CA2

Summary

CA2 (carbonic anhydrase 2, HGNC:1373) is a protein-coding gene on chromosome 8q21.2, encoding Carbonic anhydrase 2 (P00918). Catalyzes the reversible hydration of carbon dioxide.

The protein encoded by this gene is one of several isozymes of carbonic anhydrase, which catalyzes reversible hydration of carbon dioxide. Defects in this enzyme are associated with osteopetrosis and renal tubular acidosis. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 760 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive osteopetrosis 3 (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 225 total — 10 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 70
• Druggable target: yes — 89 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000067

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1373
Approved symbol	CA2
Name	carbonic anhydrase 2
Location	8q21.2
Locus type	gene with protein product
Status	Approved
Aliases	Car2, CA-II, CAII
Ensembl gene	ENSG00000104267
Ensembl biotype	protein_coding
OMIM	611492
Entrez	760

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 2 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000285379, ENST00000518231, ENST00000520127, ENST00000520996, ENST00000522742, ENST00000960030

RefSeq mRNA: 2 — MANE Select: NM_000067 NM_000067, NM_001293675

CCDS: CCDS6239

Canonical transcript exons

ENST00000285379 — 7 exons

Exon	Start	End
ENSE00000980911	85464007	85464115
ENSE00001195849	85480670	85481493
ENSE00003554549	85474324	85474416
ENSE00003577522	85477120	85477275
ENSE00003581445	85473693	85473811
ENSE00003592444	85465272	85465469
ENSE00003616575	85475798	85475860

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.0107 / max 1547.3254, expressed in 1097 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89619	37.5377	1094
89618	0.2427	102
89617	0.1412	70
89615	0.0598	6
89616	0.0294	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic mucosa	UBERON:0000317	99.88	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.86	gold quality
mucosa of transverse colon	UBERON:0004991	99.83	gold quality
rectum	UBERON:0001052	99.59	gold quality
sperm	CL:0000019	99.49	gold quality
ileal mucosa	UBERON:0000331	99.46	gold quality
trabecular bone tissue	UBERON:0002483	99.34	gold quality
jejunal mucosa	UBERON:0000399	99.15	gold quality
pylorus	UBERON:0001166	99.04	gold quality
tibia	UBERON:0000979	98.97	gold quality
duodenum	UBERON:0002114	98.96	gold quality
adult mammalian kidney	UBERON:0000082	98.59	gold quality
corpus callosum	UBERON:0002336	98.52	gold quality
renal medulla	UBERON:0000362	98.35	gold quality
choroid plexus epithelium	UBERON:0003911	98.27	gold quality
pons	UBERON:0000988	98.14	gold quality
inferior vagus X ganglion	UBERON:0005363	98.12	gold quality
bone element	UBERON:0001474	97.97	gold quality
upper leg skin	UBERON:0004262	97.84	gold quality
subthalamic nucleus	UBERON:0001906	97.80	gold quality
nephron tubule	UBERON:0001231	97.63	gold quality
putamen	UBERON:0001874	97.58	gold quality
gall bladder	UBERON:0002110	97.53	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.53	gold quality
superior vestibular nucleus	UBERON:0007227	97.52	gold quality
bone marrow	UBERON:0002371	97.46	gold quality
lateral globus pallidus	UBERON:0002476	97.31	gold quality
spinal cord	UBERON:0002240	97.05	gold quality
male germ cell	CL:0000015	96.99	gold quality
kidney	UBERON:0002113	96.89	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	2531.87
E-GEOD-125970	yes	1850.86
E-CURD-11	yes	582.67
E-MTAB-10485	yes	500.25
E-HCAD-4	yes	153.09
E-MTAB-6701	yes	80.49
E-MTAB-7316	yes	37.60
E-MTAB-10553	yes	24.78
E-GEOD-84465	yes	23.86
E-CURD-122	yes	21.62
E-MTAB-8410	yes	21.06
E-HCAD-10	yes	17.81
E-MTAB-9221	yes	13.56
E-HCAD-9	yes	11.84
E-MTAB-9388	yes	8.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, APEX1, ESR1, FOXA2, FOXO1, HNF1B, JUN, NFKB, RARB, SP1, TFAP2A, THRA, VDR

miRNA regulators (miRDB)

70 targeting CA2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
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-4760-3P	99.93	70.50	2385
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-1303	99.65	69.77	1662

Literature-anchored findings (GeneRIF, showing 40)

