CA1

Summary

CA1 (carbonic anhydrase 1, HGNC:1368) is a protein-coding gene on chromosome 8q21.2, encoding Carbonic anhydrase 1 (P00915). Catalyzes the reversible hydration of carbon dioxide.

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. This CA1 gene is closely linked to the CA2 and CA3 genes on chromosome 8. It encodes a cytosolic protein that is found at the highest level in erythrocytes. Allelic variants of this gene have been described in some populations. Alternative splicing and the use of alternative promoters results in multiple transcript variants.

Source: NCBI Gene 759 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 47 total — 4 pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 70 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001128831

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1368
Approved symbol	CA1
Name	carbonic anhydrase 1
Location	8q21.2
Locus type	gene with protein product
Status	Approved
Aliases	Car1
Ensembl gene	ENSG00000133742
Ensembl biotype	protein_coding
OMIM	114800
Entrez	759

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 21 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000431316, ENST00000517429, ENST00000517590, ENST00000517618, ENST00000518233, ENST00000518341, ENST00000519129, ENST00000519991, ENST00000520093, ENST00000520663, ENST00000520692, ENST00000520990, ENST00000521679, ENST00000521846, ENST00000522389, ENST00000522579, ENST00000522662, ENST00000522814, ENST00000523022, ENST00000523712, ENST00000523858, ENST00000523953, ENST00000524324, ENST00000542576, ENST00000626824, ENST00000875459, ENST00000875460, ENST00000875461

RefSeq mRNA: 7 — MANE Select: NM_001128831 NM_001128829, NM_001128830, NM_001128831, NM_001164830, NM_001291967, NM_001291968, NM_001738

CCDS: CCDS6237

Canonical transcript exons

ENST00000523022 — 8 exons

Exon	Start	End
ENSE00000795067	85329689	85329844
ENSE00002104230	85327608	85328676
ENSE00002123397	85378046	85378113
ENSE00003480271	85341599	85341659
ENSE00003506637	85338252	85338449
ENSE00003588058	85332490	85332552
ENSE00003668620	85333525	85333620
ENSE00003789786	85336945	85337063

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 99.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 15.8830 / max 7625.9018, expressed in 149 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93803	15.2752	145
93802	0.6078	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.96	gold quality
trabecular bone tissue	UBERON:0002483	99.90	gold quality
colonic mucosa	UBERON:0000317	99.85	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.83	gold quality
rectum	UBERON:0001052	99.82	gold quality
bone marrow cell	CL:0002092	99.59	gold quality
bone marrow	UBERON:0002371	98.89	gold quality
monocyte	CL:0000576	95.03	gold quality
colonic epithelium	UBERON:0000397	94.87	gold quality
ileal mucosa	UBERON:0000331	94.70	gold quality
mononuclear cell	CL:0000842	94.45	gold quality
transverse colon	UBERON:0001157	93.08	gold quality
blood	UBERON:0000178	92.28	gold quality
leukocyte	CL:0000738	89.52	gold quality
large intestine	UBERON:0000059	84.66	gold quality
colon	UBERON:0001155	84.08	gold quality
diaphragm	UBERON:0001103	83.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.08	gold quality
mucosa of paranasal sinus	UBERON:0005030	79.31	gold quality
superficial temporal artery	UBERON:0001614	78.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.86	silver quality
intestine	UBERON:0000160	77.73	gold quality
spleen	UBERON:0002106	75.81	gold quality
right lung	UBERON:0002167	73.42	gold quality
gingival epithelium	UBERON:0001949	72.14	gold quality
mucosa of urinary bladder	UBERON:0001259	72.06	gold quality
hair follicle	UBERON:0002073	72.01	gold quality
amniotic fluid	UBERON:0000173	71.60	gold quality
epithelial cell of pancreas	CL:0000083	71.16	gold quality
germinal epithelium of ovary	UBERON:0001304	70.16	silver quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	10920.16
E-CURD-6	yes	4463.17
E-HCAD-9	yes	4244.98
E-MTAB-9221	yes	3055.92
E-CURD-46	yes	1945.25
E-HCAD-15	yes	1019.06
E-GEOD-76312	yes	797.09
E-HCAD-6	yes	536.07
E-HCAD-4	yes	160.88
E-GEOD-125970	yes	30.86
E-MTAB-8410	yes	16.10
E-MTAB-9467	yes	4.31
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX2, GATA1, HOXB7, LMO2, MYB, NR1I3, TAL1

miRNA regulators (miRDB)

26 targeting CA1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-626	98.89	66.21	762
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-6839-5P	96.74	68.29	1088
HSA-MIR-378J	96.44	66.20	1020
HSA-MIR-431-5P	96.16	66.50	652

Literature-anchored findings (GeneRIF, showing 33)

