CA9

Summary

CA9 (carbonic anhydrase 9, HGNC:1383) is a protein-coding gene on chromosome 9p13.3, encoding Carbonic anhydrase 9 (Q16790). Catalyzes the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions).

Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. CA IX is a transmembrane protein and is one of only two tumor-associated carbonic anhydrase isoenzymes known. It is expressed in all clear-cell renal cell carcinoma, but is not detected in normal kidney or most other normal tissues. It may be involved in cell proliferation and transformation. This gene was mapped to 17q21.2 by fluorescence in situ hybridization, however, radiation hybrid mapping localized it to 9p13-p12.

Source: NCBI Gene 768 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 89 total
• Druggable target: yes — 68 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001216

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1383
Approved symbol	CA9
Name	carbonic anhydrase 9
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MN, CAIX
Ensembl gene	ENSG00000107159
Ensembl biotype	protein_coding
OMIM	603179
Entrez	768

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000378357, ENST00000485665, ENST00000493245, ENST00000903366, ENST00000903367

RefSeq mRNA: 1 — MANE Select: NM_001216 NM_001216

CCDS: CCDS6585

Canonical transcript exons

ENST00000378357 — 11 exons

Exon	Start	End
ENSE00000928221	35676064	35676206
ENSE00001048272	35676297	35676389
ENSE00001091961	35675538	35675567
ENSE00001091964	35675761	35675931
ENSE00001477244	35673928	35674362
ENSE00003475680	35679185	35679342
ENSE00003547069	35679854	35679998
ENSE00003549260	35680113	35680139
ENSE00003569187	35680753	35680834
ENSE00003601142	35680965	35681159
ENSE00003637783	35677790	35677856

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 94.44.

FANTOM5 (CAGE): breadth broad, TPM avg 6.7613 / max 327.0436, expressed in 402 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96612	6.0741	381
96613	0.3671	104
96611	0.3201	119

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of stomach	UBERON:0001161	94.44	gold quality
gall bladder	UBERON:0002110	93.06	gold quality
fundus of stomach	UBERON:0001160	92.54	gold quality
stomach	UBERON:0000945	92.39	gold quality
cardia of stomach	UBERON:0001162	90.29	gold quality
cerebellar hemisphere	UBERON:0002245	90.19	gold quality
cerebellar cortex	UBERON:0002129	89.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.79	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.32	gold quality
cerebellum	UBERON:0002037	87.94	gold quality
right testis	UBERON:0004534	87.83	gold quality
pylorus	UBERON:0001166	87.77	gold quality
left testis	UBERON:0004533	87.68	gold quality
testis	UBERON:0000473	84.53	gold quality
germinal epithelium of ovary	UBERON:0001304	82.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.56	gold quality
lower esophagus	UBERON:0013473	81.51	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.23	gold quality
duodenum	UBERON:0002114	80.32	gold quality
paraflocculus	UBERON:0005351	79.95	gold quality
frontal pole	UBERON:0002795	79.82	gold quality
ascending aorta	UBERON:0001496	79.73	gold quality
thoracic aorta	UBERON:0001515	79.44	gold quality
middle frontal gyrus	UBERON:0002702	78.90	gold quality
aorta	UBERON:0000947	78.64	gold quality
muscle layer of sigmoid colon	UBERON:0035805	78.26	gold quality
descending thoracic aorta	UBERON:0002345	78.25	gold quality
skin of abdomen	UBERON:0001416	78.14	gold quality
popliteal artery	UBERON:0002250	78.14	gold quality
tibial artery	UBERON:0007610	78.13	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	714.29
E-ANND-3	yes	6.23
E-MTAB-7249	no	212.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, ARNT, ATF4, CUX1, EP300, EPAS1, ETS1, FOS, HDAC4, HIF1A, PAX1, SP1, SP3, TFAP2A, TP53, UTF1, VHL

miRNA regulators (miRDB)

5 targeting CA9, 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-548AU-3P	99.70	68.22	1373
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-4468	98.01	66.85	1187

Literature-anchored findings (GeneRIF, showing 40)