• Elevated serum anti-carbonic anhydrase II antibodies in patients with ulcerative colitis. (PMID:11956656)
• A new bicarbonate binding site observed in a T199P variant CAII has implications for understanding the mechanism by which the main-chain amino group of Thr199 acquired an important role for orientation of the substrate during evolution of the enzyme. (PMID:12056894)
• Data show that inserting histidine residues into the active site cavity of carbonic anhydrase II or III results in rates of proton transfer to the zinc-bound hydroxide that are antagonistic or suppressive with respect to the corresponding single mutants (PMID:12171926)
• This is the first report of a considerably stabilized variant of human CA-II, engineered with a disulfide bridge from a related and unusually stable CA form from Neisseria gonorrhoeae. (PMID:12501217)
• high prevalence of autoantibodies against human carbonic anhydrase II and lactoferrin strongly suggests the involvement of autoimmunity against the exocrine pancreas as well as the endocrine pancreas in some type 1 diabetic patients (PMID:12826902)
• data increase the minimal extent of a functionally defined carbonic anhydrase 2 binding site in anion exchanger 1 (PMID:12933803)
• concentrations in nondialyzed chronic kidney disease patients, and the relationship with acidosis, zinc, anemia, and iron supplementation (PMID:14675565)
• NBC3 and CAII interact to maximize the HCO(3)(-) transport rate. Although PKA decreased NBC3 transport activity, it did so independently of the NBC3/CAII interaction and did not involve phosphorylation of NBC3Ct. (PMID:14736710)
• The primary features in CA-II that drive deviations from the inherent metal ion affinity trend, i.e., the Irving-Williams series, are those that alter the energy required for a bound metal ion to adopt a preferred coordination number and geometry. (PMID:15049705)
• transfected Pdcd4 suppresses carbonic anhydrase type II protein expression in HEK293 and Bon-1 carcinoid cells; the translation inhibitor pdcd4 represses endocrine tumor cell growth by suppression of carbonic anhydase II (PMID:15062553)
• Results indicate that carbonic anhydrase II activity enhances flux through the sodium bicarbonate cotransporter kNBC1 when the enzyme is bound to kNBC1. (PMID:15218065)
• 11 new mutations were found in 21 patients referred for confirmation of the diagnosis of CA II deficiency. These mutations were scattered over the genome from exon 2 to 7. (PMID:15300855)
• CA II was crystallized with 667-coumate and the structure was determined by X-ray crystallography at 1.95 A (PMID:15453828)
• A water bridge consisting of two intervening water molecules is consistent with efficient proton transfer in human carbonic anhydrase II. (PMID:15667203)
• cytosolic CA I, II, and XIII are downregulated in neoplastic colorectal mucosa compared to normal colorectal mucosa (PMID:15836783)
• Inhibition by zonisimide shown at x ray crystallographic level. (PMID:15837316)
• Isothiocyanato sulfonamide thioureas inhibit this enzyme. (PMID:15837325)
• Human carbonic anhydrase II has a histidine that is directly hydrogen-bonded to the zinc-bound hydroxide, and can adopt the correct distance geometry to support proton transfer. (PMID:16106378)
• A novel c.232+1G>T mutation was identified in a consanguineous patient. The mutation disrupts the splice site at the 3’ end of exon 2 of the messenger RNA precursor. (PMID:16265785)
• a novel phosphorylation-regulated carbonic anhydrase II binding site exists in distal amino acids of the Na+/H+ exchanger tail. (PMID:16475831)
• CA II does not enhance NBCe1-A activity (PMID:16687407)
• levels and immunolocalization of carbonic anhydrase II in the developing and adult human brain; findings suggest the possible involvement of CA II in a wide spectrum of biologic processes in the developing and adult brain (PMID:16825953)
• The redesign increased the catalytic rates of CA II for substrates with long acyl chains by removal of steric hinders and addition of new favourable binding interactions. (PMID:16996812)
• Tautomerization of His(64) mediates the transfers of both protons and water molecules at a neutral pH with high efficiency, requiring no time- or energy-consuming processes, and suggesting a catalytic mechanism for the enzyme. (PMID:17202139)
• On the basis of the comparative study of the molecular dynamics simulation results, the HCA II crystal structure observed is most likely in the Zn-bound water/His64 state. (PMID:17319692)
• free energy profile for His64 suggests that it adopts an “in” orientation for hydration, which brings Ndelta close to catalytic Zn. When His is protonated, it rotates to an “out” orientation, a more favorable solvation environment for protonated His64. (PMID:17319695)
• relative overexpression of CA II as initially found by microarray analysis of AD and psoriasis skin is probably due to differences in cytokine environment (PMID:17363915)
• demonstrate cross-reactivity of this osteoprotegerin antibody in western blots (PMID:17631639)
• No mutation was found in the coding regions and intron-exon boundaries of the genes for CA II, CA IV, CA XIV, kNCB1, NHE3, NHE8, NHRF1, NHRF2 and SLC26A6 amplified from genomic DNA of family members with pRTA. (PMID:17881426)
• Results herein suggested that the correct positioning of the long loop around P237 might be crucial to the folding of HCA II, particularly the formation of the active site. (PMID:18060825)
• Immunoblot analyses showed that the levels of carbonic anhydrase II are increased in the brain of infants and young children with Down’s syndrome. (PMID:18083150)
• study found the thermodynamic stability of the HCA II mutants was in the following order: HCA IIpwt > H107N > E117A > H107A > H107F > H107Y > H107N/E117A > H107A/E117A (PMID:18189416)
• electrostatics rather than the orientation of the acceptor. (PMID:18247480)
• structure of carbonic anhydrase II was solved by the molecular-replacement method (PMID:18323598)
• the effective movement of H(+) into the bulk cytosol is increased by CAII, thus slowing the dissipation of the H(+) gradient across the cell membrane, which drives MCT1 activity (PMID:18539591)
• Suggest that detection of carbonic anhydrase II antibody may be useful in the differential diagnosis of autoimmune pancreatitis and pancreatic cancer. (PMID:18580434)
• the roles of the residues of the hydrophilic side of the active site cavity in maintaining efficient catalysis by carbonic anhydrase II. (PMID:18942852)
• DNA sequences of all 37 hpbetaCA clones encoded a 221 amino acid polypeptide with a variety of polymorphisms (57 types of amino acid substitution at 48 residue positions). There was no polymorphism functionally relevant to the gastric lesion type. (PMID:19012038)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• anti-CAII autoantibodies provoke pathogenic effects on retinal cells by decreasing cell survival by blocking the CAII cellular functions (PMID:19269136)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cahz	ENSDARG00000011166
danio_rerio	ca2	ENSDARG00000014488
mus_musculus	Car2	ENSMUSG00000027562
rattus_norvegicus	Car2	ENSRNOG00000009629
drosophila_melanogaster	CAH1	FBGN0027844

Paralogs (14): CA11 (ENSG00000063180), CA12 (ENSG00000074410), CA9 (ENSG00000107159), CA14 (ENSG00000118298), CA6 (ENSG00000131686), CA1 (ENSG00000133742), CA10 (ENSG00000154975), CA3 (ENSG00000164879), CA4 (ENSG00000167434), CA7 (ENSG00000168748), CA5B (ENSG00000169239), CA5A (ENSG00000174990), CA8 (ENSG00000178538), CA13 (ENSG00000185015)

Protein

Protein identifiers

Carbonic anhydrase 2 — P00918 (reviewed: P00918)

Alternative names: Carbonate dehydratase II, Carbonic anhydrase C, Carbonic anhydrase II, Cyanamide hydratase CA2

All UniProt accessions (4): E5RID5, E5RK37, P00918, V9HW21

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible hydration of carbon dioxide. Can also hydrate cyanamide to urea. Stimulates the chloride-bicarbonate exchange activity of SLC26A6. Essential for bone resorption and osteoclast differentiation. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption.