• The X-ray crystallographic structure of the CA I Michigan 1 variant isozyme is reported, both in the presence and absence of a second bound zinc ion coordinated to His 64, His 200, and Arg 67. (PMID:12009884)
• concentrations in nondialyzed chronic kidney disease patients, and the relationship with acidosis, zinc, anemia, and iron supplementation (PMID:14675565)
• cytosolic CA I, II, and XIII are downregulated in neoplastic colorectal mucosa compared to normal colorectal mucosa (PMID:15836783)
• Isothiocyanato sulfonamide thioureas inhibit this enzyme. (PMID:15837325)
• X-ray crystallographic structure for the adduct of an activator with hCA I. Binding site interactions of activator L-Histidine with active site amino acids (PMID:16870440)
• study presents the X-ray structure of the foscarnet adduct with CA1 together with the factors governing recognition of such small molecules by a metalloenzyme active site (PMID:17314045)
• Decreased levels of carbonic anhydrase 1 isozyme is associated with type II diabetes. (PMID:17464559)
• single mutation of an amino acid not considered essential to catalysis (Phe91Asn) in carbonic anhydrase I, but is near substrate binding pocket, led to increase of catalytic activity; mutant CA I also showed higher affinity for sulfonamide inhibitors (PMID:20624682)
• Overexpression of CA1 in the synovial tissues of ankylosing spondylitis (AS) patients may promote improper calcification and bone resorption in AS. (PMID:21143847)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• A significant correlation was found between positive carbonic anhydrase I staining and oral squamous cell carcinoma for more advanced clinical stage and larger tumor size, but not for positive lymph node metastasis, distal metastasis, and recurrence. (PMID:22416960)
• carbonic anhydrase I, phosphoglycerate kinase 1 and apolipoprotein A-I appeared to be the most significant variations of proteins in patients with osteopenia and osteoarthritis (PMID:22619369)
• The gene encoding CA1 is susceptible to ankylosing spondylitis and plays a role in the process of bone formation. (PMID:22838845)
• The new prognostic biomarkers GRP78, Fructose-bisphosphate Aldolase A (ALDOA), Carbonic Anhydrase I (CA1) and Peptidyl-prolyl cis-trans isomerase A or Cyclophilin A (PPIA)) provided good survival prediction for TNM stage I-IV patients. (PMID:22996014)
• may be involved in the pathogenesis of Abdominal aortic aneurysm (PMID:23557951)
• Myocardial carbonic anhydrase 1/2 activation is significantly elevated in diabetic ischemic cardiomyopathy. (PMID:24670789)
• Structure-activity relationships study showed that indolylchalcone derivatives have higher inhibitory activities than pyrido[2,3-d]pyrimidine derivatives on hCA I and hCA II. (PMID:25165709)
• CA1 is highly expressed in the sera of stage I non-small cell lung cancer patients (PMID:26232327)
• CA1 is a potential oncogene and that it contributes to abnormal cell calcification, apoptosis and migration in breast cancer. (PMID:26459317)
• We report on the competitive zinc metalation of apo-carbonic anhydrase [CA; metal-free CA (apo-CA)] in the presence of apo-metallothionein 1A domain fragments to identify domain specific determinants of zinc binding and zinc donation (PMID:26475450)
• We demonstrated that resveratrol, caffeic acid, and tannic acid in stored blood could decrease the sensitivity to oxidation of erythrocytes in vitro but did not exhibit such effects on Carbonic Anhydrase activity. (PMID:27413740)
• Here are presented solved the first crystal structures of carbonic anhydrase 1and carbonic anhydrase 2 in complex with polmacoxib, at 2.0 A and 1.8 A, respectively. (PMID:27475498)
• Neuronal carbonic anhydrase I (CA1) appears to be associated with the endoplasmic reticulum subcellular structure. (PMID:27809276)
• Anti-CA I and II antibody levels were investigated using ELISA in serum samples from 30 patients with Acute Myeloid Leukemia (AML) and 30 healthy peers. Anti-CA I and II antibody titers in the AML group were significantly higher compared with the control group (p=0.0001 and 0.018, respectively). (PMID:28270370)
• These results showed that flavonoids especially malvin and oenin effectively inhibited hCA I and II isoenzymes. (PMID:28445001)
• Discovery of potent carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase enzymes inhibitors: The new amides and thiazolidine-4-ones synthesized on an acetophenone base. (PMID:28544359)
• These six-membered carbocycles showed nice inhibitory action against AChE and human carbonic anhydrase (hCA) II and I isoforms. The hCA I, II, and AChE were efficiently inhibited by these molecules, with Ki values in the range of 6.70-35.85 nM for hCA I, 18.77-60.84 nM for hCA II, and 0.74-4.60 for AChE, respectively (PMID:28613396)
• knock-down of the CA1 mRNA in tumour cells enhances/does not change the gene expression of the extracellular matrix (ECM) proteins. (PMID:28782909)
• Results indicate that the reduced expression of the carbonic anhydrase I (CA1) protein enhances the malignant potential of prostatic (PC3) tumour cells. (PMID:30916466)
• Overexpression of CA1 mRNA and the CA I Protein in Tumor Cells Does Not Change the Gene Expression of the ECM Proteins. (PMID:31963697)
• carbonic anhydrase 1 (CA1) and CA4 were identified as potential biomarkers of Colon adenocarcinoma due to their predictive roles in diagnosis and prognosis, and the results were further confirmed by a series of analyses. (PMID:32031891)
• The Effect of Nanoparticles on the Structure and Enzymatic Activity of Human Carbonic Anhydrase I and II. (PMID:32992797)
• Carbonic anhydrase activity in the frontal lobe of human brain. (PMID:33682938)

Cross-species orthologs

18 orthologs

Organism	Symbol	Gene ID
danio_rerio	cahz	ENSDARG00000011166
danio_rerio	ca2	ENSDARG00000014488
mus_musculus	Car1	ENSMUSG00000027556
rattus_norvegicus	Car1	ENSRNOG00000010698
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), CA10 (ENSG00000154975), CA3 (ENSG00000164879), CA4 (ENSG00000167434), CA7 (ENSG00000168748), CA5B (ENSG00000169239), CA5A (ENSG00000174990), CA8 (ENSG00000178538), CA13 (ENSG00000185015)

Protein

Protein identifiers

Carbonic anhydrase 1 — P00915 (reviewed: P00915)

Alternative names: Carbonate dehydratase I, Carbonic anhydrase B, Carbonic anhydrase I, Cyanamide hydratase CA1

All UniProt accessions (15): E5RFE7, E5RFL2, E5RG43, E5RG81, E5RGU8, E5RH81, P00915, E5RHP7, E5RHS7, E5RIF9, E5RII2, E5RJF6, E5RJI8, H0YBE2, V9HWE3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible hydration of carbon dioxide. Can hydrate cyanamide to urea.

Subcellular location. Cytoplasm.

Activity regulation. Activated by histamine, imidazole, L-adrenaline, L- and D-histidine, and L- and D-phenylalanine. Inhibited by coumarins, sulfonamide derivatives such as acetazolamide, benzenesulfonamide and derivatives (4-carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene-sulfonamide ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4-aminoethylbenzene-sulfonamide), and ‘prong inhibitors’ BR15, BR17, BR22 and BR30. Activated by a short exposition to Foscarnet (phosphonoformate trisodium salt), but inhibited by a long one. Esterase activity weakly reduced by cyanamide.

Similarity. Belongs to the alpha-carbonic anhydrase family.

