CA12

Summary

CA12 (carbonic anhydrase 12, HGNC:1371) is a protein-coding gene on chromosome 15q22.2, encoding Carbonic anhydrase 12 (O43570). Reversible hydration of carbon dioxide.

Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. This gene product is a type I membrane protein that is highly expressed in normal tissues, such as kidney, colon and pancreas, and has been found to be overexpressed in 10% of clear cell renal carcinomas. Three transcript variants encoding different isoforms have been identified for this gene.

Source: NCBI Gene 771 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated hyperchlorhidrosis (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 128 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes — 67 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001218

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1371
Approved symbol	CA12
Name	carbonic anhydrase 12
Location	15q22.2
Locus type	gene with protein product
Status	Approved
Aliases	HsT18816
Ensembl gene	ENSG00000074410
Ensembl biotype	protein_coding
OMIM	603263
Entrez	771

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000178638, ENST00000344366, ENST00000422263, ENST00000558287, ENST00000560293, ENST00000560666, ENST00000907867, ENST00000907868, ENST00000907869, ENST00000907870, ENST00000925046

RefSeq mRNA: 3 — MANE Select: NM_001218 NM_001218, NM_001293642, NM_206925

CCDS: CCDS10185, CCDS10186, CCDS76767

Canonical transcript exons

ENST00000178638 — 11 exons

Exon	Start	End
ENSE00000449603	63340288	63340445
ENSE00000692799	63328098	63328130
ENSE00000692813	63342002	63342097
ENSE00000931536	63346530	63346709
ENSE00000931537	63345477	63345619
ENSE00001033986	63375658	63375678
ENSE00001106427	63338819	63338945
ENSE00001790531	63381636	63381846
ENSE00001820066	63321378	63326357
ENSE00003677117	63340720	63340783
ENSE00003682491	63327149	63327233

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 99.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7734 / max 1342.5410, expressed in 1146 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150416	24.1450	1127
150418	1.5265	611
150417	0.1019	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	99.71	gold quality
nephron tubule	UBERON:0001231	99.43	gold quality
cervix squamous epithelium	UBERON:0006922	99.30	gold quality
upper leg skin	UBERON:0004262	99.13	gold quality
choroid plexus epithelium	UBERON:0003911	98.97	gold quality
colonic mucosa	UBERON:0000317	98.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.85	gold quality
mammalian vulva	UBERON:0000997	98.73	gold quality
skin of hip	UBERON:0001554	98.59	gold quality
renal glomerulus	UBERON:0000074	98.25	gold quality
tongue squamous epithelium	UBERON:0006919	98.20	gold quality
pharyngeal mucosa	UBERON:0000355	98.19	gold quality
nipple	UBERON:0002030	98.08	gold quality
metanephric glomerulus	UBERON:0004736	98.05	gold quality
rectum	UBERON:0001052	97.87	gold quality
penis	UBERON:0000989	97.74	gold quality
mucosa of transverse colon	UBERON:0004991	97.73	gold quality
adult mammalian kidney	UBERON:0000082	97.70	gold quality
skin of abdomen	UBERON:0001416	97.57	gold quality
adult organism	UBERON:0007023	97.30	gold quality
cervix epithelium	UBERON:0004801	97.22	gold quality
squamous epithelium	UBERON:0006914	97.20	gold quality
zone of skin	UBERON:0000014	97.12	gold quality
skin of leg	UBERON:0001511	97.03	gold quality
oral cavity	UBERON:0000167	96.84	gold quality
esophagus squamous epithelium	UBERON:0006920	96.82	gold quality
gingiva	UBERON:0001828	96.59	gold quality
ganglionic eminence	UBERON:0004023	96.30	gold quality
gingival epithelium	UBERON:0001949	96.20	gold quality
epithelium of esophagus	UBERON:0001976	96.17	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	4331.44
E-CURD-119	yes	4248.21
E-GEOD-84465	yes	995.95
E-HCAD-10	yes	445.18
E-MTAB-10287	yes	45.78
E-GEOD-125970	yes	17.91
E-MTAB-6678	yes	8.07
E-CURD-135	no	1750.23
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, NR1I3, VHL

miRNA regulators (miRDB)

113 targeting CA12, 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-1252-5P	100.00	69.80	2774
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-518A-5P	99.70	69.01	2209

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 38)