Subunit / interactions. Interacts with SLC4A4. Interaction with SLC4A7 regulates SLC4A7 transporter activity. Interacts with SLC26A6 isoform 4 (via C-terminus cytoplasmic domain).

Subcellular location. Cytoplasm. Cell membrane.

Disease relevance. Osteopetrosis, autosomal recessive 3 (OPTB3) [MIM:259730] A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by X-ray, histamine, L-adrenaline, L- and D-phenylalanine, L- and D-histidine, L-His-OMe and beta-Ala-His (carnosine). Competitively inhibited by saccharin, thioxolone, coumarins, 667-coumate, celecoxib (Celebrex), valdecoxib (Bextra), SC-125, SC-560, diclofenac, acetate, azide, bromide, sulfonamide derivatives such as acetazolamide (AZA), methazolamide (MZA), ethoxzolamide (EZA), dichlorophenamide (DCP), brinzolamide, dansylamide, thiabendazole-5-sulfonamide, trifluoromethane sulfonamide and N-hydroxysulfamide, fructose-based sugar sulfamate RWJ-37497, and Foscarnet (phosphonoformate trisodium salt). Repressed strongly by hydrogen sulfide(HS) and weakly by nitrate (NO(3)). Esterase activity weakly reduced by cyanamide. N-hydroxyurea interferes with zinc binding and inhibit activity.

Cofactor. Zinc. Can also use cobalt(II) with lower efficiency, but not copper(II), nickel(II) and manganese(II).

Miscellaneous. Target of drugs used in treatments against glaucoma disorder and breast cancer.

Similarity. Belongs to the alpha-carbonic anhydrase family.

RefSeq proteins (2): NP_000058, NP_001280604 (=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 (98 total): mutagenesis site 37, strand 23, helix 9, sequence variant 7, turn 5, site 4, modified residue 4, binding site 4, initiator methionine 1, chain 1, domain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1241 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3K34	X-RAY DIFFRACTION	0.9
3KS3	X-RAY DIFFRACTION	0.9
5Y2S	X-RAY DIFFRACTION	0.9
6B00	X-RAY DIFFRACTION	0.9
6KLZ	X-RAY DIFFRACTION	0.9
6KM2	X-RAY DIFFRACTION	0.9
6ROB	X-RAY DIFFRACTION	0.93
3U7C	X-RAY DIFFRACTION	0.93
6KM0	X-RAY DIFFRACTION	0.93
6ROE	X-RAY DIFFRACTION	0.94
6SBL	X-RAY DIFFRACTION	0.94
6RH4	X-RAY DIFFRACTION	0.95
1LUG	X-RAY DIFFRACTION	0.95
6RQI	X-RAY DIFFRACTION	0.95
6S9Z	X-RAY DIFFRACTION	0.95
6SAY	X-RAY DIFFRACTION	0.95
6SBH	X-RAY DIFFRACTION	0.95
6SBM	X-RAY DIFFRACTION	0.95
6YZN	X-RAY DIFFRACTION	0.95
6RKN	X-RAY DIFFRACTION	0.96
4YXI	X-RAY DIFFRACTION	0.96
6RFH	X-RAY DIFFRACTION	0.97
4FPT	X-RAY DIFFRACTION	0.98
4FRC	X-RAY DIFFRACTION	0.98
4FU5	X-RAY DIFFRACTION	0.98
6SG6	X-RAY DIFFRACTION	0.98
6T81	X-RAY DIFFRACTION	0.98
7OYM	X-RAY DIFFRACTION	0.98
7OYN	X-RAY DIFFRACTION	0.98
2FOU	X-RAY DIFFRACTION	0.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00918-F1	97.38	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 (5): 67 (fine-tunes the proton-transfer properties of h-64; involved in the binding of some activators, including histamine and l-histidine); 92 (involved in the binding of some activators, including histamine and l-histidine); 64 (proton donor/acceptor); 7 (fine-tunes the proton-transfer properties of h-64); 62 (fine-tunes the proton-transfer properties of h-64; involved in the binding of some activators, including histamine and l-histidine)

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

Post-translational modifications (4): 2, 2, 165, 172

Mutagenesis-validated functional residues (37):

Position	Phenotype
5	impaired activity, not rescued by 4-methylimidazole (4-mi); when associated with w-64.
7	enhanced activity.
7	reduced proton transfer rate.
62	reduced activity.
62	strongly reduced activity.
62	reduced proton transfer; when associated with a-64.
64	reduced co(2) hydrase activity, rescued by 4-methylimidazole (4-mi). reduced proton transfer; when associated with h-62.
64	impaired activity, not rescued by 4-methylimidazole (4-mi).
64	impaired activity, rescued by 4-methylimidazole (4-mi). impaired activity, not rescued by 4-methylimidazole (4-mi); when
65	reduced activity.
65	2-fold decrease in enzyme efficiency, as determined by kcat/km ratio, and efficiently inhibited by chlorzolamide; when a
67	enhanced proton transfer; when associated with a-64.
67	reduced activity.
67	2-fold decrease in enzyme efficiency, as determined by kcat/km ratio, and efficiently inhibited by chlorzolamide; when a
94	strongly reduced co(2) hydrase and p-nitrophenyl acetate esterase activities, impaired stability of zinc binding.
106	strongly reduced co(2) hydrase activity.
106	normal co(2) hydrase activity.
117	strongly reduced activity and sulfonamide affinity.
119	reduced activity.
119	strongly reduced activity.
121	reduced co(2) hydrase and p-nitrophenyl acetate esterase activities.
121	strongly reduced co(2) hydrase and p-nitrophenyl acetate esterase activities.

Function

Pathways and Gene Ontology

Reactome pathways

7 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-9925563	Developmental Lineage of Pancreatic Ductal Cells
R-HSA-1430728	Metabolism
R-HSA-1480926	O2/CO2 exchange in erythrocytes
R-HSA-382551	Transport of small molecules

MSigDB gene sets: 586 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, ELVIDGE_HYPOXIA_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, LEE_NEURAL_CREST_STEM_CELL_DN, GNF2_PRDX2, GOMF_CARBONATE_DEHYDRATASE_ACTIVITY, JAEGER_METASTASIS_DN, GOBP_RESPONSE_TO_ANGIOTENSIN, MAHADEVAN_IMATINIB_RESISTANCE_DN, TGACCTY_ERR1_Q2, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, CHX10_01, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT

GO Biological Process (11): morphogenesis of an epithelium (GO:0002009), carbon dioxide transport (GO:0015670), positive regulation of synaptic transmission, GABAergic (GO:0032230), obsolete positive regulation of cellular pH reduction (GO:0032849), angiotensin-activated signaling pathway (GO:0038166), regulation of monoatomic anion transport (GO:0044070), secretion (GO:0046903), regulation of intracellular pH (GO:0051453), neuron cellular homeostasis (GO:0070050), positive regulation of dipeptide transmembrane transport (GO:2001150), regulation of chloride transport (GO:2001225)

GO Molecular Function (7): arylesterase activity (GO:0004064), carbonate dehydratase activity (GO:0004089), zinc ion binding (GO:0008270), cyanamide hydratase activity (GO:0018820), protein binding (GO:0005515), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), myelin sheath (GO:0043209), apical part of cell (GO:0045177), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
O2/CO2 exchange in erythrocytes	2
Metabolism	1
Developmental Cell Lineages of the Exocrine Pancreas	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
hydro-lyase activity	2
tissue morphogenesis	1
epithelium development	1
gas transport	1
one-carbon compound transport	1
regulation of synaptic transmission, GABAergic	1
positive regulation of synaptic transmission	1
synaptic transmission, GABAergic	1
G protein-coupled receptor signaling pathway	1
cellular response to angiotensin	1
monoatomic anion transport	1
regulation of monoatomic ion transport	1
transport	1
regulation of pH	1
intracellular monoatomic cation homeostasis	1
regulation of biological quality	1
cellular homeostasis	1
positive regulation of transmembrane transport	1
dipeptide transmembrane transport	1
positive regulation of dipeptide transport	1
regulation of dipeptide transmembrane transport	1
chloride transport	1
regulation of monoatomic anion transport	1
carboxylic ester hydrolase activity	1
transition metal ion binding	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

2332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CA2	SLC9A1	P19634	938
CA2	SLC4A4	Q9Y6R1	880
CA2	TCIRG1	Q13488	869
CA2	ATP6V1B1	P15313	839
CA2	H7C2H4	H7C2H4	820
CA2	P0DN79	P0DN79	820
CA2	CLCN7	P51798	804
CA2	ATP4A	P20648	797
CA2	OSTM1	Q86WC4	795
CA2	CYP24A1	Q07973	792
CA2	ATP12A	P54707	792
CA2	CTSK	P43235	791
CA2	SLC4A7	Q9Y6M7	783
CA2	PLEKHM1	Q9Y4G2	777
CA2	SLC9A3	P48764	756

IntAct

30 interactions, top by confidence:

A	B	Type	Score
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
VPS35	SPAG9	psi-mi:“MI:0914”(association)	0.530
Cdk1		psi-mi:“MI:0915”(physical association)	0.400
PCNA	CA2	psi-mi:“MI:0915”(physical association)	0.400
CA2		psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
USP42	KPNA3	psi-mi:“MI:0914”(association)	0.350
Vav2	CALU	psi-mi:“MI:0914”(association)	0.350
ARHGAP26	NUDT21	psi-mi:“MI:0914”(association)	0.350
KDM4C	SMCHD1	psi-mi:“MI:0914”(association)	0.350
NEK8	TGM5	psi-mi:“MI:0914”(association)	0.350
MAPT	SEPTIN8	psi-mi:“MI:0914”(association)	0.350
NEK10	GPATCH4	psi-mi:“MI:0914”(association)	0.350
PKP2	A2ML1	psi-mi:“MI:0914”(association)	0.350
RBPMS	CA2	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
SLC22A6	CLGN	psi-mi:“MI:0914”(association)	0.350
SLC37A2	WWP2	psi-mi:“MI:0914”(association)	0.350
SLC41A1	FADS2	psi-mi:“MI:0914”(association)	0.350
SLC8A3	EXTL3	psi-mi:“MI:0914”(association)	0.350
SV2C	TIMM23	psi-mi:“MI:0914”(association)	0.350
SLC5A2	CA2	psi-mi:“MI:0914”(association)	0.350
METTL6	EIF3F	psi-mi:“MI:0914”(association)	0.350
DISP3	CA2	psi-mi:“MI:0915”(physical association)	0.000
ANKZF1	CA2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (92): CA2 (Affinity Capture-MS), CA2 (Affinity Capture-MS), CA2 (Proximity Label-MS), CA2 (Affinity Capture-MS), CA2 (Affinity Capture-MS), CA2 (Affinity Capture-MS), SLC4A8 (Reconstituted Complex), CA2 (Proximity Label-MS), CA2 (Affinity Capture-MS), ACOT1 (Co-fractionation), CA2 (Affinity Capture-MS), CA2 (Affinity Capture-MS), CA2 (Affinity Capture-MS), SLC9A1 (Reconstituted Complex), SLC9A1 (Affinity Capture-Western)

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

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	10
Uncertain significance	96
Likely benign	66
Benign	24

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
1454475	NC_000008.10:g.(?86376311)(86377718_?)del	Pathogenic
288909	NM_000067.3(CA2):c.232+1G>A	Pathogenic
4292335	NM_000067.3(CA2):c.381T>G (p.Tyr127Ter)	Pathogenic
632526	NM_000067.3(CA2):c.143_146del (p.Ser48fs)	Pathogenic
914	NM_000067.3(CA2):c.52A>G (p.Lys18Glu)	Pathogenic
915	NM_000067.3(CA2):c.707C>A (p.Pro236His)	Pathogenic
916	NM_000067.3(CA2):c.319C>T (p.His107Tyr)	Pathogenic
917	NM_000067.3(CA2):c.508-1G>C	Pathogenic
919	NM_000067.3(CA2):c.120T>G (p.Tyr40Ter)	Pathogenic
920	NM_000067.3(CA2):c.621del (p.Trp208fs)	Pathogenic
1700071	NM_000067.3(CA2):c.2T>G (p.Met1Arg)	Likely pathogenic
2636443	NM_000067.3(CA2):c.232+2T>G	Likely pathogenic
3036420	NM_000067.3(CA2):c.153T>A (p.Tyr51Ter)	Likely pathogenic
3595893	NM_000067.3(CA2):c.165_166insGAGGA (p.Ser56fs)	Likely pathogenic
3595900	NM_000067.3(CA2):c.233-1G>A	Likely pathogenic
3595901	NM_000067.3(CA2):c.314C>G (p.Ser105Ter)	Likely pathogenic
3595904	NM_000067.3(CA2):c.445-2_445-1delinsTC	Likely pathogenic
3595915	NM_000067.3(CA2):c.672del (p.Lys224fs)	Likely pathogenic
804410	NM_000067.3(CA2):c.579C>G (p.Tyr193Ter)	Likely pathogenic
973759	NM_000067.3(CA2):c.275A>C (p.Gln92Pro)	Likely pathogenic

SpliceAI

932 predictions. Top by Δscore:

Variant	Effect	Δscore
8:85465268:CCA:C	acceptor_loss	1.0000
8:85465269:CAG:C	acceptor_loss	1.0000
8:85465270:A:AG	acceptor_gain	1.0000
8:85465270:AG:A	acceptor_gain	1.0000
8:85465270:AGGAC:A	acceptor_loss	1.0000
8:85465271:G:GG	acceptor_gain	1.0000
8:85465271:GG:G	acceptor_gain	1.0000
8:85465271:GGA:G	acceptor_gain	1.0000
8:85465271:GGAC:G	acceptor_gain	1.0000
8:85465466:GCAG:G	donor_gain	1.0000
8:85465468:AGG:A	donor_loss	1.0000
8:85465470:G:GG	donor_gain	1.0000
8:85465470:GTC:G	donor_loss	1.0000
8:85465471:T:A	donor_loss	1.0000
8:85473355:T:TA	acceptor_gain	1.0000
8:85473691:A:AG	acceptor_gain	1.0000
8:85473692:G:GG	acceptor_gain	1.0000
8:85473809:GAA:G	donor_gain	1.0000
8:85473812:G:GG	donor_gain	1.0000
8:85475796:A:AG	acceptor_gain	1.0000
8:85475796:A:AT	acceptor_loss	1.0000
8:85475796:AG:A	acceptor_gain	1.0000
8:85475796:AGGTT:A	acceptor_gain	1.0000
8:85475797:G:GA	acceptor_gain	1.0000
8:85475797:GG:G	acceptor_gain	1.0000
8:85475797:GGTT:G	acceptor_gain	1.0000
8:85475797:GGTTG:G	acceptor_gain	1.0000
8:85475857:AAAGG:A	donor_loss	1.0000
8:85475858:AAGG:A	donor_loss	1.0000
8:85475859:AGGTA:A	donor_loss	1.0000

AlphaMissense

1717 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:85473746:C:G	H96D	0.997
8:85473777:A:T	E106V	0.995
8:85477234:T:A	W208R	0.995
8:85477234:T:C	W208R	0.995
8:85480739:C:A	R245S	0.995
8:85474325:T:C	L118P	0.994
8:85473740:C:G	H94D	0.993
8:85477198:T:C	S196P	0.993
8:85465285:G:C	W16C	0.992
8:85465285:G:T	W16C	0.992
8:85473748:C:A	H96Q	0.992
8:85473748:C:G	H96Q	0.992
8:85473749:T:A	W97R	0.992
8:85473749:T:C	W97R	0.992
8:85474327:C:G	H119D	0.992
8:85477202:T:C	L197P	0.992
8:85465283:T:A	W16R	0.991
8:85465283:T:C	W16R	0.991
8:85473746:C:A	H96N	0.991
8:85477196:G:A	G195D	0.991
8:85477205:C:T	T198I	0.991
8:85465326:C:A	P30H	0.990
8:85465329:T:A	V31D	0.990
8:85477236:G:C	W208C	0.990
8:85477236:G:T	W208C	0.990
8:85480740:G:C	R245P	0.990
8:85480765:G:C	R253S	0.990
8:85480765:G:T	R253S	0.990
8:85473778:G:C	E106D	0.989
8:85473778:G:T	E106D	0.989

dbSNP variants (sampled 300 via entrez): RS1000051731 (8:85462106 A>C,T), RS1000472997 (8:85479564 G>A,C), RS1001064032 (8:85475053 A>T), RS1001069168 (8:85467088 C>T), RS1001101818 (8:85481478 A>G), RS1001418783 (8:85466683 C>T), RS1001609643 (8:85469294 G>C), RS1001745282 (8:85478506 A>G), RS1001757829 (8:85463125 A>C), RS1001786944 (8:85465544 A>G), RS1001789130 (8:85462830 A>T), RS1001841269 (8:85470148 G>A), RS1001892006 (8:85470593 T>A,G), RS1001975274 (8:85469752 A>T), RS1002023593 (8:85476768 A>T)

Disease associations

OMIM: gene MIM:611492 | disease phenotypes: MIM:259730

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive osteopetrosis 3	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
autosomal recessive osteopetrosis 3	Definitive	AR

Mondo (2): autosomal recessive osteopetrosis 3 (MONDO:0009818), osteopetrosis (MONDO:0017198)

Orphanet (2): Osteopetrosis with renal tubular acidosis (Orphanet:2785), Osteopetrosis and related disorders (Orphanet:2781)

HPO phenotypes

70 total (30 of 70 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000126	Hydronephrosis
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000179	Thick lower lip vermilion
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000278	Retrognathia
HP:0000347	Micrognathia
HP:0000400	Macrotia
HP:0000405	Conductive hearing impairment
HP:0000479	Abnormal retinal morphology
HP:0000505	Visual impairment
HP:0000572	Visual loss
HP:0000592	Blue sclerae
HP:0000648	Optic atrophy
HP:0000689	Dental malocclusion
HP:0000692	Tooth malposition
HP:0000767	Pectus excavatum
HP:0000787	Nephrolithiasis
HP:0000867	Secondary hyperparathyroidism
HP:0001105	Retinal atrophy
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001293	Cranial nerve compression
HP:0001328	Specific learning disability
HP:0001357	Plagiocephaly
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001562	Oligohydramnios

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002040_1	Blood trace element (Zn levels)	6.000000e-12

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D010022	Osteopetrosis	C05.116.099.708.702.678
C536058	Osteopetrosis with renal tubular acidosis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL205 (SINGLE PROTEIN), CHEMBL2095180 (PROTEIN FAMILY), CHEMBL2096906 (SELECTIVITY GROUP), CHEMBL5465206 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

89 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 5,640,753 (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
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1054	TRICHLORMETHIAZIDE	4	11,619
CHEMBL1055	CHLORTHALIDONE	4	20,442
CHEMBL1072	BUMETANIDE	4	22,087
CHEMBL112	ACETAMINOPHEN	4	157,242
CHEMBL1161681	NITROUS ACID	4	286,808
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1200679	ZINC CHLORIDE	4	411,454
CHEMBL121	ROSIGLITAZONE	4	58,849
CHEMBL1235452	SULFUR	4	2,163,993
CHEMBL1286	LEVETIRACETAM	4	13,997
CHEMBL1356	SODIUM BENZOATE	4	244,527
CHEMBL14060	PHENOL	4	1,871,332
CHEMBL1684	BENDROFLUMETHIAZIDE	4	14,097
CHEMBL17	DICHLORPHENAMIDE	4	9,022
CHEMBL18	ETHOXZOLAMIDE	4	3,042
CHEMBL19	METHAZOLAMIDE	4	65
CHEMBL20	ACETAZOLAMIDE	4	28,768
CHEMBL21	SULFANILAMIDE	4	153,075
CHEMBL2105581	VERALIPRIDE	4	1,165
CHEMBL218490	DORZOLAMIDE	4
CHEMBL220491	BRINZOLAMIDE	4
CHEMBL220492	TOPIRAMATE	4
CHEMBL255863	NILOTINIB	4
CHEMBL26	SULPIRIDE	4
CHEMBL325041	BORTEZOMIB	4
CHEMBL328560	SULTHIAME	4
CHEMBL35	FUROSEMIDE	4
CHEMBL406	INDAPAMIDE	4
CHEMBL408	TROGLITAZONE	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 (5 total), top 5:

Ligand	Action	Affinity	Parameter
compound 11 [PMID: 41150938]	Inhibition	8.13	pKi
compound 5a [PMID: 31287314]	Inhibition	7.02	pKi
compound 5b [PMID: 31287314]	Inhibition	6.67	pKi
pyrogallol	Inhibition	6.27	pKi
salvianolic acid A	Inhibition	5.02	pKi

Binding affinities (BindingDB)

714 measured of 958 human assays (1052 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
3-{[(2-methoxyethyl)(3-methoxypropyl)amino]methyl}-2-methyl-1,1-dioxo-2H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide hydrochloride	KI	0.08 nM
2-(3-methoxyphenyl)-1,1-dioxo-2H,3H,4H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide	KD	0.1 nM
(4R)-2-(3-methoxyphenyl)-4-(methylamino)-1,1-dioxo-2H,3H,4H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide	KD	0.1 nM
2-(3-methoxyphenyl)-1,1-dioxo-2H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide	KD	0.13 nM
4-hydroxy-2-(4-methoxyphenyl)-1,1-dioxo-2H,3H,4H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide	KD	0.16 nM
4-hydroxy-1,1-dioxo-2-(thiophen-2-ylmethyl)-2H,3H,4H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide	KD	0.2 nM
2-[(2E)-4-(morpholin-4-yl)but-2-en-1-yl]-1,1-dioxo-2H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide hydrochloride	KI	0.24 nM
(4R)-4-(ethylamino)-2-(2-methoxyethyl)-1,1-dioxo-2H,3H,4H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide	KD	0.32 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
2-N-[(4-methylphenyl)methyl]thiophene-2,5-disulfonamide	KD	0.46 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
2-N-[(4-methoxyphenyl)methyl]thiophene-2,5-disulfonamide	KD	0.49 nM
4-{(4-bromophenyl)methylamino}benzonitrile	IC50	0.5 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
2-(3-hydroxyphenyl)-1,1-dioxo-3-[(prop-2-yn-1-ylamino)methyl]-2H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide hydrochloride	IC50	0.6 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
2000-07790	IC50	0.62 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
Compound 17g1	IC50	0.79 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
5-(thiophene-2-sulfonyl)thiophene-2-sulfonamide	IC50	0.81 nM
YM511-based dual aromatase-sulfatase inhibitor (DASI) 7	IC50	0.82 nM
Compound 5b	IC50	0.82 nM
2-N-(thiophen-2-ylmethyl)thiophene-2,5-disulfonamide	KD	0.83 nM
5-(thiophen-2-ylsulfanyl)thiophene-2-sulfonamide	IC50	0.89 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxypropanamide	KI	0.9 nM
2-{2-[bis(2-methoxyethyl)amino]ethyl}-1,1-dioxo-2H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide hydrochloride	IC50	0.91 nM
Compound 5c	IC50	0.96 nM
Compound 17b4	IC50	0.96 nM
3-(morpholin-4-ylmethyl)-1,1-dioxo-2-(prop-2-en-1-yl)-2H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide	IC50	0.99 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
2-Ethyl-3-[[bis(2-methoxyethyl)amino]methyl]-2H-thieno-[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide hydrochloride	IC50	1.04 nM
Compound 17m1	IC50	1.05 nM
5-(4-Amino-3,5-dichlorobenzenesulfonamido)-1,3,4-thiadiazole-2-sulfonamide	KI	1.1 nM
Compound 17a7	IC50	1.11 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	CHEMBL3608871
11.00	Ki	0.01	nM	CHEMBL3608881
11.00	Ki	0.01	nM	CHEMBL3608883
11.00	Ki	0.01	nM	CHEMBL3608887
11.00	Ki	0.01	nM	CHEMBL3608888
11.00	Ki	0.01	nM	CHEMBL3608890
11.00	Ki	0.01	nM	CHEMBL3608892
11.00	Kd	0.01	nM	CHEMBL4451500
10.96	Kd	0.011	nM	CHEMBL4176862
10.96	Kd	0.011	nM	CHEMBL4461481
10.85	Kd	0.014	nM	CHEMBL4516858
10.80	Kd	0.016	nM	CHEMBL4473602
10.74	Kd	0.018	nM	CHEMBL4170371
10.74	Kd	0.018	nM	CHEMBL4464359
10.74	Kd	0.018	nM	CHEMBL4539340
10.70	Ki	0.02	nM	CHEMBL3608872
10.70	Ki	0.02	nM	CHEMBL3608889
10.70	Ki	0.02	nM	CHEMBL3608893
10.70	Kd	0.02	nM	CHEMBL4475496
10.70	Kd	0.02	nM	CHEMBL4475073
10.70	Kd	0.02	nM	CHEMBL4574321
10.70	Kd	0.02	nM	CHEMBL4450456
10.70	Kd	0.02	nM	CHEMBL4572161
10.70	Kd	0.02	nM	CHEMBL4562296
10.70	Kd	0.02	nM	CHEMBL4436290
10.70	Kd	0.02	nM	CHEMBL4558287
10.70	Kd	0.02	nM	CHEMBL4573963
10.66	Kd	0.022	nM	CHEMBL4168966
10.55	Kd	0.028	nM	CHEMBL4555622
10.55	Kd	0.028	nM	CHEMBL4475315
10.52	Ki	0.03	nM	CHEMBL3608894
10.52	Kd	0.03	nM	CHEMBL4516072
10.52	Kd	0.03	nM	CHEMBL4553790
10.52	Kd	0.03	nM	CHEMBL4446052
10.52	Kd	0.03	nM	CHEMBL4450306
10.52	Kd	0.03	nM	CHEMBL4517317
10.52	Ki	0.03	nM	CHEMBL4527427
10.52	Ki	0.03	nM	CHEMBL1271639
10.51	Kd	0.031	nM	CHEMBL4463683
10.51	Kd	0.031	nM	CHEMBL4441730
10.47	Kd	0.034	nM	CHEMBL3415380
10.46	Kd	0.035	nM	CHEMBL4163518
10.40	Kd	0.04	nM	CHEMBL4565224
10.40	Kd	0.04	nM	CHEMBL4470832
10.40	Kd	0.04	nM	CHEMBL4437818
10.40	Ki	0.04	nM	CHEMBL4579554
10.40	Ki	0.04	nM	CHEMBL5570465
10.37	Kd	0.043	nM	DORZOLAMIDE
10.37	Kd	0.043	nM	CHEMBL4567746
10.37	Kd	0.043	nM	CHEMBL4439634

PubChem BioAssay actives

4667 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-(2,5-dimethoxyphenyl)ethylsulfamoyl]carbamate	1231567: Inhibition of esterase activity of carbonic anhydrase 2 in human erythrocytes using PNF as substrate by spectrophotometer analysis	ki	<0.0001	uM
4-(2-cyclopropyl-1,3-oxazol-5-yl)benzenesulfonamide	1242116: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
4-(2-cyclobutyl-1,3-oxazol-5-yl)benzenesulfonamide	1242116: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
4-[2-(pyrrolidine-1-carbonyl)-1,3-oxazol-5-yl]benzenesulfonamide	1242116: Inhibition of human recombinant carbonic anhydrase 2 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	1242116: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
2-methyl-5-[2-(pyrrolidine-1-carbonyl)-1,3-oxazol-5-yl]benzenesulfonamide	1242116: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
2-methoxy-5-[2-(pyrrolidine-1-carbonyl)-1,3-oxazol-5-yl]benzenesulfonamide	1242116: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
5-(2-cyclobutyl-1,3-oxazol-5-yl)thiophene-2-sulfonamide	1242116: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
5-[2-(pyrrolidine-1-carbonyl)-1,3-oxazol-5-yl]thiophene-2-sulfonamide	1242116: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
5-[2-(morpholine-4-carbonyl)-1,3-oxazol-5-yl]thiophene-2-sulfonamide	1242116: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
4-(2-methyl-1,3-oxazol-5-yl)thiophene-2-sulfonamide	1242116: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
4-(2-cyclobutyl-1,3-oxazol-5-yl)thiophene-2-sulfonamide	1242116: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
4-[2-(pyrrolidine-1-carbonyl)-1,3-oxazol-5-yl]thiophene-2-sulfonamide	1242116: Inhibition of human recombinant carbonic anhydrase 2 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	1242116: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	ki	<0.0001	uM
2-benzylsulfanyl-N-butyl-4-chloro-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
methyl 4-[(2-benzylsulfanyl-4-chloro-5-sulfamoylbenzoyl)amino]butanoate	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-butyl-2-cyclohexylsulfanyl-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzylamino)-N-butyl-4-chloro-5-sulfamoylbenzamide	1361382: Binding affinity to recombinant full-length human carbonic anhydrase 2 expressed in Escherichia coli assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzylamino)-4-chloro-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1361382: Binding affinity to recombinant full-length human carbonic anhydrase 2 expressed in Escherichia coli assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-N-(3-hydroxypropyl)-2-phenylsulfanyl-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-benzylsulfanyl-4-bromo-N-butyl-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-benzyl-2-(benzylamino)-4-chloro-5-sulfamoylbenzamide	1361382: Binding affinity to recombinant full-length human carbonic anhydrase 2 expressed in Escherichia coli assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-butyl-2-phenylsulfanyl-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-butyl-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-butyl-4-chloro-2-phenylsulfanyl-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-butyl-4-chloro-2-cyclohexylsulfonyl-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-N-(2-methoxyethyl)-2-phenylsulfanyl-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzenesulfonyl)-N-benzyl-4-chloro-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-butyl-4-chloro-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzylamino)-4-chloro-N-(2-methoxyethyl)-5-sulfamoylbenzamide	1361382: Binding affinity to recombinant full-length human carbonic anhydrase 2 expressed in Escherichia coli assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-cyclohexylsulfanyl-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-benzyl-4-chloro-2-cyclohexylsulfonyl-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-benzylsulfanyl-4-chloro-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzylamino)-4-chloro-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1361382: Binding affinity to recombinant full-length human carbonic anhydrase 2 expressed in Escherichia coli assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
N-benzyl-4-chloro-2-phenylsulfanyl-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-cyclohexylsulfanyl-N-(2-methoxyethyl)-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-benzyl-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-butyl-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-cyclohexylsulfonyl-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1520080: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
1-(4-chlorosulfonyl-3,5-dimethylphenyl)-5-oxopyrrolidine-3-carboxylic acid	1763393: Inhibition of human recombinant CA2 assessed as intrinsic dissociation constant by thermal shift assay	kd	<0.0001	uM
1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-N-[(E)-(4-methoxyphenyl)methylideneamino]-5-oxopyrrolidine-3-carboxamide	1515315: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	<0.0001	uM
1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-N-(3,5-dimethylpyrazol-1-yl)-5-oxopyrrolidine-3-carboxamide	1515315: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	<0.0001	uM
N-[(E)-benzylideneamino]-1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxamide	1515315: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	<0.0001	uM
1-[[1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carbonyl]amino]-3-phenylthiourea	1515315: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	<0.0001	uM
methyl 1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxylate	1515315: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	<0.0001	uM
N-[(E)-benzylideneamino]-5-oxo-1-(4-sulfamoylphenyl)pyrrolidine-3-carboxamide	1515315: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	<0.0001	uM
N-[(E)-(4-bromophenyl)methylideneamino]-1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxamide	1515315: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	<0.0001	uM
3-chloro-4-[4-(3,5-dimethylpyrazole-1-carbonyl)-2-oxopyrrolidin-1-yl]-2,6-dimethylbenzenesulfonamide	1515315: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	<0.0001	uM
4-(4-methyl-1-oxophthalazin-2-yl)benzenesulfonamide	1593070: Inhibition of human cytosolic CA 2 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay	ki	<0.0001	uM
3-chloro-2,6-dimethyl-4-[2-oxo-4-(4-phenyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]benzenesulfonamide	1515315: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	<0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetazolamide	decreases activity, decreases reaction, affects binding	17
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	5
Valproic Acid	affects expression, increases expression, increases methylation	5
bisphenol A	decreases methylation, increases expression, affects cotreatment, decreases expression	4
Progesterone	affects cotreatment, decreases expression, increases expression	4
sodium arsenite	increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
Genistein	increases expression	3
nickel sulfate	decreases expression	2
seocalcitol	affects cotreatment, increases expression	2
Celecoxib	affects binding, decreases activity	2
Topiramate	affects binding, decreases activity	2
Benzo(a)pyrene	increases expression	2
Calcitriol	increases expression	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Indomethacin	affects cotreatment, decreases expression, decreases activity, decreases reaction, increases activity	2
Lead	affects expression, decreases activity	2
Methazolamide	affects binding, decreases activity	2
Pyrimidines	decreases activity	2
Silicon Dioxide	decreases expression, increases expression	2
Tretinoin	increases expression, increases activity	2
Aflatoxin B1	affects expression, decreases methylation	2
aristolochic acid I	increases expression	1
brilliant black 1	decreases activity	1
bisphenol F	affects cotreatment, decreases expression	1
SLC-0111	affects binding	1
3-methylpentyl(4-sulphamoylphenyl)carbamate	decreases activity	1
sulfamidochrysoidine	affects binding, decreases activity	1
thiosemicarbazide	decreases activity	1
triphenyl phosphate	affects expression	1

ChEMBL screening assays

1226 unique, capped per target: 1183 binding, 35 admet, 8 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002070	Binding	Inhibition of human carbonic anhydrase 2 esterase activity by spectrophotometry	In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. — Bioorg Med Chem
CHEMBL4013795	ADMET	Inhibition of recombinant human carbonic anhydrase 2 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
CHEMBL657918	Functional	Inhibitory activity of compound against human carbonic anhydrase II	Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the antipsychotic drug sulpiride. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2TB	Abcam HEK293T CA2 KO	Transformed cell line	Female
CVCL_SG41	HAP1 CA2 (-) 1	Cancer cell line	Male
CVCL_SG42	HAP1 CA2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004402	PHASE3	COMPLETED	Phase III Randomized Study of Interferon Gamma in Children With Severe, Congenital Osteopetrosis
NCT00638820	PHASE2	TERMINATED	Reduced Intensity AlloTransplant For Osteopetrosis
NCT00968864	PHASE2	TERMINATED	T-cell Depleted Alternative Donor Transplantation
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT02666768	PHASE2	COMPLETED	ACTIMMUNE in Intermediate Osteopetrosis
NCT00145886	PHASE1	TERMINATED	rhPTH Therapy for Low Turnover Bone Fragility
NCT00775931	PHASE2/PHASE3	COMPLETED	Allogeneic Transplantation For Severe Osteopetrosis
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT01087398	PHASE2/PHASE3	UNKNOWN	Hematopoietic Stem Cell Transplantation for Malignant Infantile Osteopetrosis
NCT00730314	PHASE1/PHASE2	COMPLETED	Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
NCT02065869	PHASE1/PHASE2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
NCT03301168	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
NCT00043329	Not specified	COMPLETED	Post Marketing Surveillance Study of Actimmune in Patients With Severe, Malignant Osteopetrosis
NCT00145587	Not specified	TERMINATED	Stem Cell Transplantation for Children Affected With Osteopetrosis
NCT01199094	Not specified	COMPLETED	Clinical Assessment of Patients With High Bone Mass Due to Mutation in Lrp5
NCT01200017	Not specified	NO_LONGER_AVAILABLE	Expanded Access Protocol (EAP) Using the CliniMACS® Device for Pediatric Haplocompatible Donor Stem Cell Transplant
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT06521580	Not specified	COMPLETED	Outcomes of Patients With Osteopetrosis Weight-bearing Bone Fractures