• Human CA IX was very strongly inhibited by three classic sulfonamides and cyanate (PMID:11676494)
• CA9 might be a marker of clinically important hypoxia. (PMID:11705854)
• The methylation status of the G250 gene correlates with G250 expression in vitro but not in vivo. (PMID:12137853)
• Lowered oxygen tension induces expression of the hypoxia marker MN/carbonic anhydrase IX in the absence of hypoxia-inducible factor 1 alpha stabilization: a role for phosphatidylinositol 3’-kinase. (PMID:12154057)
• mCA IX is a marker of tumor cell hypoxia, and absence of CA IX staining close to microvessels suggests that these vessels are functionally active; pCA IX expression is representative of an aggressive phenotype (PMID:12560438)
• This enzyme is an independent predictor for survival in advanced renal clear cell carcinoma. (PMID:12576453)
• Expression of the hypoxia marker carbonic anhydrase IX is critically dependent on SP1 activity. (PMID:12615703)
• The variations observed in the CA IX levels support the concept that gastric adenomas and carcinomas are distinct entities and do not represent progressive steps of a single pathway. (PMID:12854129)
• CA9 is detectable in breast tumor and associated with resistance to both adjuvant chemotherapy and endocrine therapy (PMID:12865916)
• No correlation between CA IX expression and tumor pO(2) levels or patient outcome in locally advanced carcinomas of the cervix. (PMID:14654550)
• significantly higher rate of strong CA IX expression in non-invasive cancers influences survival data (PMID:15069539)
• HIF-1alpha and Sp1, in combination with CBP/p300, are crucial elements for G250MN expression in ccRCC, and CAIXG250 can be regarded as a unique HIF-1alpha target gene in ccRCC. (PMID:15184875)
• upon activation by DNA damage, wt p53 mediates an accelerated degradation of HIF-1alpha protein, resulting in reduced activation of CA9 transcription and, correspondingly, decreased levels of CA9 protein (PMID:15199132)
• CAIX has a role in progression of high-grade soft tissue sarcoma (PMID:15240538)
• tumors with higher redox state exhibited an algebraically lower CA IX expression (PMID:15500003)
• Cell hypoxia activates the capacity of tumor-associated CA9 to acidify extracellular pH. (PMID:15556624)
• Increased carbonic anhydrase IX is associated with non-small cell lung cancer (PMID:15585626)
• CA9 is expressed in head and neck squamous cell carcinomas, suggesting the presence of a population of tumor cells under intermediate hypoxic conditions which still has proliferative capacity (PMID:15671533)
• Expressed in a high percentage of human cancers derived from tissues which are normally CA IX-negative. (PMID:15809767)
• MAPK cascade is involved in the regulation of CA9 gene expression under both hypoxia and high cell density. (PMID:15833446)
• Isothiocyanato sulfonamide thioureas inhibit this enzyme. (PMID:15837325)
• CA IX and GLUT 1 as well as VEGF and IL 6 have roles in response of in head and neck squamous cell carcinoma to radiotherapy +/- chemotherapy (PMID:15847702)
• The interplay between the functional von Hippel-Lindau tumor suppressor and CA IX/CA XII in colorectal tumors seems rather complex and is not evident merely at the expression levels. (PMID:15849821)
• potential value of CA9 as a molecular marker for the assessment of regional lymph node status in vulvar cancer patients (PMID:15856466)
• HIF-1alpha and CA IX, but not VEGF or MMP-9, may have a role in progression of surgically resected non-small cell lung cancer (PMID:15935515)
• Coexpression of HIF-1alpha and CAIX in the epithelium in phyllodes tumors points to epithelial hypoxia, most probably caused by relatively distant blood vessels. (PMID:16168127)
• Data indicate expression of Carbonic anhydrase IX does not correlate with the oxygenation status. (PMID:16243791)
• Collectively these findings establish the importance of intracellular ascorbate levels for the regulation of expression of CA IX and NDRG1/Cap43. (PMID:16288478)
• The strong correlation between CA9 expression and metastasis suggests that CA9 expression might be an important indicator for identifying patients who require more aggressive systemic therapy. (PMID:16416108)
• High levels of carbonic anhydrase IX is associated with astrocytoma (PMID:16428489)
• High carbonic anhydrase IX expression is associated with non-small cell lung cancers (PMID:16533775)
• Immunohistochemical carbonic anhydrase IX staining in human malignant glioma specimens can result from low oxygen concentrations or constitutive, oncogene-related, overexpression both of which may be prognostically relevant. (PMID:16944313)
• CAIX expression in breast cancer patients shows a negative predictive role of treatment efficacy in estrogen receptor-positive patients. (PMID:16954440)
• Acidosis increases the CA IX expression via a hypoxia-independent mechanism that operates through modulation of the basic CA9 transcriptional machinery. (PMID:16964400)
• carbonic anhydrase 9 expression is associated with anaplastic phenotypes in meningiomas (PMID:17200340)
• Overexpression of carbonic anhydrase IX is associated with breast carcinomas (PMID:17245699)
• evidence CAIX expression in astrocytic glioma is related to HIF-1alpha & VEGF & associated with extent of necrosis, grade, proliferative potential & morphometric characteristics of microvessels; may be used as prognostic indicator in diffuse astrocytoma (PMID:17367605)
• study confirms that the expression level of CA9 gene in conventional renal cell carcinoma is related to metastasis (PMID:17390110)
• The role of protein expression of hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, carbonic anhydrase 9 (CA9) and glucose transporter 1 (GLUT1) in patients with colorectal adenocarcinomas. (PMID:17452775)
• MN/CA9 gene expression was detected in 53/59 (89.8%) pleural effusions from cancer patients (15/16 breast cancers, 10/11 lung cancers, 4/4 ovary cancers, 2/3 colon-rectal cancers, 5/6 cancers of unknown site, 7/8 mesothelioma & 10/11 other cancers) (PMID:17536770)

Cross-species orthologs

18 orthologs

Organism	Symbol	Gene ID
danio_rerio	cahz	ENSDARG00000011166
danio_rerio	ca2	ENSDARG00000014488
mus_musculus	Car9	ENSMUSG00000028463
rattus_norvegicus	Car9	ENSRNOG00000017073
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), 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 9 — Q16790 (reviewed: Q16790)

Alternative names: Carbonate dehydratase IX, Carbonic anhydrase IX, Membrane antigen MN, P54/58N, Renal cell carcinoma-associated antigen G250, pMW1

All UniProt accessions (2): Q16790, A0A0S2Z3D0

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions).