• The non-pigmented ciliary epithelial cells from glaucoma eyes expressed higher levels of CAXII, which may be a targeted gene in glaucoma. (PMID:12676895)
• CA XII showed no or weak immunoreaction in the normal gastric mucosa and was slightly increased in gastric tumors. (PMID:12854129)
• The interplay between the functional von Hippel-Lindau tumor suppressor and CA IX/CA XII in colorectal tumors seems rather (PMID:15849821)
• CA12 mRNA expression was detected in 88.1% of cervical cancers. (PMID:16416108)
• CA XII is commonly expressed in diffuse astrocytomas and that it might be used as a biomarker of poor prognosis. (PMID:18322268)
• Carbonic anhydrase (CA) IX (and possibly also CA XII) participates in pH regulation, which is important for survival of hypoxic cancer cells. Both enzymes are therefore promising targetable therapeutic molecules. [Review] (PMID:18336315)
• Crucial role of ER in the regulation of the CA12 gene. (PMID:18451179)
• In embryonic and early fetal tissues; there is no evidence of co-localization of CAIX and CAXII; CAIX and CAXII expression is closely related to cell origin and secretory activity involving proton transport, respectively. (PMID:19291313)
• Data show that genes overexpressed in breast carcinoma including TFF1, TFF3, FOXA1 and CA12.Data show that genes overexpressed in breast carcinoma including TFF1, TFF3, FOXA1 and CA12. (PMID:20132413)
• Differential modulation of the active site environment of human carbonic anhydrase XII by cationic quantum dots and polylysine. (PMID:20215053)
• Suggest that CA XII should be considered a potential prognostic and therapeutic target in medulloblastomas and supratentorial primitive neuroectodermal tumours. (PMID:20398423)
• Carbonic anhydrase XII may affect the capability of invasion and migration of MDA-MB-231 cells, which may be mediated through the p38 MAPK pathway. (PMID:20434230)
• our results imply that CA2 and CA12 are highly over-expressed in advanced atherosclerosis by osteoclast-like cells of monocytic origin (PMID:20509747)
• we demonstrate that the hyperchlohidrosis phenotype is due to a homozygous mutation in CA12, encoding carbonic anhydrase XII. (PMID:21035102)
• CA12 may be used as a novel prognostic marker in combination with histologic grade of invasive cervical cancer. (PMID:21040567)
• Study identified the association of a Glu143Lys mutation in carbonic anhydrase 12 (CA12) with the disease. (PMID:21184099)
• The development of acidosis with topiramate and zonisamide is not determined by drug dose or by treatment duration, but may be influenced by polymorphisms in the gene for CA type XII. (PMID:21278619)
• The expression of CA XII in oral squamous cell carcinoma (OSCC) samples can predict the progression of OSCC and survival of OSCC patients. (PMID:22172588)
• Serum CAXII levels were significantly higher in lung cancer patients than in healthy controls, providing evidence that CAXII may be a novel sero-diagnostic marker for lung cancer. (PMID:22439015)
• an upregulation of CAXII in human T-cell acute lymphoblastic leukemia samples supporting the case that CAXII may represent a new therapeutic target for T-ALL/LL. (PMID:23348702)
• A critical role for re-oxygenation on CAIX and CAXII levels that may select for an aggressive lung cancer phenotype. (PMID:23910904)
• Suggest CAXII as a new secondary marker of the multidrug resistance phenotype that influences Pgp activity directly. (PMID:25686827)
• CAIX mRNA expression was significantly higher (p < 0.05) in hypoxia for all cell lines, which was in agreement with protein expression by ICC. CAXII expression was mixed, with a modest hypoxia-related increase in two cell lines (p < 0.05) and no change in others. (PMID:26276155)
• mutation CA12(E143K) causes mouth dryness disease due to aberrant CA12 glycosylation. (PMID:26486891)
• The expression of HIF-1alpha, but not HIF-2alpha, decreased in degenerated disc samples and was positively correlated with carbonic anhydrase 12 expression. (PMID:26901836)
• Our findings indicate that loss of CA XII function should be considered in individuals without CFTR mutations who exhibit CF-like features in the sweat gland and lung. (PMID:26911677)
• CA II and CA XII, but not CA VII or CA IX, could be useful in predicting survival in colorectal carcinomas (PMID:27688658)
• CAIX and CAXII expression are diagnostic for breast cancer subtype and prognosticators of patient survival. Overall, we show that CAIX but not CAXII drives growth, migration, and metastasis consistent with its expression in more aggressive breast cancers. (PMID:29965974)
• CAII, CAIX, and CAXII all have characteristic expression patterns in esophageal adenocarcinoma (EAC), its precursors and normal squamous epithelium. In EAC, CAII downregulation is associated with metastatic disease. CAIX expression is lost towards the more malignant lesions, but in lymph node positive disease, expression seems to be higher. CAXII is only expressed in normal esophageal epithelium. (PMID:30066203)
• Our results may contribute to further understand the physiology of Breast cancer (BC) cells and indicate that the Hh pathway controls Breast cancer (BC) cell migration and cell invasion also through CAXII, with important implications in identifying novel therapeutic targets. (PMID:30132883)
• CA12 plays vital roles in occurrence of congenital bilateral absence of vas deferens (PMID:30632488)
• CA12 was significant higher expressing in breast cancer tissues (PMID:30784287)
• Knockout of GLI1 and CAXII significantly decreased hallmarks of tumor aggressiveness including proliferation and migration. (PMID:31221477)
• Our newly identified humanized CA12-antibody with anti-cancer activity, represents a new tool for the treatment of CA12-positive tumors. (PMID:31366496)
• Carbonic Anhydrase XII Expression Is Modulated during Epithelial Mesenchymal Transition and Regulated through Protein Kinase C Signaling. (PMID:31979064)
• Carbonic anhydrase 12 gene silencing reverses the sensitivity of paclitaxel in drug-resistant breast cancer cells. (PMID:34696661)
• Carbonic anhydrase XII mediates the survival and prometastatic functions of macrophages in human hepatocellular carcinoma. (PMID:35362480)
• Trafficking of carbonic anhydrase 12 and bicarbonate transporters by histamine stimulation mediates intracellular acidic scenario in lung cancer cells. (PMID:37587861)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	ca12	ENSDARG00000045644
mus_musculus	Car12	ENSMUSG00000032373
rattus_norvegicus	Car12	ENSRNOG00000017766
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), CA2 (ENSG00000104267), 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 12 — O43570 (reviewed: O43570)

Alternative names: Carbonate dehydratase XII, Carbonic anhydrase XII, Tumor antigen HOM-RCC-3.1.3

All UniProt accessions (2): O43570, B3KUB4

UniProt curated annotations — full annotation on UniProt →

Function. Reversible hydration of carbon dioxide.

Subunit / interactions. Homodimer.

Subcellular location. Membrane. Cell membrane.

Tissue specificity. Highly expressed in colon, kidney, prostate, intestine and activated lymphocytes. Expressed at much higher levels in the renal cell cancers than in surrounding normal kidney tissue. Moderately expressed in pancreas, ovary and testis. Expressed in sweat glands and bronchiolar epithelium.

Disease relevance. Hyperchlorhidrosis, isolated (HYCHL) [MIM:143860] An autosomal recessive disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide (AZA), benzenesulfonamide and derivatives (4-carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene-sulfonamide ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4-aminoethylbenzene-sulfonamide) and Foscarnet (phosphonoformate trisodium salt).

Similarity. Belongs to the alpha-carbonic anhydrase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43570-1	1	yes
O43570-2	2

RefSeq proteins (3): NP_001209, NP_001280571, NP_996808 (=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 (46 total): strand 16, helix 9, binding site 4, glycosylation site 3, sequence variant 2, topological domain 2, turn 2, signal peptide 1, chain 1, disulfide bond 1, splice variant 1, sequence conflict 1, transmembrane region 1, domain 1, active site 1

Structure

Experimental structures (PDB)

40 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9F2O	X-RAY DIFFRACTION	1.12
9F30	X-RAY DIFFRACTION	1.12
9FN7	X-RAY DIFFRACTION	1.12
9R0U	X-RAY DIFFRACTION	1.19
5MSA	X-RAY DIFFRACTION	1.2
6G5L	X-RAY DIFFRACTION	1.21
9F2N	X-RAY DIFFRACTION	1.21
9F3G	X-RAY DIFFRACTION	1.21
9FN8	X-RAY DIFFRACTION	1.21
9R31	X-RAY DIFFRACTION	1.25
5MSB	X-RAY DIFFRACTION	1.3
6R6Y	X-RAY DIFFRACTION	1.38
7PUV	X-RAY DIFFRACTION	1.4
4WW8	X-RAY DIFFRACTION	1.42
5LL5	X-RAY DIFFRACTION	1.42
6G7A	X-RAY DIFFRACTION	1.42
7PUW	X-RAY DIFFRACTION	1.42
4HT2	X-RAY DIFFRACTION	1.45
4KP5	X-RAY DIFFRACTION	1.45
5LL9	X-RAY DIFFRACTION	1.45
9R0L	X-RAY DIFFRACTION	1.45
5LLP	X-RAY DIFFRACTION	1.48
1JD0	X-RAY DIFFRACTION	1.5
6T5P	X-RAY DIFFRACTION	1.5
7PUU	X-RAY DIFFRACTION	1.51
6QNL	X-RAY DIFFRACTION	1.53
1JCZ	X-RAY DIFFRACTION	1.55
4QJ0	X-RAY DIFFRACTION	1.55
4QJW	X-RAY DIFFRACTION	1.55
5LLO	X-RAY DIFFRACTION	1.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43570-F1	88.50	0.77

Antibody-complex structures (SAbDab): 1 — 6RPS

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): 94 (proton donor/acceptor)

Ligand- & substrate-binding residues (4): 226–227; 119; 121; 145

Disulfide bonds (1): 50–230

Glycosylation sites (3): 28, 80, 162

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1475029	Reversible hydration of carbon dioxide
R-HSA-1430728	Metabolism

MSigDB gene sets: 291 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, MCLACHLAN_DENTAL_CARIES_UP, HARRIS_HYPOXIA, GOMF_CARBONATE_DEHYDRATASE_ACTIVITY, JAEGER_METASTASIS_DN, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, BILD_SRC_ONCOGENIC_SIGNATURE, STOSSI_RESPONSE_TO_ESTRADIOL, MODULE_59, MODULE_66, WEI_MYCN_TARGETS_WITH_E_BOX, BROWNE_HCMV_INFECTION_48HR_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN

GO Biological Process (2): estrous cycle (GO:0044849), chloride ion homeostasis (GO:0055064)

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

GO Cellular Component (4): plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma membrane region	2
ovulation cycle	1
monoatomic anion homeostasis	1
inorganic ion homeostasis	1
hydro-lyase activity	1
transition metal ion binding	1
catalytic activity	1
cation binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1
basal plasma membrane	1
apical part of cell	1

Protein interactions and networks

STRING

1556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CA12	CYP24A1	Q07973	799
CA12	SLC9A1	P19634	640
CA12	SLC4A2	P04920	632
CA12	SLC2A1	P11166	571
CA12	VHL	P40337	556
CA12	ALB	P02768	550
CA12	HIF1AN	Q9NWT6	539
CA12	EPAS1	Q99814	533
CA12	SLC4A4	Q9Y6R1	528
CA12	SLC16A4	O15374	507
CA12	SLC16A3	O15427	507
CA12	SLC4A7	Q9Y6M7	500
CA12	FOXF1	Q12946	499
CA12	ELOA2	Q8IYF1	495
CA12	TG	P01266	491

IntAct

21 interactions, top by confidence:

A	B	Type	Score
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
FLVCR1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
DAXX	CA12	psi-mi:“MI:0915”(physical association)	0.370
MAPK6	CA12	psi-mi:“MI:0915”(physical association)	0.370
RDH11	CA12	psi-mi:“MI:0915”(physical association)	0.370
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
rep	CA12	psi-mi:“MI:0914”(association)	0.350
CLRN2	CA12	psi-mi:“MI:0914”(association)	0.350
SLC44A1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
SLC7A10	MYO1C	psi-mi:“MI:0914”(association)	0.350
SLCO1B3	SNAP23	psi-mi:“MI:0914”(association)	0.350
SGSM2	CA12	psi-mi:“MI:0915”(physical association)	0.000
ATP5F1C	CA12	psi-mi:“MI:0915”(physical association)	0.000
CUX1	CA12	psi-mi:“MI:0915”(physical association)	0.000
KATNBL1	CA12	psi-mi:“MI:0915”(physical association)	0.000
CA12	LGALS7	psi-mi:“MI:0915”(physical association)	0.000
MRPL9	CA12	psi-mi:“MI:0915”(physical association)	0.000
TOE1	CA12	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (36): CA12 (Synthetic Lethality), CA12 (Affinity Capture-MS), CA12 (Affinity Capture-MS), CA12 (Affinity Capture-MS), CA12 (Two-hybrid), CA12 (Two-hybrid), CA12 (Affinity Capture-MS), CA12 (Affinity Capture-MS), CA12 (Affinity Capture-MS), CA12 (Affinity Capture-MS), CA12 (Proximity Label-MS), CA12 (Proximity Label-MS), CA12 (Proximity Label-MS), CA12 (Proximity Label-MS), CA12 (Proximity Label-MS)

ESM2 similar proteins: A0A7H0DN92, A0JN41, A7MAQ2, F4HUC4, F4IHR4, F4JIK2, O04846, O43570, O57211, P04195, P08060, P0DO50, P0DSY1, P0DSY2, P10731, P12890, P18761, P18915, P19021, P20508, P23280, P28651, P35219, P48284, P61215, P97467, Q10462, Q18932, Q20781, Q5PPN4, Q5R4U0, Q5TZ24, Q64444, Q68CI2, Q6RZI9, Q75N34, Q75N35, Q84UV8, Q865C0, Q866X6

Diamond homologs: A0A7H0DN92, A0JN41, B8V7P3, O43570, O57211, O70354, O75493, P00915, P00916, P00918, P00919, P00920, P00921, P00922, P04195, P07450, P07451, P07630, P0DSY1, P0DSY2, P14141, P16015, P20508, P23589, P27139, P28651, P35217, P35218, P35219, P43165, P43166, P48282, P61215, P83299, Q18932, Q1LZA1, Q5PPN4, Q5R4U0, Q5R665, Q5S1S4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	60
Likely benign	13
Benign	30

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
218367	NM_001218.5(CA12):c.859_860insACCT (p.Thr287fs)	Pathogenic
218368	NM_001218.5(CA12):c.363C>A (p.His121Gln)	Pathogenic
18442	NM_001218.5(CA12):c.427G>A (p.Glu143Lys)	Likely pathogenic
3893023	NM_001218.5(CA12):c.686del (p.Pro229fs)	Likely pathogenic
561267	NM_001218.5(CA12):c.956_957del (p.Val319fs)	Likely pathogenic

SpliceAI

1713 predictions. Top by Δscore:

Variant	Effect	Δscore
15:63338815:TCA:T	donor_loss	1.0000
15:63338818:C:CG	donor_loss	1.0000
15:63340446:C:CC	acceptor_gain	1.0000
15:63340446:CTAG:C	acceptor_loss	1.0000
15:63340447:T:C	acceptor_loss	1.0000
15:63340779:CCCAT:C	acceptor_gain	1.0000
15:63340780:CCAT:C	acceptor_gain	1.0000
15:63340780:CCATC:C	acceptor_gain	1.0000
15:63340781:CAT:C	acceptor_gain	1.0000
15:63340781:CATC:C	acceptor_gain	1.0000
15:63340784:C:A	acceptor_loss	1.0000
15:63340784:C:CC	acceptor_gain	1.0000
15:63340785:T:G	acceptor_loss	1.0000
15:63341996:TCTTA:T	donor_loss	1.0000
15:63341997:CTTA:C	donor_loss	1.0000
15:63341998:TTACC:T	donor_loss	1.0000
15:63341999:TACC:T	donor_loss	1.0000
15:63342001:C:A	donor_loss	1.0000
15:63342098:C:CC	acceptor_gain	1.0000
15:63345473:TTAC:T	donor_loss	1.0000
15:63345474:TA:T	donor_loss	1.0000
15:63345475:A:AC	donor_gain	1.0000
15:63345475:AC:A	donor_gain	1.0000
15:63345475:ACCT:A	donor_gain	1.0000
15:63345476:C:CA	donor_gain	1.0000
15:63345476:CC:C	donor_gain	1.0000
15:63345476:CCT:C	donor_gain	1.0000
15:63345476:CCTC:C	donor_gain	1.0000
15:63345476:CCTCG:C	donor_gain	1.0000
15:63345615:CTTCA:C	acceptor_gain	1.0000

AlphaMissense

2315 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:63340329:A:G	W236R	0.997
15:63340329:A:T	W236R	0.997
15:63340376:C:G	R220P	0.996
15:63340327:C:A	W236C	0.995
15:63340327:C:G	W236C	0.995
15:63340345:G:C	C230W	0.995
15:63340346:C:T	C230Y	0.995
15:63340368:C:A	G223W	0.995
15:63342096:A:G	L144P	0.994
15:63346646:G:T	P57H	0.994
15:63346687:C:A	W43C	0.994
15:63346687:C:G	W43C	0.994
15:63340346:C:G	C230S	0.993
15:63340347:A:T	C230S	0.993
15:63340368:C:G	G223R	0.993
15:63340368:C:T	G223R	0.993
15:63345545:G:C	H121D	0.993
15:63338869:C:G	R275P	0.992
15:63338870:G:C	R275G	0.992
15:63340346:C:A	C230F	0.992
15:63345481:G:T	A142D	0.992
15:63345515:A:G	S131P	0.992
15:63345553:A:G	L118P	0.992
15:63340367:C:T	G223E	0.991
15:63345511:T:A	E132V	0.991
15:63340322:A:T	V238D	0.990
15:63340347:A:G	C230R	0.990
15:63342016:C:G	A171P	0.990
15:63345482:C:G	A142P	0.990
15:63345542:A:G	W122R	0.990

dbSNP variants (sampled 300 via entrez): RS1000050632 (15:63347977 A>G,T), RS1000146184 (15:63361387 A>G), RS1000154834 (15:63321596 CG>C), RS1000202262 (15:63357891 C>T), RS1000211998 (15:63367862 T>C), RS1000268709 (15:63327639 T>C), RS1000345603 (15:63363942 C>G,T), RS1000406887 (15:63324556 A>T), RS1000415306 (15:63355509 T>C), RS1000458163 (15:63336372 T>C), RS1000464077 (15:63369753 G>C), RS1000569111 (15:63321284 G>A), RS1000596778 (15:63358316 C>T), RS1000668605 (15:63352488 G>A), RS1000743799 (15:63324926 A>G)

Disease associations

OMIM: gene MIM:603263 | disease phenotypes: MIM:143860

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated hyperchlorhidrosis	Strong	Autosomal recessive

Mondo (1): isolated hyperchlorhidrosis (MONDO:0007747)

Orphanet (1): Isolated hyperchlorhidrosis (Orphanet:542657)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001508	Failure to thrive
HP:0002153	Hyperkalemia
HP:0002902	Hyponatremia
HP:0003593	Infantile onset
HP:0004906	Hypernatremic dehydration
HP:0011968	Feeding difficulties
HP:0012236	Elevated sweat chloride

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST008295_42	Number of decayed, missing and filled tooth surfaces or use of dentures	1.000000e-26
GCST008302_2	Number of decayed, missing and filled tooth surfaces	2.000000e-08
GCST008306_4	Dentures	5.000000e-21
GCST010002_172	Refractive error	6.000000e-36
GCST011494_66	Daytime nap	8.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010078	dentures
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095180 (PROTEIN FAMILY), CHEMBL3242 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

67 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,588,117 (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
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	13,120
CHEMBL35	FUROSEMIDE	4
CHEMBL406	INDAPAMIDE	4
CHEMBL419	MAFENIDE	4
CHEMBL424	SALICYLIC ACID	4
CHEMBL4303669	ZOLEDRONIC ACID	4
CHEMBL477772	PAZOPANIB	4
CHEMBL537	HYDROQUINONE	4
CHEMBL58323	LACOSAMIDE	4
CHEMBL609	TRIENTINE	4
CHEMBL6466	COUMARIN	4

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2306719	Other	3	topiramate;zonisamide
rs4984241	Other	3	topiramate;zonisamide

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2306719	CA12	3	0.00	1	topiramate;zonisamide
rs4984241	CA12	3	0.00	1	topiramate;zonisamide

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Carbonic anhydrases

Most potent curated ligand interactions (19 total), top 19:

Ligand	Action	Affinity	Parameter
brinzolamide	Inhibition	8.52	pKi
methazolamide	Inhibition	8.47	pKi
indisulam	Inhibition	8.47	pKi
dorzolamide	Inhibition	8.46	pKi
benzolamide	Inhibition	8.46	pKi
topiramate	Inhibition	8.42	pKi
sulpiride	Inhibition	8.41	pKi
SLC-0111	Inhibition	8.35	pKi
chlorthalidone	Inhibition	8.35	pKi
acetazolamide	Inhibition	8.24	pKi
compound 11 [PMID: 41150938]	Inhibition	8.14	pKi
valdecoxib	Inhibition	7.89	pKi
celecoxib	Inhibition	7.74	pKi
ethoxzolamide	Inhibition	7.66	pKi
salvianolic acid A	Inhibition	7.4	pKi
diclofenamide	Inhibition	7.3	pKi
compound 5a [PMID: 31287314]	Inhibition	6.11	pKi
compound 5b [PMID: 31287314]	Inhibition	5.0	pKi
zonisamide	Inhibition	4.96	pKi

Binding affinities (BindingDB)

124 measured of 147 human assays (168 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid	EC50	0.0469 nM
2-Chloro-4-{[2-(methylthio)-1H-benzimidazol-1-yl]acetyl}-benzenesulfonamide (2j)	KD	1.67 nM
2-Chloro-4-[(2-propyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (2f)	KD	2.86 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
4-[(2-Butyl-1H-benzimidazol-1-yl)acetyl]-2-chlorobenzenesulfonamide (2g)	KD	3.33 nM
4-{[2-(Methylsulfanyl)-1H-benzimidazol-1-yl]acetyl}benzenesulfonamide (1j)	KD	3.57 nM
aliphatic sulfamate, 1	KI	3.7 nM
4-[(2-Isopropyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (1h)	KD	4 nM
2-Chloro-4-[(2-ethyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (2e)	KD	4.76 nM
2-Chloro-4-[(2-isopropyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (2h)	KD	5 nM
2-Chloro-4-[(2-methyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (2b)	KD	5.88 nM
2-Chloro-4-[(2-isobutyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (2i)	KD	6.67 nM
CHEMBL2348439	KI	7.1 nM
4-[(2-Propyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (1f)	KD	7.14 nM
4-{[2-(Hydroxymethyl)-1H-benzimidazol-1-yl]acetyl}benzenesulfonamide (1c)	KD	8.33 nM
4-[(2-Benzyl-1H-benzimidazol-1-yl)acetyl]-2-chlorobenzenesulfonamide (2d)	KD	8.33 nM
4-[(2-Ethyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (1e)	KD	8.33 nM
4-[(2-Isobutyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (1i)	KD	8.33 nM
4-[(2-Methyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (1b)	KD	10 nM
2-Chloro-4-{[2-(hydroxymethyl)-1H-benzimidazol-1-yl]acetyl}benzenesulfonamide (2c)	KD	10 nM
4-[(2-Butyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (1g)	KD	11.1 nM
4-(1H-benzimidazol-1-ylacetyl)-2-chlorobenzenesulfonamide (2a)	KD	12 nM
4-(1H-benzimidazol-1-ylacetyl)benzenesulfonamide (1a)	KD	33 nM
4-(3-quinolinyl)-benzenesulfonamide (4p)	KI	35 nM
4-(phenyl)-bezenesulfonamide (4a)	KI	42 nM
N-(3-morpholinopropyl)benzene-1,4-disulfonamide (I-2)	IC50	57.7 nM
N-(4-diethylaminoethoxybenzyl)benzene-1,4-bis-sulfonamide (I-3)	IC50	59.8 nM
1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-3-[2-(4-sulfamoylphenyl)ethyl]thiourea	KI	79 nM	US-8980932: Cancer targeting using carbonic anhydrase isoform IX inhibitors
2-(2-nitroimidazol-1-yl)-N-[2-(4-sulfamoylphenyl)ethyl]acetamide	KI	79 nM	US-8980932: Cancer targeting using carbonic anhydrase isoform IX inhibitors
1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-3-(3-sulfamoylphenyl)thiourea	KI	84 nM	US-8980932: Cancer targeting using carbonic anhydrase isoform IX inhibitors
azo-sulfonamide, 1b	KI	95 nM
azo-sulfonamide, 2a	KI	95 nM
azo-sulfonamide, 1f	KI	96 nM
azo-sulfonamide, 2b	KI	96 nM
2-(2-nitroimidazol-1-yl)-N-(3-sulfamoylphenyl)acetamide	KI	101 nM	US-8980932: Cancer targeting using carbonic anhydrase isoform IX inhibitors
1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-3-(4-sulfamoylphenyl)thiourea	KI	105 nM	US-8980932: Cancer targeting using carbonic anhydrase isoform IX inhibitors
azo-sulfonamide, 1e	KI	106 nM
2-(2-nitroimidazol-1-yl)-N-[(4-sulfamoylphenyl)methyl]acetamide	KI	107 nM	US-8980932: Cancer targeting using carbonic anhydrase isoform IX inhibitors
2-(hydrazinecarbonyl)-3-(2-methylphenyl)-1H-indole-5-sulfonamide	KI	107 nM
3-(2-bromophenyl)-2-(hydrazinecarbonyl)-1H-indole-5-sulfonamide	KI	110 nM
azo-sulfonamide, 2d	KI	113 nM
3-[(2-Isobutyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (3i)	KD	125 nM
4-[(2-Benzyl-1H-benzimidazol-1-yl)acetyl]benzenesulfonamide (1d)	KD	143 nM
1-(2,6-difluorophenyl)-3-(4-sulfamoylphenyl)urea	KI	158 nM	US-9962398: Sulfonamide compounds for inhibition of metastatic tumor growth
1-(3-chlorophenyl)-3-(4-sulfamoylphenyl)urea	KI	158 nM	US-9962398: Sulfonamide compounds for inhibition of metastatic tumor growth
azo-sulfonamide, 1c	KI	170 nM
1-[2-chloro-4-(trifluoromethyl)phenyl]-3-(4-sulfamoylphenyl)urea	KI	192 nM	US-9962398: Sulfonamide compounds for inhibition of metastatic tumor growth
4-Sulfamoyl-N-(3-morpholinopropyl)benzamide (I-1)	IC50	231 nM
Topiramate, 3	KI	250 nM
1-(2,4-difluorophenyl)-3-(4-sulfamoylphenyl)urea	KI	275 nM	US-9962398: Sulfonamide compounds for inhibition of metastatic tumor growth

ChEMBL bioactivities

5803 potent at pChembl≥5 of 5925 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Kd	0.01	nM	CHEMBL4586089
11.00	Kd	0.01	nM	CHEMBL4470832
11.00	Kd	0.01	nM	CHEMBL4436290
10.89	Kd	0.013	nM	CHEMBL4165543
10.85	Kd	0.014	nM	CHEMBL4162451
10.72	Kd	0.019	nM	CHEMBL4176828
10.72	Kd	0.019	nM	CHEMBL4445515
10.70	Kd	0.02	nM	CHEMBL4553519
10.70	Kd	0.02	nM	CHEMBL4565224
10.70	Kd	0.02	nM	CHEMBL4572161
10.64	Kd	0.023	nM	CHEMBL4177268
10.52	Kd	0.03	nM	CHEMBL4465972
10.52	Kd	0.03	nM	CHEMBL4515586
10.52	Kd	0.03	nM	CHEMBL4521683
10.51	Kd	0.031	nM	CHEMBL4170792
10.40	Kd	0.04	nM	CHEMBL4543024
10.40	Kd	0.04	nM	CHEMBL4565560
10.39	Kd	0.041	nM	CHEMBL4168966
10.35	Kd	0.045	nM	CHEMBL3359181
10.30	Kd	0.05	nM	CHEMBL4450306
10.22	Kd	0.06	nM	CHEMBL4463844
10.22	Kd	0.06	nM	CHEMBL4583164
10.15	Kd	0.07	nM	CHEMBL4456084
10.15	Kd	0.07	nM	CHEMBL4468310
10.15	Kd	0.07	nM	CHEMBL4576689
10.11	Kd	0.077	nM	CHEMBL4170371
10.09	Kd	0.081	nM	CHEMBL4163518
10.09	Kd	0.081	nM	CHEMBL4176862
10.00	Kd	0.1	nM	CHEMBL4456851
10.00	Kd	0.1	nM	CHEMBL4454599
10.00	Ki	0.1	nM	CHEMBL1271639
9.92	Kd	0.12	nM	CHEMBL4443095
9.92	Kd	0.12	nM	CHEMBL4592616
9.92	Kd	0.12	nM	CHEMBL4517317
9.89	Kd	0.13	nM	CHEMBL4551069
9.85	Kd	0.14	nM	CHEMBL4566236
9.82	Kd	0.15	nM	CHEMBL4517728
9.80	Kd	0.16	nM	CHEMBL4578934
9.80	Kd	0.16	nM	CHEMBL4558287
9.80	Kd	0.16	nM	CHEMBL4573963
9.74	Kd	0.18	nM	CHEMBL4464359
9.70	Kd	0.2	nM	CHEMBL4451503
9.70	Kd	0.2	nM	CHEMBL4168586
9.70	Ki	0.2	nM	CHEMBL4552380
9.70	Ki	0.2	nM	CHEMBL4460315
9.70	Ki	0.2	nM	CHEMBL4434661
9.70	Ki	0.2	nM	CHEMBL282157
9.68	Kd	0.21	nM	CHEMBL4166643
9.68	Kd	0.21	nM	CHEMBL4168586
9.62	Ki	0.24	nM	CHEMBL2402776

PubChem BioAssay actives

4956 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-N-(2-hydroxyethyl)-2-phenylsulfanyl-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-(cyclohexylamino)-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1361390: Binding affinity to recombinant human carbonic anhydrase 12 (30 to 291 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-(cyclohexylamino)-N-(2-methoxyethyl)-5-sulfamoylbenzamide	1361395: Binding affinity to recombinant human carbonic anhydrase 12 (30 to 291 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain assessed as intrinsic Kd by by isothermal titration calorimetry	kd	<0.0001	uM
4-bromo-N-butyl-2-(cyclohexylamino)-5-sulfamoylbenzamide	1361390: Binding affinity to recombinant human carbonic anhydrase 12 (30 to 291 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzylamino)-4-chloro-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1361390: Binding affinity to recombinant human carbonic anhydrase 12 (30 to 291 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-2-cyclohexylsulfanyl-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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-hydroxyethylsulfanyl)-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-butyl-2-phenylsulfanyl-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-bromo-N-(2-hydroxyethyl)-2-phenylsulfanyl-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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-hydroxyethyl)-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-cyclohexylsulfanyl-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1361390: Binding affinity to recombinant human carbonic anhydrase 12 (30 to 291 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-(cyclohexylamino)-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1361395: Binding affinity to recombinant human carbonic anhydrase 12 (30 to 291 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain assessed as intrinsic Kd by by isothermal titration calorimetry	kd	<0.0001	uM
4-[(2-benzylsulfanyl-4-chloro-5-sulfamoylbenzoyl)amino]butanoic acid	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
methyl 4-[(4-chloro-2-phenylsulfanyl-5-sulfamoylbenzoyl)amino]butanoate	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-phenylsulfanyl-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzoic acid	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-[(4-chloro-2-phenylsulfanyl-5-sulfamoylbenzoyl)amino]butanoic acid	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2-(benzenesulfonyl)-4-chloro-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0001	uM
2-(benzenesulfonyl)-4-chloro-N-(2-methoxyethyl)-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1361390: Binding affinity to recombinant human carbonic anhydrase 12 (30 to 291 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1361390: Binding affinity to recombinant human carbonic anhydrase 12 (30 to 291 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	0.0001	uM
N-butyl-4-chloro-2-cyclohexylsulfonyl-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0001	uM
2-(benzenesulfinyl)-4-bromo-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 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	1361390: Binding affinity to recombinant human carbonic anhydrase 12 (30 to 291 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain 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	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0001	uM
4-bromo-N-butyl-2-cyclohexylsulfonyl-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0001	uM
4-chloro-N-cyclohexyl-2-cyclohexylsulfanyl-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0001	uM
2-(benzenesulfonyl)-4-chloro-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520088: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, increases expression, affects expression, affects cotreatment, decreases expression (+1 more)	15
bisphenol A	affects cotreatment, increases methylation, increases expression, affects expression, decreases expression	11
Valproic Acid	increases expression, affects cotreatment	7
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression, affects binding, increases reaction	6
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	5
Genistein	decreases reaction, increases expression, increases reaction	5
Benzo(a)pyrene	affects expression, affects methylation, increases expression	4
Fulvestrant	affects cotreatment, increases methylation, decreases reaction, increases expression, increases reaction (+1 more)	3
Oxygen	decreases reaction, increases expression	3
Raloxifene Hydrochloride	affects expression, affects cotreatment, increases expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetazolamide	affects binding, decreases activity	2
Air Pollutants	decreases expression, increases abundance	2
Dexamethasone	decreases reaction, increases expression, increases reaction, affects cotreatment, decreases expression	2
Smoke	decreases expression, increases expression	2
Tamoxifen	affects expression, affects cotreatment, increases expression, decreases expression	2
Zearalenone	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
SLC-0111	decreases activity	1
methyleugenol	increases expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
methylumbelliferyl-alpha-D-mannopyranoside	decreases activity	1
oryzalin	affects binding, decreases activity	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1

ChEMBL screening assays

530 unique, capped per target: 526 binding, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3386760	Binding	Inhibition of carbonic anhydrase (unknown origin)	Substituted thieno[2,3-b]thiophenes and related congeners: Synthesis, β-glucuronidase inhibition activity, crystal structure, and POM analyses. — Bioorg Med Chem
CHEMBL4187340	ADMET	Binding affinity to recombinant human carbonic anhydrase 12 (1 to 260 residues) expressed in Escherichia coli BL21 (DE3) in presence of ANS by fluorescent thermal shift assay	Benzimidazole design, synthesis, and docking to build selective carbonic anhydrase VA inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1EQ	Abcam A-549 CA12 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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