RefSeq proteins (7): NP_001122301, NP_001122302, NP_001122303, NP_001158302, NP_001278896, NP_001278897, NP_001729 (=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), 2 shown:

• hydrogencarbonate + H(+) = CO2 + H2O (RHEA:10748)
• urea = cyanamide + H2O (RHEA:23056)

UniProt features (48 total): strand 16, helix 10, binding site 8, sequence variant 3, turn 3, region of interest 2, initiator methionine 1, chain 1, modified residue 1, sequence conflict 1, domain 1, active site 1

Structure

Experimental structures (PDB)

56 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7Q0D	X-RAY DIFFRACTION	1.24
8CDX	X-RAY DIFFRACTION	1.33
6I0J	X-RAY DIFFRACTION	1.35
6Y00	X-RAY DIFFRACTION	1.37
8S4F	X-RAY DIFFRACTION	1.39
6F3B	X-RAY DIFFRACTION	1.4
6I0L	X-RAY DIFFRACTION	1.4
5E2M	X-RAY DIFFRACTION	1.41
8Q7G	X-RAY DIFFRACTION	1.43
6XZO	X-RAY DIFFRACTION	1.44
8CDZ	X-RAY DIFFRACTION	1.44
7PLF	X-RAY DIFFRACTION	1.46
9EP2	X-RAY DIFFRACTION	1.47
7ZL5	X-RAY DIFFRACTION	1.48
4WR7	X-RAY DIFFRACTION	1.5
6EVR	X-RAY DIFFRACTION	1.5
6XZS	X-RAY DIFFRACTION	1.53
6XZE	X-RAY DIFFRACTION	1.54
2FOY	X-RAY DIFFRACTION	1.55
2NMX	X-RAY DIFFRACTION	1.55
6XZX	X-RAY DIFFRACTION	1.55
8RLO	X-RAY DIFFRACTION	1.55
1HCB	X-RAY DIFFRACTION	1.6
6EX1	X-RAY DIFFRACTION	1.6
9HWN	X-RAY DIFFRACTION	1.6
8QUN	X-RAY DIFFRACTION	1.61
6HWZ	X-RAY DIFFRACTION	1.64
2NN1	X-RAY DIFFRACTION	1.65
6XZY	X-RAY DIFFRACTION	1.66
6G3V	X-RAY DIFFRACTION	1.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00915-F1	96.97	0.98

Functional residue map

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

Catalytic / active sites (1): 65 (proton donor/acceptor)

Ligand- & substrate-binding residues (8): 120; 200–201; 200; 201 (in variant michigan-1); 65 (in variant michigan-1); 68 (in variant michigan-1); 95; 97

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1237044	Erythrocytes take up carbon dioxide and release oxygen
R-HSA-1247673	Erythrocytes take up oxygen and release carbon dioxide
R-HSA-1475029	Reversible hydration of carbon dioxide
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1430728	Metabolism
R-HSA-1480926	O2/CO2 exchange in erythrocytes
R-HSA-168256	Immune System
R-HSA-382551	Transport of small molecules
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-9020591	Interleukin-12 signaling

MSigDB gene sets: 132 (showing top): GNF2_PRDX2, GOMF_CARBONATE_DEHYDRATASE_ACTIVITY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, RIZKI_TUMOR_INVASIVENESS_3D_DN, SHEPARD_BMYB_MORPHOLINO_DN, GOLDRATH_ANTIGEN_RESPONSE, GNF2_ANK1, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, RHEIN_ALL_GLUCOCORTICOID_THERAPY_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GNF2_SPTA1, GATA1_03

GO Biological Process (1): response to fructose (GO:0009750)

GO Molecular Function (8): arylesterase activity (GO:0004064), carbonate dehydratase activity (GO:0004089), zinc ion binding (GO:0008270), hydro-lyase activity (GO:0016836), cyanamide hydratase activity (GO:0018820), protein binding (GO:0005515), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
O2/CO2 exchange in erythrocytes	2
Metabolism	1
Interleukin-12 signaling	1
Immune System	1
Transport of small molecules	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Interleukin-12 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hydro-lyase activity	2
cellular anatomical structure	2
response to hexose	1
carboxylic ester hydrolase activity	1
transition metal ion binding	1
carbon-oxygen lyase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

1770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CA1	CYP24A1	Q07973	879
CA1	ALB	P02768	657
CA1	ATP6V1B1	P15313	638
CA1	PRDX2	P31945	631
CA1	PADI2	Q9Y2J8	593
CA1	SLC2A5	P22732	588
CA1	KANSL3	Q9P2N6	557
CA1	SORD	Q00796	546
CA1	ACHE	P22303	546
CA1	SP6	Q3SY56	542
CA1	ENO1	P06733	534
CA1	MAFK	O60675	497
CA1	TG	P01266	492
CA1	BACH2	Q9BYV9	491
CA1	CA6	P23280	491

IntAct

15 interactions, top by confidence:

A	B	Type	Score
CA1	TFCP2	psi-mi:“MI:0915”(physical association)	0.720
CA1	E7	psi-mi:“MI:0915”(physical association)	0.370
CA1	HSD17B7	psi-mi:“MI:0915”(physical association)	0.370
MAPK6	CA1	psi-mi:“MI:0915”(physical association)	0.370
UPF3A	CASC3	psi-mi:“MI:0914”(association)	0.350
ARMH1	TUSC2	psi-mi:“MI:0914”(association)	0.350
KCNG4	CA1	psi-mi:“MI:0914”(association)	0.350
NTF3	CA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): TFCP2 (Two-hybrid), TFCP2 (Two-hybrid), CA1 (Affinity Capture-MS), CA1 (Affinity Capture-MS), CA1 (Affinity Capture-MS), CA1 (Affinity Capture-MS), CA1 (Affinity Capture-MS), CA1 (Affinity Capture-MS), CA1 (Affinity Capture-MS), CA1 (Affinity Capture-MS), CA1 (Two-hybrid), CA1 (Co-fractionation), CA1 (Co-fractionation), CA1 (Two-hybrid), HSD17B7 (Two-hybrid)

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

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	33
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1341980	GRCh37/hg19 8q21.11-21.3(chr8:75904944-87097083)x1	Pathogenic
17605	NM_001128831.4(CA1):c.760G>C (p.Gly254Arg)	Pathogenic
17606	NM_001128831.4(CA1):c.740G>A (p.Arg247His)	Pathogenic
60377	GRCh38/hg38 8q21.11-21.2(chr8:73879385-85611466)x1	Pathogenic

SpliceAI

1055 predictions. Top by Δscore:

Variant	Effect	Δscore
8:85328674:CAG:C	acceptor_gain	1.0000
8:85329714:T:A	donor_gain	1.0000
8:85329840:TTGCC:T	acceptor_gain	1.0000
8:85329841:TGCC:T	acceptor_gain	1.0000
8:85329843:CC:C	acceptor_gain	1.0000
8:85329843:CCCTG:C	acceptor_loss	1.0000
8:85329844:CC:C	acceptor_gain	1.0000
8:85329845:C:CC	acceptor_gain	1.0000
8:85329845:CT:C	acceptor_loss	1.0000
8:85329846:T:C	acceptor_loss	1.0000
8:85332553:C:CG	acceptor_loss	1.0000
8:85332554:T:A	acceptor_loss	1.0000
8:85333520:CTCA:C	donor_loss	1.0000
8:85333521:TCA:T	donor_loss	1.0000
8:85333522:CACC:C	donor_loss	1.0000
8:85333523:A:T	donor_loss	1.0000
8:85333524:C:CG	donor_loss	1.0000
8:85333621:C:CC	acceptor_gain	1.0000
8:85337064:C:CC	acceptor_gain	1.0000
8:85338246:GCTCA:G	donor_loss	1.0000
8:85338247:CTCA:C	donor_loss	1.0000
8:85338248:TCACC:T	donor_loss	1.0000
8:85338249:CAC:C	donor_loss	1.0000
8:85338250:A:C	donor_loss	1.0000
8:85328672:GCCAG:G	acceptor_gain	0.9900
8:85328673:CCAG:C	acceptor_gain	0.9900
8:85328673:CCAGC:C	acceptor_gain	0.9900
8:85328674:CAGC:C	acceptor_gain	0.9900
8:85328676:GC:G	acceptor_loss	0.9900
8:85328677:C:CA	acceptor_loss	0.9900

AlphaMissense

1724 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:85328607:G:T	R247S	0.996
8:85338438:A:G	W17R	0.995
8:85338438:A:T	W17R	0.995
8:85328581:T:A	R255S	0.994
8:85328581:T:G	R255S	0.994
8:85329730:A:G	W210R	0.994
8:85329730:A:T	W210R	0.994
8:85337007:A:G	W98R	0.994
8:85337007:A:T	W98R	0.994
8:85338436:C:A	W17C	0.994
8:85338436:C:G	W17C	0.994
8:85336979:T:A	E107V	0.993
8:85338395:G:T	P31H	0.993
8:85329768:C:T	G197D	0.992
8:85337005:C:A	W98C	0.992
8:85337005:C:G	W98C	0.992
8:85338392:A:T	V32D	0.992
8:85333619:A:G	L119P	0.991
8:85338301:A:C	N62K	0.991
8:85338301:A:T	N62K	0.991
8:85329766:A:G	S198P	0.990
8:85329782:G:C	F192L	0.990
8:85329782:G:T	F192L	0.990
8:85329784:A:G	F192L	0.990
8:85337010:G:C	H97D	0.990
8:85328582:C:G	R255T	0.989
8:85329781:A:G	W193R	0.989
8:85329781:A:T	W193R	0.989
8:85328606:C:G	R247P	0.988
8:85328663:C:G	R228P	0.988

dbSNP variants (sampled 300 via entrez): RS1000013899 (8:85344466 G>A,C), RS1000030142 (8:85337778 A>G,T), RS1000051385 (8:85372169 C>T), RS1000162645 (8:85351033 C>T), RS1000219995 (8:85351539 C>T), RS1000318601 (8:85376796 G>A), RS1000320060 (8:85344165 T>A), RS1000342921 (8:85358184 A>G), RS1000371204 (8:85378737 T>A), RS1000389408 (8:85358502 C>A,G), RS1000423140 (8:85351825 G>C), RS1000503079 (8:85349418 T>A,G), RS1000532977 (8:85327586 G>C), RS1000632456 (8:85356550 C>T), RS1000638020 (8:85367092 T>C)

Disease associations

OMIM: gene MIM:114800 | disease phenotypes: MIM:614230

GenCC curated gene-disease

Mondo (4): chromosome 8q21.11 deletion syndrome (MONDO:0013646), metabolic acidosis (MONDO:0000440), renal tubular acidosis (MONDO:0001909), rickets (MONDO:0005520)

Orphanet (1): 8q21.11 microdeletion syndrome (Orphanet:284160)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0002748	Rickets

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002040_1	Blood trace element (Zn levels)	6.000000e-12
GCST002934_16	Zinc levels	6.000000e-06
GCST004611_37	High light scatter reticulocyte count	5.000000e-11
GCST004612_44	High light scatter reticulocyte percentage of red cells	2.000000e-10
GCST004619_91	Reticulocyte fraction of red cells	1.000000e-09
GCST004622_17	Reticulocyte count	2.000000e-10
GCST006585_2230	Blood protein levels	2.000000e-09
GCST90002385_405	High light scatter reticulocyte count	4.000000e-37
GCST90002386_483	High light scatter reticulocyte percentage of red cells	3.000000e-35
GCST90002391_187	Mean corpuscular hemoglobin concentration	5.000000e-24
GCST90002392_586	Mean corpuscular volume	5.000000e-15
GCST90002396_430	Mean reticulocyte volume	1.000000e-30
GCST90002397_341	Mean spheric corpuscular volume	3.000000e-20
GCST90002405_514	Reticulocyte count	7.000000e-34
GCST90002406_304	Reticulocyte fraction of red cells	9.000000e-30

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D000141	Acidosis, Renal Tubular	C12.050.351.968.419.815.093; C12.200.777.419.815.093; C12.950.419.815.093; C16.320.831.093; C18.452.076.176.210
D012279	Rickets	C05.116.198.816; C18.452.104.816; C18.452.174.845; C18.654.521.500.133.770.734

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095180 (PROTEIN FAMILY), CHEMBL261 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

70 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 5,536,680 (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
CHEMBL1054	TRICHLORMETHIAZIDE	4	11,619
CHEMBL1055	CHLORTHALIDONE	4	20,442
CHEMBL112	ACETAMINOPHEN	4	157,242
CHEMBL1161681	NITROUS ACID	4	286,808
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1235452	SULFUR	4	2,163,993
CHEMBL1286	LEVETIRACETAM	4	13,997
CHEMBL1354	SODIUM ACETATE	4	594,259
CHEMBL14060	PHENOL	4	1,871,332
CHEMBL17	DICHLORPHENAMIDE	4	9,022
CHEMBL18	ETHOXZOLAMIDE	4	3,042
CHEMBL21	SULFANILAMIDE	4	153,075
CHEMBL2105581	VERALIPRIDE	4	1,165
CHEMBL218490	DORZOLAMIDE	4	10,216
CHEMBL220491	BRINZOLAMIDE	4	8,355
CHEMBL220492	TOPIRAMATE	4	35,160
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL26	SULPIRIDE	4
CHEMBL325041	BORTEZOMIB	4
CHEMBL328560	SULTHIAME	4
CHEMBL35	FUROSEMIDE	4
CHEMBL406	INDAPAMIDE	4
CHEMBL419	MAFENIDE	4
CHEMBL421	SULFASALAZINE	4
CHEMBL424	SALICYLIC ACID	4
CHEMBL435	HYDROCHLOROTHIAZIDE	4
CHEMBL443052	TAVABOROLE	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Carbonic anhydrases

Most potent curated ligand interactions (18 total), top 18:

Ligand	Action	Affinity	Parameter
benzolamide	Inhibition	7.82	pKi
ethoxzolamide	Inhibition	7.6	pKi
methocarbamol	Inhibition	7.6	pKi
indisulam	Inhibition	7.51	pKi
methazolamide	Inhibition	7.48	pKi
zonisamide	Inhibition	7.25	pKi
diclofenamide	Inhibition	7.13	pKi
compound 11 [PMID: 41150938]	Inhibition	6.84	pKi
acetazolamide	Inhibition	6.6	pKi
topiramate	Inhibition	6.6	pKi
chlorthalidone	Inhibition	6.46	pKi
compound 5a [PMID: 31287314]	Inhibition	6.07	pKi
compound 5b [PMID: 31287314]	Inhibition	6.05	pKi
sulpiride	Inhibition	5.92	pKi
gallic acid	Inhibition	5.5	pKi
SLC-0111	Inhibition	5.29	pKi
brinzolamide	Inhibition	4.35	pKi
dorzolamide	Inhibition	4.3	pKi

Binding affinities (BindingDB)

614 measured of 806 human assays (901 total across all organisms); most potent 50 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
(3aR,4S,7R,7aS)-2-(4-((E)-3-(2-bromophenyl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7k)	KI	0.405 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(4-bromophenyl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7i)	KI	0.442 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(3-methoxyphenyl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7b)	KI	0.469 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(4-chlorophenyl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7f)	KI	0.475 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(3-bromophenyl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7j)	KI	0.501 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(4-methoxyphenyl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7a)	KI	0.513 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(3-chlorophenyl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7g)	KI	0.518 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(m-tolyl)acryloyl)phenyl)-3a,4,7,7atetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7d)	KI	0.523 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(o-tolyl)acryloyl)phenyl)-3a,4,7,7atetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7e)	KI	0.529 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(pyridin-4-yl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7n)	KI	0.549 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(furan-2-yl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7l)	KI	0.595 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(p-tolyl)acryloyl)phenyl)-3a,4,7,7atetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7c)	IC50	0.597 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(2-chlorophenyl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7h)	KI	0.603 nM
(3aR,4S,7R,7aS)-2-(4-((E)-3-(thiophen-2-yl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (7m)	KI	0.636 nM
N-Pentafluorophenylsulfonyl-N-4-nitrobenzyl-glycine hydroxamate	KI	0.7 nM
N-hydroxy-2-{(4-nitrophenyl)methylsulfonamido}propanamide	KI	0.7 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxy-3-methylbutanamide	KI	0.8 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxy-4-methylpentanamide	KI	0.8 nM
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}propanamide	KI	0.8 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxypropanamide	KI	0.9 nM
2-N-(4-amino-3-bromo-5-fluorobenzene)-1,3,4-thiadiazole-2,5-disulfonamide	KI	1 nM
5-(4-Amino-3,5-dibromobenzenesulfonamido)-1,3,4-thiadiazole-2-sulfonamide	KI	1 nM
5-(4-Amino-3,5-dichlorobenzenesulfonamido)-1,3,4-thiadiazole-2-sulfonamide	KI	1.1 nM
5-{[(4-amino-3-bromo-5-chlorophenyl)sulfonyl]amino}-1,3,4-thiadiazole-2-sulfonamide	KI	1.3 nM
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}acetamide	KI	1.4 nM
N-hydroxy-2-{(4-nitrophenyl)methylsulfonamido}propanamide	KI	1.4 nM
2-N-(4-amino-3-chloro-5-fluorobenzene)-1,3,4-thiadiazole-2,5-disulfonamide	KI	1.4 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxyacetamide	KI	1.5 nM
N-hydroxy-2-{(4-nitrophenyl)methylsulfonamido}acetamide	KI	1.5 nM
2-{(2-chlorophenyl)methylsulfonamido}-N-hydroxypropanamide	KI	1.5 nM
2-N-(4-amino-3-chloro-5-iodobenzene)-1,3,4-thiadiazole-2,5-disulfonamide	KI	1.6 nM
2-Chloro-4-{[2-(methylthio)-1H-benzimidazol-1-yl]acetyl}-benzenesulfonamide (2j)	KD	1.67 nM
2-N-(4-amino-3-fluoro-5-iodobenzene)-1,3,4-thiadiazole-2,5-disulfonamide	KI	1.7 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxy-4-methylpentanamide	KI	1.9 nM
5-(4-Amino-3-bromobenzenesulfonamido)-1,3,4-thiadiazole-2-sulfonamide	KI	1.9 nM
5-{[(4-amino-3-bromo-5-iodophenyl)sulfonyl]amino}-1,3,4-thiadiazole-2-sulfonamide	KI	1.9 nM
2-N-(4-amino-3-iodobenzene)-1,3,4-thiadiazole-2,5-disulfonamide	KI	2.1 nM
5-(4-Amino-3,5-diiodobenzenesulfonamido)-1,3,4-thiadiazole-2-sulfonamide	KI	2.1 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxy-3-methylbutanamide	KI	2.4 nM
2-N-(4-amino-3-chlorobenzene)-1,3,4-thiadiazole-2,5-disulfonamide	KI	2.5 nM
2-Chloro-4-[(2-propyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (2f)	KD	2.86 nM
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}propanamide	KI	2.9 nM
Sulfonamide, 8	KI	3 nM
1-N-[5-Sulfamoyl-1,3,4-thiadiazol-2-yl-(aminosulfonyl-4-phenyl)]-2,3,4,6-tetramethylpyridinium perchlorate	KI	3 nM
2,3,6-trimethyl-4-phenyl-1-{4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}-1-pyridin-1-ylium perchlorate	KI	3 nM
2-N-(4-amino-3-fluorobenzene)-1,3,4-thiadiazole-2,5-disulfonamide	KI	3.1 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxypropanamide	KI	3.2 nM
4-[(2-Butyl-1H-benzimidazol-1-yl)acetyl]-2-chlorobenzenesulfonamide (2g)	KD	3.33 nM
4-{[2-(Methylsulfanyl)-1H-benzimidazol-1-yl]acetyl}benzenesulfonamide (1j)	KD	3.57 nM

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL3608873
11.00	Ki	0.01	nM	CHEMBL3608874
10.54	Kd	0.029	nM	CHEMBL3797893
10.48	Kd	0.033	nM	CHEMBL2333418
10.34	Ki	0.0459	nM	CHEMBL3585779
10.32	Ki	0.0483	nM	CHEMBL3585777
10.30	Kd	0.05	nM	CHEMBL2333397
10.30	Kd	0.05	nM	CHEMBL2333816
10.30	Ki	0.05	nM	CHEMBL3608890
10.17	Kd	0.067	nM	CHEMBL2333409
10.16	Ki	0.069	nM	CHEMBL6143639
10.05	Ki	0.09	nM	CHEMBL3608894
10.00	Kd	0.1	nM	CHEMBL2333402
10.00	Kd	0.1	nM	CHEMBL2333814
9.96	Kd	0.11	nM	CHEMBL2333416
9.92	Ki	0.12	nM	CHEMBL4100496
9.92	Ki	0.12	nM	CHEMBL4073678
9.90	Ki	0.1271	nM	CHEMBL3585776
9.90	Ki	0.127	nM	CHEMBL3585775
9.89	Kd	0.13	nM	CHEMBL2333408
9.89	Kd	0.13	nM	CHEMBL2333815
9.86	Ki	0.1397	nM	CHEMBL3585778
9.85	IC50	0.14	nM	CHEMBL4100496
9.85	Kd	0.14	nM	CHEMBL4577993
9.82	Kd	0.15	nM	CHEMBL4560953
9.82	Kd	0.15	nM	CHEMBL4553790
9.77	Kd	0.17	nM	CHEMBL2333405
9.72	Kd	0.19	nM	CHEMBL4516072
9.70	Kd	0.2	nM	CHEMBL2333406
9.70	Kd	0.2	nM	CHEMBL2333404
9.70	Kd	0.2	nM	CHEMBL2333419
9.70	Kd	0.2	nM	CHEMBL2333417
9.70	Ki	0.2	nM	CHEMBL4552380
9.70	Ki	0.2	nM	CHEMBL4460315
9.70	Ki	0.2	nM	CHEMBL4434661
9.70	Ki	0.2	nM	CHEMBL282157
9.68	IC50	0.21	nM	CHEMBL4073678
9.66	Kd	0.22	nM	CHEMBL4441652
9.64	Kd	0.23	nM	CHEMBL4567916
9.64	Kd	0.23	nM	CHEMBL4462447
9.62	Kd	0.24	nM	CHEMBL4448119
9.60	Kd	0.25	nM	CHEMBL2333407
9.60	Kd	0.25	nM	CHEMBL2333403
9.60	Kd	0.25	nM	CHEMBL4587295
9.56	Ki	0.2747	nM	CHEMBL3585780
9.55	IC50	0.28	nM	CHEMBL4098116
9.54	IC50	0.29	nM	CHEMBL4082551
9.54	IC50	0.29	nM	CHEMBL4097972
9.54	IC50	0.288	nM	CHEMBL4099344
9.54	Kd	0.29	nM	CHEMBL4516858

PubChem BioAssay actives

4400 with measured affinity, of 6100 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
benzyl N-[1-(3,4-dimethoxyphenyl)ethylsulfamoyl]carbamate	1231566: Inhibition of esterase activity of carbonic anhydrase 1 in human erythrocytes using PNF as substrate by spectrophotometer analysis	ki	<0.0001	uM
benzyl N-[1-(2,6-dimethoxyphenyl)ethylsulfamoyl]carbamate	1231566: Inhibition of esterase activity of carbonic anhydrase 1 in human erythrocytes using PNF as substrate by spectrophotometer analysis	ki	<0.0001	uM
4-[2-(pyrrolidine-1-carbonyl)-1,3-oxazol-5-yl]benzenesulfonamide	1242115: Inhibition of human recombinant carbonic anhydrase 1 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
4-[2-(morpholine-4-carbonyl)-1,3-oxazol-5-yl]benzenesulfonamide	1242115: Inhibition of human recombinant carbonic anhydrase 1 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
benzyl N-[1-(2-methoxyphenyl)ethylsulfamoyl]carbamate	1231566: Inhibition of esterase activity of carbonic anhydrase 1 in human erythrocytes using PNF as substrate by spectrophotometer analysis	ki	0.0001	uM
benzyl N-[1-(4-methoxyphenyl)ethylsulfamoyl]carbamate	1231566: Inhibition of esterase activity of carbonic anhydrase 1 in human erythrocytes using PNF as substrate by spectrophotometer analysis	ki	0.0001	uM
benzyl N-[1-(2,5-dimethoxyphenyl)ethylsulfamoyl]carbamate	1231566: Inhibition of esterase activity of carbonic anhydrase 1 in human erythrocytes using PNF as substrate by spectrophotometer analysis	ki	0.0001	uM
4-(2-methyl-1,3-oxazol-5-yl)thiophene-2-sulfonamide	1242115: Inhibition of human recombinant carbonic anhydrase 1 preincubated for 15 mins by stopped flow CO2 hydration method	ki	0.0001	uM
4-[2-(morpholine-4-carbonyl)-1,3-oxazol-5-yl]thiophene-2-sulfonamide	1242115: Inhibition of human recombinant carbonic anhydrase 1 preincubated for 15 mins by stopped flow CO2 hydration method	ki	0.0001	uM
2-[(5-anilino-1,3,4-thiadiazol-2-yl)sulfanyl]-N-[(E)-[5-(2-nitrophenyl)furan-2-yl]methylideneamino]acetamide	1453371: Non-competitive inhibition of carbonic anhydrase-1 in human erythrocyte membranes assessed as reduction in H+ release using CO2 as substrate by Lineweaver-Burk plot analysis	ki	0.0001	uM
2-[(5-anilino-1,3,4-thiadiazol-2-yl)sulfanyl]-N-[(E)-[5-(4-chlorophenyl)furan-2-yl]methylideneamino]acetamide	1453368: Inhibition of carbonic anhydrase-1 in human erythrocyte membranes assessed as reduction in H+ release using CO2 as substrate by bromine thymol blue indicator based assay	ic50	0.0001	uM
1-(2-bromophenyl)-5-oxo-N-(4-sulfamoylphenyl)pyrrolidine-3-carboxamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0001	uM
1-(3,5-dimethyl-4-sulfamoylphenyl)-N-[(E)-(4-nitrophenyl)methylideneamino]-5-oxopyrrolidine-3-carboxamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0001	uM
1-[[1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carbonyl]amino]-3-phenylthiourea	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	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
methyl 1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxylate	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0002	uM
N-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxo-1-phenylpyrrolidine-3-carboxamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0002	uM
1-(3-bromophenyl)-5-oxo-N-(4-sulfamoylphenyl)pyrrolidine-3-carboxamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	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-[4-(3,5-dimethylpyrazole-1-carbonyl)-2-oxopyrrolidin-1-yl]-2,6-dimethylbenzenesulfonamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0002	uM
1-methoxy-2-[1-(sulfamoylamino)ethyl]benzene	1231566: Inhibition of esterase activity of carbonic anhydrase 1 in human erythrocytes using PNF as substrate by spectrophotometer analysis	ki	0.0003	uM
2-[(5-anilino-1,3,4-thiadiazol-2-yl)sulfanyl]-N-[(E)-[5-(4-nitrophenyl)furan-2-yl]methylideneamino]acetamide	1453368: Inhibition of carbonic anhydrase-1 in human erythrocyte membranes assessed as reduction in H+ release using CO2 as substrate by bromine thymol blue indicator based assay	ic50	0.0003	uM
[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl] N-morpholin-4-ylcarbamodithioate	1459104: Inhibition of human erythrocyte carbonic anhydrase-1	ic50	0.0003	uM
2-[(5-anilino-1,3,4-thiadiazol-2-yl)sulfanyl]-N-[(E)-[5-(2,4-dichlorophenyl)furan-2-yl]methylideneamino]acetamide	1453368: Inhibition of carbonic anhydrase-1 in human erythrocyte membranes assessed as reduction in H+ release using CO2 as substrate by bromine thymol blue indicator based assay	ic50	0.0003	uM
2-[(5-anilino-1,3,4-thiadiazol-2-yl)sulfanyl]-N-[(E)-[5-(4-chloro-2-nitrophenyl)furan-2-yl]methylideneamino]acetamide	1453368: Inhibition of carbonic anhydrase-1 in human erythrocyte membranes assessed as reduction in H+ release using CO2 as substrate by bromine thymol blue indicator based assay	ic50	0.0003	uM
[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl] N-thiomorpholin-4-ylcarbamodithioate	1459104: Inhibition of human erythrocyte carbonic anhydrase-1	ic50	0.0003	uM
N-[(E)-benzylideneamino]-1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0003	uM
3-chloro-4-[4-(3,5-dimethylpyrazole-1-carbonyl)-2-oxopyrrolidin-1-yl]-2,6-dimethylbenzenesulfonamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0003	uM
1-(3,5-dimethyl-4-sulfamoylphenyl)-N-[(E)-(4-methoxyphenyl)methylideneamino]-5-oxopyrrolidine-3-carboxamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0003	uM
N-[(E)-(4-chlorophenyl)methylideneamino]-1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0003	uM
(1R,2S,6R,7S)-4-[4-[(E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
(1R,2S,6R,7S)-4-[4-[(E)-3-(3-methoxyphenyl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
(1R,2S,6R,7S)-4-[4-[(E)-3-(4-methylphenyl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
(1R,2S,6R,7S)-4-[4-[(E)-3-(3-methylphenyl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
(1R,2S,6R,7S)-4-[4-[(E)-3-(2-methylphenyl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
(1R,2S,6R,7S)-4-[4-[(E)-3-(4-chlorophenyl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
(1R,2S,6R,7S)-4-[4-[(E)-3-(3-chlorophenyl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
(1S,2R,6S,7R)-4-[4-[(E)-3-(2-chlorophenyl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
(1R,2S,6R,7S)-4-[4-[(E)-3-(4-bromophenyl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1802576: Esterase Activity Assay from Article 10.1016/j.bioorg.2016.12.001: “Synthesis, characterization, anticancer, antimicrobial and carbonic anhydrase inhibition profiles of novel (3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl) phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives.”	ki	0.0004	uM
(1S,2R,6S,7R)-4-[4-[(E)-3-(3-bromophenyl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
(1R,2S,6R,7S)-4-[4-[(E)-3-(2-bromophenyl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1802576: Esterase Activity Assay from Article 10.1016/j.bioorg.2016.12.001: “Synthesis, characterization, anticancer, antimicrobial and carbonic anhydrase inhibition profiles of novel (3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl) phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives.”	ki	0.0004	uM
(1S,2R,6S,7R)-4-[4-[(E)-3-(furan-2-yl)prop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
(1S,2R,6S,7R)-4-[4-[(E)-3-thiophen-2-ylprop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
(1S,2R,6S,7R)-4-[4-[(E)-3-pyridin-4-ylprop-2-enoyl]phenyl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione	1849566: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis	ki	0.0004	uM
2-[(5-anilino-1,3,4-thiadiazol-2-yl)sulfanyl]-N-[(E)-[5-(3,4-dichlorophenyl)furan-2-yl]methylideneamino]acetamide	1453368: Inhibition of carbonic anhydrase-1 in human erythrocyte membranes assessed as reduction in H+ release using CO2 as substrate by bromine thymol blue indicator based assay	ic50	0.0004	uM
4-chloro-2-(cyclooctylamino)-5-sulfamoylbenzoic acid	1361381: Binding affinity to recombinant human carbonic anhydrase 1 expressed in Escherichia coli assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	0.0004	uM
N-[(E)-(4-bromophenyl)methylideneamino]-1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0004	uM
N-(3,5-dimethylpyrazol-1-yl)-1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0004	uM
1-[[1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carbonyl]amino]-3-phenylthiourea	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0004	uM
N-[(E)-benzylideneamino]-5-oxo-1-(4-sulfamoylphenyl)pyrrolidine-3-carboxamide	1515314: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0004	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetazolamide	affects binding, decreases activity, decreases reaction	15
sodium arsenite	decreases expression, increases expression	2
Pyrimidines	decreases activity	2
Tobacco Smoke Pollution	decreases expression	2
3-methylpentyl(4-sulphamoylphenyl)carbamate	decreases activity	1
thiosemicarbazide	decreases activity	1
sulfamic acid	decreases activity	1
oryzalin	affects binding, decreases activity	1
silychristin	decreases activity	1
cobaltous chloride	decreases expression	1
chloric acid	decreases activity	1
sodium metasilicate	decreases activity	1
chalcone epoxide	affects binding, decreases activity	1
coumarin	decreases activity	1
2,6-di-tert-butylphenol	decreases activity	1
2,6-xylenol	decreases activity	1
potassium periodate	decreases activity	1
1,2,4-triazole	decreases activity	1
tungstate	decreases activity	1
pelargonidin-3-glucoside	decreases activity	1
candesartan	decreases activity	1
CGP 52608	affects binding, increases reaction	1
vanillin	decreases activity	1
N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide	affects binding, decreases activity	1
malvidin-3-glucoside	decreases activity	1
perchlorate	decreases activity	1
malvin	decreases activity	1
Sulfanilamide	decreases activity	1
Rosiglitazone	affects expression	1
Topiramate	affects binding, decreases activity	1

ChEMBL screening assays

886 unique, capped per target: 852 binding, 32 admet, 2 functional

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
CHEMBL4013794	ADMET	Inhibition of recombinant human carbonic anhydrase 1 preincubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay	3-Hydroxy-1H-quinazoline-2,4-dione as a New Scaffold To Develop Potent and Selective Inhibitors of the Tumor-Associated Carbonic Anhydrases IX and XII. — J Med Chem
CHEMBL834886	Functional	Inhibition constant against human recombinant carbonic anhydrase I	Carbonic anhydrase inhibitors. Synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with boron-containing sulfonamides, sulfamides, and sulfamates: toward agents for boron neutron capture therapy of hypoxic tumors. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 4 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_IX35	GM02744	Transformed cell line	Female
CVCL_IX36	GM02745	Transformed cell line	Male
CVCL_N002	GM02742	Transformed cell line	Male
CVCL_N003	GM02743	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03035812	PHASE4	COMPLETED	Alkalinization by Urologists & Nephrologists
NCT03846258	PHASE4	WITHDRAWN	High Versus Low Bicarbonate Bath in Critically-ill Patients Receiving Continuous Renal Replacement Therapy
NCT05005793	PHASE4	RECRUITING	Effect of Alkali Therapy on Vascular and Graft Function in Kidney Transplant Recipients
NCT07424625	PHASE4	NOT_YET_RECRUITING	A Study of Tris-Hydroxymethyl Aminomethane (THAM) Versus Sodium Bicarbonate in Cardiac Surgical Patients
NCT07464431	PHASE4	NOT_YET_RECRUITING	Sodium Bicarbonate for Critically Ill Patients With Metabolic Acidosis and Acute Kidney Injury
NCT00949832	PHASE4	COMPLETED	Vitamin D and Genetics in Nutritional Rickets
NCT01067898	PHASE4	COMPLETED	A Study on Oral Vitamin D Megadoses
NCT01578434	PHASE4	COMPLETED	Role of Calcium And Vitamin D In Nutritional Rickets And It’s Management
NCT03403933	PHASE4	COMPLETED	Vitamin D Supplementation on in Major Orthopedic Surgery
NCT01640119	PHASE3	UNKNOWN	Correction of Metabolic Acidosis in End Stage Renal Disease (ESRD)
NCT02476253	PHASE3	COMPLETED	Sodium Bicarbonate to Treat Severe Acidosis in the Critically Ill
NCT03317444	PHASE3	COMPLETED	Evaluation of TRC101 in Subjects With Metabolic Acidosis Associated With Chronic Kidney Disease
NCT03390842	PHASE3	COMPLETED	Long-term Safety Extension to Study TRCA-301
NCT03710291	PHASE3	TERMINATED	Evaluation of Effect of TRC101 on Progression of Chronic Kidney Disease in Subjects With Metabolic Acidosis
NCT04727528	PHASE3	TERMINATED	Study of the Effect of SZC on Serum Potassium and Serum Bicarbonate in Patients With Hyperkalemia and Metabolic Acidosis Associated With Chronic Kidney Disease
NCT05697770	PHASE3	ACTIVE_NOT_RECRUITING	SODium BICarbonate for Metabolic Acidosis in the ICU
NCT06545565	PHASE3	RECRUITING	Prevention of Metabolic Acidosis in Preterm Neonates by Replacing Sodium Chloride With Sodium Acetate in Parenteral Nutrition
NCT07355062	PHASE3	RECRUITING	A Study to Evaluate the Efficacy and Safety of Veverimer for the Treatment of Metabolic Acidosis
NCT00960232	PHASE3	COMPLETED	Vitamin D, Blood Pressure, Lipids, Infection and Depression
NCT01012414	PHASE3	TERMINATED	Effect of Vitamin D Supplement on Inflammation Markers in High-Risk Cardiovascular Patients With Chronic Kidney Disease
NCT01315366	PHASE3	COMPLETED	Hypovitaminosis D : A Link Between Bone/Mineral and Fat/Fuel Metabolism
NCT01689779	PHASE3	COMPLETED	High Dose Preoperative Cholecalciferol Supplementation and Perioperative Vitamin D Status
NCT01896544	PHASE3	COMPLETED	Cholecalciferol Supplementation for Sepsis in the ICU
NCT02328404	PHASE3	COMPLETED	The Effect of Vitamin D Supplementation Among Overweight Jordanian Women With Polycystic Ovary Syndrome (PCOS)
NCT02434380	PHASE3	COMPLETED	Effect of Vitamin D Replacement on Maternal and Neonatal Outcomes
NCT03272126	PHASE3	COMPLETED	Importance of Dosing Regimen for the Effect of Vitamin D Supplementation
NCT05306704	PHASE3	COMPLETED	High-Dose Vitamin D3 Supplementation in the Treatment of Human Immune Deficiency Virus Patients Trial
NCT05425914	PHASE3	COMPLETED	Impact of Vitamin D3 Supplementation in Non-Sjogren Dry Eye Patients With Low Serum Vitamin D Level
NCT00913796	PHASE2	COMPLETED	Metabolic Acidosis in Renal Transplant Patients
NCT02303548	PHASE2	COMPLETED	Bicarbonate in Patients With Out-of-hospital Cardiac Arrest
NCT04984226	PHASE2	RECRUITING	Sodium Bicarbonate and Mitochondrial Energetics in Persons With CKD
NCT05147051	PHASE2	COMPLETED	Meglimine Sodium Succinate for Correction of Metabolic Acidosis in Critically Ill Patients
NCT00001151	PHASE2	TERMINATED	Studies With 1,25-Dihydroxycholecalciferol
NCT00992797	PHASE2	UNKNOWN	Diabetes Intervention Trial With Vitamin D in Subjects of Nordic and Sub-Indian Ethnicity
NCT01656070	PHASE2	COMPLETED	Vitamin D Supplementation in HIV-infected Youth
NCT02452762	PHASE2	COMPLETED	Rapid Normalization of Vitamin D in Critically Ill Children: A Phase II Dose Evaluation Randomized Controlled Trial
NCT01777178	PHASE1	COMPLETED	Comparison of Standard Versus Low Bicarbonate Hemodialysis
NCT01894594	PHASE1	TERMINATED	Efficacy, Safety Study and Benefit of Alkali Therapy in Sickle Cell Disease
NCT01452412	PHASE2/PHASE3	COMPLETED	Alkali Therapy in Chronic Kidney Disease
NCT06366230	PHASE1/PHASE2	RECRUITING	Adding Urea to the Final Dialysis Fluid