Subunit / interactions. Forms oligomers linked by disulfide bonds.

Subcellular location. Nucleus. Nucleolus. Cell membrane. Cell projection. Microvillus membrane.

Tissue specificity. Expressed primarily in carcinoma cells lines. Expression is restricted to very few normal tissues and the most abundant expression is found in the epithelial cells of gastric mucosa.

Post-translational modifications. Asn-346 bears high-mannose type glycan structures.

Activity regulation. Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide (AZA) and Foscarnet (phosphonoformate trisodium salt).

Induction. By hypoxia.

Similarity. Belongs to the alpha-carbonic anhydrase family.

RefSeq proteins (1): NP_001207* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001148	CA_dom	Domain
IPR018338	Carbonic_anhydrase_a-class_CS	Conserved_site
IPR023561	Carbonic_anhydrase_a-class	Family
IPR036398	CA_dom_sf	Homologous_superfamily

Pfam: PF00194

Enzyme classification (BRENDA):

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

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
CO2	0.012–4700	194
4-NITROPHENYL ACETATE	0.0024–30.53	16
H2CO3	0.434–112.7	16
HCO3-	9.3–37	4
P-NITROPHENYL ACETATE	3.86–6.8	4
4-NITROPHENYL PHOSPHATE	0.935–2.195	2
COS	1.86	1
HISTAMINE	7.9	1
CS2	—	0

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (51 total): strand 16, helix 8, binding site 4, compositionally biased region 3, turn 3, region of interest 3, glycosylation site 2, topological domain 2, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, active site 1, modified residue 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6RQQ	X-RAY DIFFRACTION	1.28
6RQU	X-RAY DIFFRACTION	1.39
6RQW	X-RAY DIFFRACTION	1.49
6Y74	X-RAY DIFFRACTION	1.53
5DVX	X-RAY DIFFRACTION	1.6
6G9U	X-RAY DIFFRACTION	1.75
6RQN	X-RAY DIFFRACTION	1.78
5FL4	X-RAY DIFFRACTION	1.82
6FE2	X-RAY DIFFRACTION	1.87
6FE0	X-RAY DIFFRACTION	1.91
5FL6	X-RAY DIFFRACTION	1.95
6FE1	X-RAY DIFFRACTION	1.95
6QN2	X-RAY DIFFRACTION	1.95
9R8Y	X-RAY DIFFRACTION	1.95
9RBM	X-RAY DIFFRACTION	1.95
6QN5	X-RAY DIFFRACTION	1.96
6QUT	X-RAY DIFFRACTION	1.96
7POM	X-RAY DIFFRACTION	1.98
9R8X	X-RAY DIFFRACTION	2
2HKF	X-RAY DIFFRACTION	2.01
5FL5	X-RAY DIFFRACTION	2.05
9RBL	X-RAY DIFFRACTION	2.05
8Q18	X-RAY DIFFRACTION	2.13
6TL6	X-RAY DIFFRACTION	2.15
3IAI	X-RAY DIFFRACTION	2.2
9FLF	X-RAY DIFFRACTION	2.2
6TL5	X-RAY DIFFRACTION	2.21
6QN6	X-RAY DIFFRACTION	2.25
8CO0	X-RAY DIFFRACTION	2.3
8Q1A	X-RAY DIFFRACTION	2.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16790-F1	77.13	0.58

Antibody-complex structures (SAbDab): 1 — 2HKF

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): 200 (proton donor/acceptor)

Ligand- & substrate-binding residues (4): 226; 228; 251; 332–333

Post-translational modifications (1): 449

Disulfide bonds (2): 156–336, 174

Glycosylation sites (2): 115, 346

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1234158	Regulation of gene expression by Hypoxia-inducible Factor
R-HSA-1475029	Reversible hydration of carbon dioxide
R-HSA-1234174	Cellular response to hypoxia
R-HSA-1430728	Metabolism
R-HSA-2262752	Cellular responses to stress
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 153 (showing top): AP1_01, HARRIS_HYPOXIA, GOMF_CARBONATE_DEHYDRATASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, NFKB_C, SEMENZA_HIF1_TARGETS, GOBP_RESPONSE_TO_TESTOSTERONE, GOBP_RESPONSE_TO_KETONE, GOBP_RESPONSE_TO_OXYGEN_LEVELS, chr9p13, BACH2_01, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (5): response to hypoxia (GO:0001666), morphogenesis of an epithelium (GO:0002009), response to xenobiotic stimulus (GO:0009410), response to testosterone (GO:0033574), secretion (GO:0046903)

GO Molecular Function (6): carbonate dehydratase activity (GO:0004089), zinc ion binding (GO:0008270), molecular function activator activity (GO:0140677), protein binding (GO:0005515), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleolus (GO:0005730), plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), microvillus membrane (GO:0031528), nucleus (GO:0005634), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cellular response to hypoxia	1
Metabolism	1
Cellular responses to stress	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
response to stress	1
response to decreased oxygen levels	1
tissue morphogenesis	1
epithelium development	1
response to chemical	1
response to lipid	1
response to ketone	1
transport	1
hydro-lyase activity	1
transition metal ion binding	1
molecular function regulator activity	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
microvillus	1
cell projection membrane	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2648 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CA9	SLC16A4	O15374	886
CA9	SLC16A3	O15427	878
CA9	SLC2A1	P11166	832
CA9	EPAS1	Q99814	816
CA9	HIF1A	Q16665	815
CA9	CYP24A1	Q07973	766
CA9	VHL	P40337	761
CA9	DNAJB7	Q7Z6W7	761
CA9	EGLN3	Q9H6Z9	732
CA9	TECR	Q9NZ01	697
CA9	SLC49A4	Q96SL1	694
CA9	EGLN1	Q9GZT9	668
CA9	AMACR	Q9UHK6	667
CA9	HIF1AN	Q9NWT6	660
CA9	BSG	P35613	653

IntAct

18 interactions, top by confidence:

A	B	Type	Score
CA9	GLRX3	psi-mi:“MI:0915”(physical association)	0.740
GLRX3	CA9	psi-mi:“MI:0915”(physical association)	0.740
CSRP1	CA9	psi-mi:“MI:0915”(physical association)	0.560
CA9	CA9	psi-mi:“MI:0407”(direct interaction)	0.440
SOX2	HAX1	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
POLD3	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
CA9	GLRX3	psi-mi:“MI:0915”(physical association)	0.000
CSRP1	CA9	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (229): CA9 (Protein-peptide), CAND1 (Affinity Capture-Western), CA9 (Co-localization), CA9 (Co-localization), GLRX3 (Two-hybrid), CA9 (Co-localization), CA9 (Co-localization), CTNNB1 (Affinity Capture-Western), CDH1 (Affinity Capture-Western), CTNNA1 (Affinity Capture-Western), NAGK (Positive Genetic), CNTFR (Positive Genetic), NPR2 (Positive Genetic), CA9 (Co-localization), TMPO (Proximity Label-MS)

ESM2 similar proteins: A6QQ92, A8MV23, O00292, O43508, O54907, O75610, P01017, P01019, P05155, P08697, P20757, P23035, P28800, P36955, P41155, P49920, P50448, P62503, P70225, P97290, P97298, Q09055, Q13477, Q14626, Q16790, Q5RF19, Q61247, Q63148, Q64280, Q64385, Q6IN84, Q6P734, Q6UXC1, Q6UXR4, Q76LW6, Q7TPA5, Q86U17, Q86UR1, Q8CIE0, Q8N907

Diamond homologs: A0ZSF2, A0ZSF3, A0ZSF4, A0ZSF5, A0ZSF6, A0ZSF7, B3A0P2, B3A0Q6, B8V7P3, F4HUC4, O43570, P08060, P18761, P22748, P23280, P23471, P23589, P35218, P43165, P48284, P83299, P84537, Q10462, Q16790, Q27504, Q27908, Q62656, Q84UV8, Q865C0, Q8CI85, Q8UWA5, Q8VHB5, Q92051, Q9ERQ8, Q9FM99, Q9MZ30, Q9NL38, Q9QZA0, Q9Y2D0, P07630

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKACA	up-regulates	CA9	phosphorylation
ARNT	“up-regulates quantity by expression”	CA9	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1251 predictions. Top by Δscore:

Variant	Effect	Δscore
9:35674358:AGAAG:A	donor_gain	1.0000
9:35674359:GAAG:G	donor_gain	1.0000
9:35674359:GAAGG:G	donor_gain	1.0000
9:35674360:AAG:A	donor_gain	1.0000
9:35674360:AAGG:A	donor_loss	1.0000
9:35674361:AG:A	donor_gain	1.0000
9:35674361:AGGT:A	donor_loss	1.0000
9:35674362:GG:G	donor_gain	1.0000
9:35674363:G:GG	donor_gain	1.0000
9:35674363:GTAA:G	donor_loss	1.0000
9:35676387:G:GT	donor_gain	1.0000
9:35677853:G:GT	donor_gain	1.0000
9:35677854:A:T	donor_gain	1.0000
9:35680111:A:AG	acceptor_gain	1.0000
9:35680112:G:GG	acceptor_gain	1.0000
9:35675757:CCA:C	acceptor_loss	0.9900
9:35675758:CA:C	acceptor_loss	0.9900
9:35675759:A:AG	acceptor_gain	0.9900
9:35675760:G:GC	acceptor_loss	0.9900
9:35675760:G:GG	acceptor_gain	0.9900
9:35675760:GGC:G	acceptor_gain	0.9900
9:35675929:GTG:G	donor_gain	0.9900
9:35675937:G:GT	donor_gain	0.9900
9:35676062:A:AG	acceptor_gain	0.9900
9:35676063:G:GG	acceptor_gain	0.9900
9:35676291:TTTCA:T	acceptor_loss	0.9900
9:35676292:TTCA:T	acceptor_loss	0.9900
9:35676293:TCA:T	acceptor_loss	0.9900
9:35676294:CA:C	acceptor_loss	0.9900
9:35676295:AG:A	acceptor_loss	0.9900

AlphaMissense

2922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:35679262:G:T	G329W	0.985
9:35676146:G:C	W229C	0.981
9:35676146:G:T	W229C	0.981
9:35676141:C:G	H228D	0.980
9:35679911:T:C	F375L	0.979
9:35679913:C:A	F375L	0.979
9:35679913:C:G	F375L	0.979
9:35676172:A:T	E238V	0.977
9:35679256:T:C	Y327H	0.977
9:35679910:C:A	N374K	0.977
9:35679910:C:G	N374K	0.977
9:35679257:A:G	Y327C	0.976
9:35679303:G:C	W342C	0.976
9:35679303:G:T	W342C	0.976
9:35679283:T:A	C336S	0.975
9:35679284:G:C	C336S	0.975
9:35680797:A:C	S428R	0.974
9:35680799:C:A	S428R	0.974
9:35680799:C:G	S428R	0.974
9:35676173:G:C	E238D	0.973
9:35676173:G:T	E238D	0.973
9:35676176:C:A	H239Q	0.973
9:35676176:C:G	H239Q	0.973
9:35679301:T:A	W342R	0.973
9:35679301:T:C	W342R	0.973
9:35679956:T:C	F390L	0.973
9:35679958:C:A	F390L	0.973
9:35679958:C:G	F390L	0.973
9:35675918:C:A	N197K	0.972
9:35675918:C:G	N197K	0.972

dbSNP variants (sampled 300 via entrez): RS1000059538 (9:35679586 G>C), RS1000405272 (9:35673189 GA>G), RS1000492441 (9:35675416 C>G,T), RS1000964737 (9:35673534 A>T), RS1001097048 (9:35673860 C>T), RS1001539503 (9:35678744 A>G,T), RS1001574212 (9:35672854 C>T), RS1002505225 (9:35672208 C>T), RS1002510278 (9:35674414 C>T), RS1002542657 (9:35677268 C>A), RS1002949113 (9:35677531 G>A,C), RS1003544027 (9:35676107 C>A,G,T), RS1004316137 (9:35678720 C>A,G,T), RS1004684680 (9:35674983 A>C), RS1004709945 (9:35681184 C>T)

Disease associations

OMIM: gene MIM:603179 | disease phenotypes: MIM:613659

GenCC curated gene-disease

Mondo (1): gastric cancer (MONDO:0001056)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2095180 (PROTEIN FAMILY), CHEMBL2096906 (SELECTIVITY GROUP), CHEMBL3594 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

68 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,661,057 (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
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1200471	PYRITHIONE ZINC	4	24,834
CHEMBL1286	LEVETIRACETAM	4	13,997
CHEMBL1336	SORAFENIB	4	86,060
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	58,543
CHEMBL325041	BORTEZOMIB	4
CHEMBL328560	SULTHIAME	4
CHEMBL35	FUROSEMIDE	4
CHEMBL406	INDAPAMIDE	4
CHEMBL419	MAFENIDE	4
CHEMBL424	SALICYLIC ACID	4
CHEMBL4303669	ZOLEDRONIC ACID	4
CHEMBL467	HYDROXYUREA	4
CHEMBL477772	PAZOPANIB	4
CHEMBL537	HYDROQUINONE	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	7.51	pKi
SLC-0111	Inhibition	7.35	pKi
compound 5a [PMID: 31287314]	Inhibition	6.38	pKi
gamma-valerolactone	Inhibition	6.04	pKi
compound 5b [PMID: 31287314]	Inhibition	5.0	pKi

Binding affinities (BindingDB)

281 measured of 310 human assays (346 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
4-(3-(2-cyanophenyl)ureido)benzenesulfonamide	KI	0.3 nM
4-(3-(3-nitrophenyl)ureido)benzenesulfonamide	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
2-N-(4-amino-3-chloro-5-fluorobenzene)-1,3,4-thiadiazole-2,5-disulfonamide	KI	1.4 nM
N-[2-(diethylamino)ethyl]-4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]benzamide	KI	1.4 nM
2-N-(4-amino-3-fluoro-5-iodobenzene)-1,3,4-thiadiazole-2,5-disulfonamide	KI	1.7 nM
5-(4-Amino-3-bromobenzenesulfonamido)-1,3,4-thiadiazole-2-sulfonamide	KI	1.9 nM
5-(4-Amino-3,5-diiodobenzenesulfonamido)-1,3,4-thiadiazole-2-sulfonamide	KI	2.1 nM
2-N-(4-amino-3-chlorobenzene)-1,3,4-thiadiazole-2,5-disulfonamide	KI	2.5 nM
(4S)-4-(ethylamino)-2-(3-methoxypropyl)-1,1-dioxo-2H,3H,4H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide	KI	3 nM
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
aliphatic sulfamate, 1	KI	3.7 nM
2,4,6-trimethyl-1-{4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}-1-pyridin-1-ylium perchlorate	KI	4 nM
2,4-dimethyl-6-(propan-2-yl)-1-{4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}-1-pyridin-1-ylium perchlorate	KI	4 nM
1-N-[5-Sulfamoyl-1,3,4-thiadiazol-2-yl-(aminosulfonyl-4-phenyl)]-2,6-diethyl-4-phenylpyridinium perchlorate	KI	4 nM
2-methyl-4,6-diphenyl-1-{4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}-1-pyridin-1-ylium perchlorate	KI	4 nM
5-(4-Acetamido-3-chlorobenzenesulfonamido)-1,3,4-thiadiazole-2-sulfonamide	KI	5 nM
5-(4-Acetamido-3-bromobenzenesulfonamido)-1,3,4-thiadiazole-2-sulfonamide	KI	5 nM
4-sulfamoyl-N-[2-(4-sulfamoylphenyl)ethyl]benzamide	KI	5 nM
4-phenyl-2,6-bis(propan-2-yl)-1-{4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}-1-pyridin-1-ylium perchlorate	KI	5 nM
2-ethyl-4,6-diphenyl-1-{4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}-1-pyridin-1-ylium perchlorate	KI	5 nM
1-N-[5-Sulfamoyl-1,3,4-thiadiazol-2-yl-(aminosulfonyl-4-phenyl)]-2,4,6-triphenylpyridinium perchlorate	KI	5 nM
2,6-diphenyl-1-{4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}-1-pyridin-1-ylium perchlorate	KI	5 nM
4-ureidophenyl sulfamate ring derivative 3o	KI	5 nM
4-(3-(4-acetylphenyl)ureido)benzenesulfonamide	KI	5.4 nM
aminobenzolamide deriv. 40	KI	5.7 nM
2,4-diphenyl-6-(propan-2-yl)-1-{4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}-1-pyridin-1-ylium perchlorate	KI	6 nM
4-methyl-2,6-diphenyl-1-{4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}-1-pyridin-1-ylium perchlorate	KI	6 nM
4-ureidophenyl sulfamate ring derivative 3j	KI	6 nM
4-ureidophenyl sulfamate ring derivative 3m	KI	6 nM
4-ureidophenyl sulfamate ring derivative 3az	KI	6 nM
4-(4-{[(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)oxy]methyl}-1H-1,2,3-triazol-1-yl)benzenesulfonamide	KI	6.9 nM
4-methyl-2,6-bis(propan-2-yl)-1-{4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}-1-pyridin-1-ylium perchlorate	KI	7 nM
4-[4-({[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}methyl)-1H-1,2,3-triazol-1-yl]benzene-1-sulfonamide	KI	7 nM
Benzolamide, BZM	KI	7 nM
4-ureidophenyl sulfamate ring derivative 3p	KI	7 nM
4-ureidophenyl sulfamate ring derivative 3as	KI	7 nM
4-ureidophenyl sulfamate ring derivative 3aw	KI	7 nM
4-[4-({[(2R,3R,4R,5S,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-{[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}oxan-2-yl]oxy}methyl)-1H-1,2,3-triazol-1-yl]benzene-1-sulfonamide	KI	7.3 nM
4-({[4-(Aminosulfonyl)benzoyl]oxy}methyl-1-(beta-D-arabinopyranosyl)-1H-1,2,3-triazole	KI	7.7 nM
2,4-diphenyl-6-propyl-1-{4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}-1-pyridin-1-ylium perchlorate	KI	8 nM
1-N-[5-Sulfamoyl-1,3,4-thiadiazol-2-yl-(aminosulfonyl-4-phenyl)]-2-n-butyl-4,6-diphenylpyridinium perchlorate	KI	8 nM
4-ureidophenyl sulfamate ring derivative 3q	KI	8 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	Kd	0.01	nM	CHEMBL4543024
11.00	Kd	0.01	nM	CHEMBL4456851
11.00	Kd	0.01	nM	CHEMBL4553519
11.00	Kd	0.01	nM	CHEMBL4551069
11.00	Kd	0.01	nM	CHEMBL4565560
11.00	Kd	0.01	nM	CHEMBL4558287
11.00	Kd	0.01	nM	CHEMBL4583164
11.00	Kd	0.01	nM	CHEMBL4573963
10.96	Kd	0.011	nM	CHEMBL4176828
10.96	Kd	0.011	nM	CHEMBL4174214
10.96	Kd	0.011	nM	CHEMBL4474251
10.92	Kd	0.012	nM	CHEMBL4516072
10.92	Kd	0.012	nM	CHEMBL4462447
10.72	Kd	0.019	nM	CHEMBL4160627
10.70	Kd	0.02	nM	CHEMBL4205449
10.70	Kd	0.02	nM	CHEMBL4465972
10.70	Kd	0.02	nM	CHEMBL4562296
10.70	Kd	0.02	nM	CHEMBL4468310
10.70	Kd	0.02	nM	CHEMBL4463844
10.70	Kd	0.02	nM	CHEMBL4579465
10.70	Kd	0.02	nM	CHEMBL4514121
10.70	Kd	0.02	nM	CHEMBL4517317
10.70	Kd	0.02	nM	CHEMBL4582964
10.62	Kd	0.024	nM	CHEMBL4457904
10.60	Kd	0.025	nM	CHEMBL4177268
10.57	Kd	0.027	nM	CHEMBL4441730
10.52	Kd	0.03	nM	CHEMBL4567746
10.52	Kd	0.03	nM	CHEMBL4578934
10.52	Kd	0.03	nM	CHEMBL4456084
10.52	Kd	0.03	nM	CHEMBL4565224
10.52	Kd	0.03	nM	CHEMBL4592616
10.52	Kd	0.03	nM	CHEMBL4469236
10.52	Kd	0.03	nM	CHEMBL4584546
10.52	Kd	0.03	nM	CHEMBL4439634
10.49	Kd	0.032	nM	CHEMBL4573916
10.49	Kd	0.032	nM	CHEMBL4539340
10.46	Kd	0.035	nM	CHEMBL4473602
10.46	Kd	0.035	nM	CHEMBL4463683
10.46	Kd	0.035	nM	CHEMBL4461481
10.46	Kd	0.035	nM	CHEMBL4464359
10.44	Kd	0.036	nM	CHEMBL4555622
10.40	Kd	0.04	nM	CHEMBL4593681
10.35	Kd	0.045	nM	CHEMBL4517728
10.30	Kd	0.05	nM	CHEMBL3359181
10.30	Kd	0.05	nM	CHEMBL4218335
10.30	Kd	0.05	nM	CHEMBL4443095
10.30	Kd	0.05	nM	CHEMBL4459385
10.30	Kd	0.05	nM	CHEMBL4566236
10.29	Kd	0.051	nM	CHEMBL4516858
10.23	Kd	0.059	nM	CHEMBL4446249

PubChem BioAssay actives

5128 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
3-[(4-chloro-2-phenylsulfanyl-5-sulfamoylbenzoyl)amino]propyl acetate	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-N-(2-hydroxyethyl)-2-phenylsulfanyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-(cyclohexylamino)-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1361389: Binding affinity to recombinant human carbonic anhydrase 9 (38 to 414 residues) expressed in 293-F cells assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
2-benzylsulfanyl-N-butyl-4-chloro-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-butyl-2-(cyclohexylamino)-5-sulfamoylbenzamide	1361389: Binding affinity to recombinant human carbonic anhydrase 9 (38 to 414 residues) expressed in 293-F cells assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-(2-hydroxyethyl)-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzenesulfonyl)-4-chloro-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-butyl-2-cyclohexylsulfanyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzenesulfonyl)-4-chloro-N-(2-methoxyethyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzylamino)-N-butyl-4-chloro-5-sulfamoylbenzamide	1361389: Binding affinity to recombinant human carbonic anhydrase 9 (38 to 414 residues) expressed in 293-F cells 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	1361389: Binding affinity to recombinant human carbonic anhydrase 9 (38 to 414 residues) expressed in 293-F cells assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
2-benzylsulfanyl-4-bromo-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-butyl-4-chloro-2-(cyclooctylamino)-5-sulfamoylbenzamide	1361389: Binding affinity to recombinant human carbonic anhydrase 9 (38 to 414 residues) expressed in 293-F cells 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	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-2-cyclohexylsulfanyl-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-benzylsulfanyl-4-bromo-N-butyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-butyl-2-(2-hydroxyethylsulfanyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-benzyl-2-(benzylamino)-4-chloro-5-sulfamoylbenzamide	1361389: Binding affinity to recombinant human carbonic anhydrase 9 (38 to 414 residues) expressed in 293-F cells 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	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-butyl-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-(2-hydroxyethyl)-2-phenylsulfanyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-butyl-4-chloro-2-phenylsulfanyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-butyl-4-chloro-2-cyclohexylsulfonyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-N-(2-methoxyethyl)-2-phenylsulfanyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzenesulfonyl)-N-benzyl-4-chloro-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-cyclohexylsulfanyl-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-cyclohexylsulfonyl-N-(2-methoxyethyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-butyl-4-chloro-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzylamino)-4-chloro-N-(2-methoxyethyl)-5-sulfamoylbenzamide	1361389: Binding affinity to recombinant human carbonic anhydrase 9 (38 to 414 residues) expressed in 293-F cells assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-2-cyclohexylsulfonyl-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-cyclohexylsulfanyl-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-benzyl-4-chloro-2-cyclohexylsulfonyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-benzylsulfanyl-4-chloro-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzylamino)-4-chloro-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1361389: Binding affinity to recombinant human carbonic anhydrase 9 (38 to 414 residues) expressed in 293-F cells assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzenesulfonyl)-4-bromo-N-butyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-benzyl-4-chloro-2-phenylsulfanyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-cyclohexylsulfanyl-N-(2-methoxyethyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
methyl 4-[(4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzoyl)amino]butanoate	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-[(4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzoyl)amino]butanoic acid	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-N-cyclohexyl-2-cyclohexylsulfonyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-benzyl-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-butyl-2-cyclohexylsulfonyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-butyl-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-N-cyclohexyl-2-cyclohexylsulfanyl-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
methyl 4-[(4-chloro-2-cyclohexylsulfonyl-5-sulfamoylbenzoyl)amino]butanoate	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-cyclohexylsulfonyl-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzenesulfonyl)-N-butyl-4-chloro-5-sulfamoylbenzamide	1520087: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-(cyclohexylamino)-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1361389: Binding affinity to recombinant human carbonic anhydrase 9 (38 to 414 residues) expressed in 293-F cells assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
N-butyl-4-chloro-2-(cyclohexylamino)-5-sulfamoylbenzamide	1361389: Binding affinity to recombinant human carbonic anhydrase 9 (38 to 414 residues) expressed in 293-F cells assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	<0.0001	uM
3-(cyclooctylamino)-2,5,6-trifluoro-4-propylsulfonylbenzenesulfonamide	1295826: Binding affinity to human recombinant CA9 catalytic domain by fluorescence-based thermal shift assay	kd	<0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Oxygen	affects binding, affects cotreatment, decreases reaction, increases expression, increases reaction	23
cobaltous chloride	decreases reaction, increases expression, increases reaction	10
Benzo(a)pyrene	decreases methylation, affects cotreatment, decreases expression, increases abundance, affects methylation (+2 more)	5
sodium arsenite	affects expression, decreases expression, increases expression	3
(+)-JQ1 compound	affects binding, decreases reaction, increases reaction, increases expression, decreases expression	3
Air Pollutants	increases abundance, increases expression, affects cotreatment, decreases expression	3
Estradiol	affects cotreatment, decreases expression	3
Cadmium Chloride	decreases expression, increases expression	3
propionaldehyde	decreases expression	2
bisphenol A	affects expression, increases expression	2
butyraldehyde	decreases expression	2
nickel chloride	increases reaction, increases expression	2
nickel sulfate	decreases expression, decreases reaction, increases expression	2
pentanal	decreases expression	2
Acetazolamide	affects binding, decreases activity	2
Betulinic Acid	decreases activity, decreases reaction, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Vanadates	decreases activity, increases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
1-cyclopropyl-4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl)pyridin-2-yl)piperazine	decreases reaction, increases expression, decreases expression, increases reaction	1
gamabufotalin	decreases expression	1
SLC-0111	affects binding, decreases activity	1
CAY10591	decreases reaction, increases expression	1
sotorasib	affects cotreatment, decreases expression	1
triptolide	decreases reaction, increases expression	1
betulin	decreases reaction, increases expression	1
tungsten carbide	affects binding, increases expression	1
methyleugenol	decreases expression	1

ChEMBL screening assays

791 unique, capped per target: 785 binding, 5 admet, 1 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
CHEMBL4044595	ADMET	Inhibition of human CA9	1,3-Oxazole-based selective picomolar inhibitors of cytosolic human carbonic anhydrase II alleviate ocular hypertension in rabbits: Potency is supported by X-ray crystallography of two leads. — Bioorg Med Chem
CHEMBL834888	Functional	Inhibition constant against human recombinant carbonic anhydrase IX catalytic domain	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

6 cell lines: 5 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_5M65	RenCa/CA-IX	Cancer cell line	Male
CVCL_B8CA	Abcam HCT 116 CA9 KO	Cancer cell line	Male
CVCL_B8T7	Abcam MCF-7 CA9 KO	Cancer cell line	Female
CVCL_B9EG	Abcam A-549 CA9 KO	Cancer cell line	Male
CVCL_D7L6	Ubigene A-549 CA9 KO	Cancer cell line	Male
CVCL_E6P4	Genomeditech CHO-K1 H_CA9	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT01962376	PHASE4	UNKNOWN	Preoperative Chemotherapy With Bevacizumab For Potentially Resectable Gastric Cancer With Liver Metastasis
NCT02047994	PHASE4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT02235246	PHASE4	COMPLETED	The Effect of Perioperative Intravenous Magnesium on Pain After Endoscopic Submucosal Dissection for Gastric Neoplasm: Prospective Randomized Double-blind Placebo Controlled Study
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02401971	PHASE4	UNKNOWN	Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer
NCT02458573	PHASE4	COMPLETED	Comparison of the Effects of Continuous Epidural Analgesia and Continuous Intravenous Analgesia on Postoperative Bowel Movement in Patients Undergoing Laparoscopic Gastrectomy
NCT02638584	PHASE4	COMPLETED	Effects of Ilaprazole on Ulcer Healing Rate and Prevention of Gastrointestinal Bleeding in the Patients Undergone ESD.
NCT02776527	PHASE4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03550482	PHASE4	COMPLETED	Oncoxin® and Quality of Life in Cancer Patients
NCT03609892	PHASE4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03733639	PHASE4	UNKNOWN	Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
NCT04168346	PHASE4	NOT_YET_RECRUITING	Preoperative Intravenous Iron Therapy in Patients With Gastric Cancer
NCT04209933	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Different Bismuth Quadruple Therapies
NCT04591028	PHASE4	WITHDRAWN	A Study to Evaluate Indocyanine Green Lymphangiography to Improve Lymphadenectomy in Gastric Cancer Patients
NCT04607057	PHASE4	UNKNOWN	Supplemental Parenteral Nutrition During Postgastrectomy in Nutritionally at Risk Patient
NCT04660123	PHASE4	COMPLETED	A Real World Study of Bismuth Colloidal Pectin Granules Quadruple Therapy for H. Pylori Eradication
NCT04678492	PHASE4	COMPLETED	Helicobacter Rescue Therapy With High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy
NCT04697186	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Plus Amoxicillin Triple Therapy Versus Bismuth-containing Quadruple Therapy
NCT05029453	PHASE4	UNKNOWN	Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05354856	PHASE4	TERMINATED	The Effect of Chemoradiotherapy on Gastric Perfusion in Patients With Gastric Cancer.
NCT05410535	PHASE4	COMPLETED	To Evaluate Efficacy of Ursodeoxycholic Acid (UDCA) for the Prevention of Gallstone Formation After Gasterectomy
NCT05498766	PHASE4	NOT_YET_RECRUITING	Effect and Safety of Huaier Granule Versus SOX Regimen in Gastric Cancer Patients
NCT05518929	PHASE4	COMPLETED	Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients