCST009391_1408 | Metabolite levels | 6.000000e-06 |
| GCST009391_683 | Metabolite levels | 2.000000e-06 |
EFO canonical traits (5, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0005090 | basophil count |
| EFO:0007992 | basophil percentage of leukocytes |
| EFO:0007995 | basophil percentage of granulocytes |
| EFO:0005132 | 5-HIAA measurement |
| EFO:0008529 | kynurenine 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).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL19 | METHAZOLAMIDE | 4 | 65 |
| CHEMBL20 | ACETAZOLAMIDE | 4 | 28,768 |
| CHEMBL750 | ZONISAMIDE | 4 | 16,649 |
| CHEMBL18 | ETHOXZOLAMIDE | 4 | 3,042 |
| CHEMBL220492 | TOPIRAMATE | 4 | 35,160 |
| CHEMBL1054 | TRICHLORMETHIAZIDE | 4 | 11,619 |
| CHEMBL1055 | CHLORTHALIDONE | 4 | 20,442 |
| CHEMBL1096882 | FLUDARABINE PHOSPHATE | 4 | 120,716 |
| CHEMBL118 | CELECOXIB | 4 | 112,844 |
| CHEMBL1200471 | PYRITHIONE ZINC | 4 | 24,834 |
| CHEMBL1201754 | RUFINAMIDE | 4 | 3,052 |
| CHEMBL1286 | LEVETIRACETAM | 4 | 13,997 |
| CHEMBL1289601 | LENVATINIB | 4 | 8,784 |
| CHEMBL17 | DICHLORPHENAMIDE | 4 | 9,022 |
| CHEMBL21 | SULFANILAMIDE | 4 | 153,075 |
| CHEMBL2105581 | VERALIPRIDE | 4 | 1,165 |
| CHEMBL218490 | DORZOLAMIDE | 4 | 10,216 |
| CHEMBL220491 | BRINZOLAMIDE | 4 | 8,355 |
| CHEMBL255863 | NILOTINIB | 4 | 38,627 |
| CHEMBL26 | SULPIRIDE | 4 | 58,543 |
| CHEMBL325041 | BORTEZOMIB | 4 | |
| CHEMBL35 | FUROSEMIDE | 4 | |
| CHEMBL406 | INDAPAMIDE | 4 | |
| CHEMBL419 | MAFENIDE | 4 | |
| CHEMBL467 | HYDROXYUREA | 4 | |
| CHEMBL537 | HYDROQUINONE | 4 | |
| CHEMBL58323 | LACOSAMIDE | 4 | |
| CHEMBL609 | TRIENTINE | 4 | |
| CHEMBL6466 | COUMARIN | 4 | |
| CHEMBL865 | VALDECOXIB | 4 |
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.
| Ligand | Measure | Value |
|---|---|---|
| 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid | EC50 | 0.0469 nM |
| (4S)-4-(ethylamino)-2-(3-methoxypropyl)-1,1-dioxo-2H,3H,4H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide | KI | 3 nM |
| aliphatic sulfamate, 1 | KI | 3.7 nM |
| cid_694792 | KI | 60 nM |
| sulfonamide deriv., 7c | KI | 60 nM |
| sulfonamide deriv., 5a | KI | 61 nM |
| sulfonamide deriv., 7e | KI | 61 nM |
| sulfonamide deriv., 8 | KI | 63 nM |
| sulfonamide deriv., 7d | KI | 67 nM |
| sulfonamide deriv., 5f | KI | 68 nM |
| sulfonamide deriv., 7h | KI | 71 nM |
| sulfonamide deriv., 6 | KI | 72 nM |
| sulfonamide deriv., 7i | KI | 73 nM |
| sulfonamide deriv., 7b | KI | 75 nM |
| sulfonamide deriv., 7g | KI | 75 nM |
| sulfonamide deriv., 5c | KI | 77 nM |
| sulfonamide deriv., 5d | KI | 84 nM |
| 2-(hydrazinecarbonyl)-3-(2-methylphenyl)-1H-indole-5-sulfonamide | KI | 107 nM |
| sulfonamide deriv., 7a | KI | 108 nM |
| 3-(2-bromophenyl)-2-(hydrazinecarbonyl)-1H-indole-5-sulfonamide | KI | 110 nM |
| sulfonamide deriv., 5b | KI | 161 nM |
| Topiramate, 3 | KI | 250 nM |
| sulfonamide deriv., 7f | KI | 263 nM |
| 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate | IC50 | 300 nM |
| JFD00715 | KI | 328 nM |
| trichloromethiazide, 6 | KI | 345 nM |
| bis-sulfamate, 3 | KI | 378 nM |
| aliphatic sulfamate, 2 | KI | 530 nM |
| 3-(2-fluorophenyl)-2-(hydrazinecarbonyl)-1H-indole-5-sulfonamide | KI | 621 nM |
| Investigational agent, 5 | KI | 810 nM |
| Investigational agent, 4 | KI | 850 nM |
| bis-sulfamate, 4 | KI | 890 nM |
| 1,3,4-Thiadiazole-2-sulfonamide, 6 | IC50 | 2700 nM |
| BMCL182567 Compound 6b | KI | 2840 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}sulfonamide | KI | 3450 nM |
| [2-(cycloheptylmethyl)-1,1-dioxo–benzothiophen-6-yl] sulfamate | KI | 3600 nM |
| salicylic acid | KI | 9900 nM |
| 4-chloro-N-(2-methyl-2,3-dihydro-1H-indol-1-yl)-3-sulfamoylbenzamide | KD | 10000 nM |
| phenol | KI | 10200 nM |
| 4-methylbenzene-1-sulfonamide | IC50 | 22100 nM |
| 3,5-difluorophenol | KI | 38800 nM |
| Dorzolamide, DZA | KI | 50000 nM |
| 7-chloro-2-methyl-3-(2-methylphenyl)-4-oxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide | KI | 54000 nM |
| 4-chloro-2-[(furan-2-ylmethyl)amino]-5-sulfamoylbenzoic acid | IC50 | 125000 nM |
| 4-cyanophenol | KI | 131000 nM |
| 2,5-difluorophenol | KI | 134000 nM |
| 4-aminophenol | KI | 159000 nM |
| benzene-1,3-diol | KI | 795000 nM |
| 1,2-Dihydroxybenzene, XI | KI | 4e+06 nM |
ChEMBL bioactivities
915 potent at pChembl≥5 of 988 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
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.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 2-chloro-5-[2-(5,6-dimethylbenzimidazol-1-yl)acetyl]benzenesulfonamide | 1373180: 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 assay | kd | <0.0001 | uM |
| N-(benzimidazol-1-yl)-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide | 1373180: 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 assay | kd | <0.0001 | uM |
| sulfane | 238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coli | ki | <0.0001 | uM |
| 5-[2-(benzimidazol-1-yl)acetyl]-2-chlorobenzenesulfonamide | 1373180: 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 assay | kd | <0.0001 | uM |
| Hydrogen Cyanide | 238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coli | ki | <0.0001 | uM |
| 5-[2-(benzimidazol-1-yl)acetyl]-2,4-dichlorobenzenesulfonamide | 1373180: 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 assay | kd | 0.0001 | uM |
| 5-[2-(benzimidazol-1-yl)acetyl]-2-chloro-4-(2-phenylethylsulfanyl)benzenesulfonamide | 1373180: 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 assay | kd | 0.0001 | uM |
| 2-chloro-5-(2-imidazol-1-ylacetyl)benzenesulfonamide | 1373180: 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 assay | kd | 0.0001 | uM |
| 2,4-dichloro-5-[2-(5,6-dimethylbenzimidazol-1-yl)acetyl]benzenesulfonamide | 1373180: 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 assay | kd | 0.0001 | uM |
| N-[(E)-benzylideneamino]-1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxamide | 1515318: 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 assay | kd | 0.0001 | uM |
| sulfamic acid | 238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coli | ki | 0.0001 | uM |
| 4-[1-[(2R)-1-(3-azabicyclo[3.2.2]nonan-3-yl)-3-methyl-1-oxobutan-2-yl]triazol-4-yl]benzenesulfonamide | 1557414: Inhibition of carbonic anhydrase (unknown origin) | ki | 0.0002 | uM |
| (2R)-3-phenyl-2-[4-(4-sulfamoylphenyl)triazol-1-yl]-N-(2-thiophen-3-ylethyl)propanamide | 1557414: Inhibition of carbonic anhydrase (unknown origin) | ki | 0.0002 | uM |
| 4-nitrobenzenesulfonamide | 50173: Compound was evaluated for the inhibition of Carbonic anhydrase | ki | 0.0002 | uM |
| (2R)-N-benzyl-3-methyl-2-[4-(4-sulfamoylphenyl)triazol-1-yl]butanamide | 1557414: Inhibition of carbonic anhydrase (unknown origin) | ki | 0.0002 | uM |
| N-[(E)-benzylideneamino]-5-oxo-1-(4-sulfamoylphenyl)pyrrolidine-3-carboxamide | 1515318: 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 assay | kd | 0.0003 | uM |
| 24530 | 238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coli | ki | 0.0003 | uM |
| 4-chlorobenzenesulfonamide | 50173: Compound was evaluated for the inhibition of Carbonic anhydrase | ki | 0.0003 | uM |
| 2-chloro-5-[2-(5,6-dimethylbenzimidazol-1-yl)acetyl]-4-phenylsulfanylbenzenesulfonamide | 1373180: 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 assay | kd | 0.0005 | uM |
| 1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxylic acid | 1515318: 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 assay | kd | 0.0005 | uM |
| N-(benzimidazol-1-yl)-2,4-dichloro-5-sulfamoylbenzamide | 1373180: 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 assay | kd | 0.0007 | uM |
| 2-benzylsulfanyl-4-chloro-N-cyclohexyl-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0008 | uM |
| N-(benzimidazol-1-yl)-4-chloro-2-phenylsulfanyl-5-sulfamoylbenzamide | 1373180: 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 assay | kd | 0.0008 | uM |
| Acetazolamide | 50175: Compound was evaluated for the inhibition of Carbonic anhydrase (Non competitive) | ki | 0.0008 | uM |
| sulfamide | 238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coli | ki | 0.0008 | uM |
| 4-chloro-2-cyclohexylsulfanyl-N-(2-methoxyethyl)-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0009 | uM |
| 2,4-dichloro-5-(2-imidazol-1-ylacetyl)benzenesulfonamide | 1373180: 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 assay | kd | 0.0009 | uM |
| N-butyl-4-chloro-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0011 | uM |
| N-benzyl-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0011 | uM |
| 4-[4-(hydrazinecarbonyl)-2-oxopyrrolidin-1-yl]-2,6-dimethylbenzenesulfonamide | 1515318: 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 assay | kd | 0.0011 | uM |
| methyl 4-[(4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzoyl)amino]butanoate | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0016 | uM |
| 4-[(4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzoyl)amino]butanoic acid | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0016 | uM |
| 2-benzylsulfanyl-N-butyl-4-chloro-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0017 | uM |
| 4-bromo-N-(2-hydroxyethyl)-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0020 | uM |
| 6-ethoxy-1,3-benzothiazole-2-sulfonamide | 239287: Mean inhibitory constant towards human carbonic anhydrase V determined by spectrophotometric dansylamide binding assay | ki | 0.0020 | uM |
| 2-benzylsulfanyl-4-chloro-N-(2-hydroxyethyl)-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0021 | uM |
| 4-chloro-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0022 | uM |
| N-(3-methyl-5-sulfamoyl-1,3,4-thiadiazol-2-ylidene)acetamide | 239287: Mean inhibitory constant towards human carbonic anhydrase V determined by spectrophotometric dansylamide binding assay | ki | 0.0025 | uM |
| N-butyl-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0026 | uM |
| methyl 4-[(2-benzylsulfanyl-4-chloro-5-sulfamoylbenzoyl)amino]butanoate | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0028 | uM |
| 4-pentylselanylbenzenesulfonamide | 1354956: Inhibition of human carbonic anhydrase 5A after 15 mins by stopped flow carbon dioxide hydration assay | ki | 0.0029 | uM |
| 2-benzylsulfanyl-4-bromo-N-(2-hydroxyethyl)-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0030 | uM |
| 4-bromo-N-butyl-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0035 | uM |
| 2-chloro-5-[2-(2-methylbenzimidazol-1-yl)acetyl]benzenesulfonamide | 1373180: 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 assay | kd | 0.0035 | uM |
| 4-chloro-2-cyclohexylsulfanyl-N-(3-hydroxypropyl)-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0036 | uM |
| 4-chloro-2-cyclohexylsulfanyl-N-(2-hydroxyethyl)-5-sulfamoylbenzamide | 1520083: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay | kd | 0.0039 | uM |
| 4-(2-methoxyethylselanyl)benzenesulfonamide | 1354956: Inhibition of human carbonic anhydrase 5A after 15 mins by stopped flow carbon dioxide hydration assay | ki | 0.0040 | uM |
| 2-chloro-5-[2-(3,4-dihydro-2H-quinolin-1-yl)acetyl]benzenesulfonamide | 1373180: 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 assay | kd | 0.0042 | uM |
| phenylboronic acid | 238688: Inhibitory activity against human carbonic anhydrase V expressed in Escherichia coli | ki | 0.0045 | uM |
| 2-chloro-5-[2-(2-ethylimidazol-1-yl)acetyl]benzenesulfonamide | 1373180: 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 assay | kd | 0.0047 | uM |
CTD chemical–gene interactions
34 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Aflatoxin B1 | increases methylation, affects expression, decreases expression | 4 |
| Acetaminophen | decreases expression | 2 |
| Benzo(a)pyrene | affects methylation, decreases expression | 2 |
| sulfamic acid | decreases activity | 1 |
| oryzalin | affects binding, decreases activity | 1 |
| sodium arsenite | decreases expression | 1 |
| butyraldehyde | decreases expression | 1 |
| chloric acid | decreases activity | 1 |
| sodium metasilicate | decreases activity | 1 |
| benzo(e)pyrene | decreases methylation | 1 |
| potassium periodate | decreases activity | 1 |
| molybdate | decreases activity | 1 |
| tungstate | decreases activity | 1 |
| K 7174 | decreases expression | 1 |
| perchlorate | decreases activity | 1 |
| Rosiglitazone | decreases expression | 1 |
| Acetazolamide | affects binding, decreases activity | 1 |
| Bromates | decreases activity | 1 |
| Carbonates | decreases activity | 1 |
| Diethylnitrosamine | decreases expression | 1 |
| Dimethyl Sulfoxide | increases expression | 1 |
| Iodates | decreases activity | 1 |
| Methapyrilene | decreases methylation | 1 |
| Pesticides | affects methylation | 1 |
| Thiram | increases expression | 1 |
| Tretinoin | decreases expression | 1 |
| Valproic Acid | decreases expression | 1 |
| Vanadates | decreases activity | 1 |
| Zinc | decreases expression | 1 |
| Propofol | decreases expression | 1 |
ChEMBL screening assays
144 unique, capped per target: 143 binding, 1 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL3386760 | Binding | Inhibition 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 |
| CHEMBL4406726 | ADMET | Inhibition of human recombinant carbonic anhydrase 5A preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assay | Phenyl(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.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT03655223 | Not specified | ENROLLING_BY_INVITATION | Early Check: Expanded Screening in Newborns |
Related Atlas pages
- Associated diseases: hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency
- Targeted by drugs: Amphetamine, Histamine
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency