CA4

Summary

CA4 (carbonic anhydrase 4, HGNC:1375) is a protein-coding gene on chromosome 17q23.1, encoding Carbonic anhydrase 4 (P22748). Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH.

Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. This gene encodes a glycosylphosphatidyl-inositol-anchored membrane isozyme expressed on the luminal surfaces of pulmonary (and certain other) capillaries and proximal renal tubules. Its exact function is not known; however, it may have a role in inherited renal abnormalities of bicarbonate transport.

Source: NCBI Gene 762 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa 17 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 374 total — 6 pathogenic, 10 likely-pathogenic (top 9% of genes corpus-wide)
• GTEx eGene: eQTL in 13 tissues, sQTL in 7 (q < 0.05)
• Phenotypes (HPO): 31
• Drug target: yes — 4 curated mechanism-of-action drugs; 59 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 4 — Acetazolamide, Dichlorphenamide, Methazolamide, +1 more
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.97 (unconstrained)
• MANE Select transcript: NM_000717
• Interaction hub: 1,884 STRING partners (top 9% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1375
Approved symbol	CA4
Name	carbonic anhydrase 4
Location	17q23.1
Locus type	gene with protein product
Status	Approved
Aliases	CAIV, Car4
Ensembl gene	ENSG00000167434
Ensembl biotype	protein_coding
OMIM	114760
Entrez	762

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 16 protein_coding, 8 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000300900

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 4

ENST00000300900, ENST00000585705, ENST00000586876, ENST00000587265, ENST00000590203, ENST00000591725, ENST00000904866, ENST00000904867, ENST00000904868, ENST00000904869, ENST00000904870, ENST00000904871, ENST00000957246, ENST00000957247, ENST00001002724, ENST00001043695, ENST00001043696, ENST00001043697, ENST00001110704, ENST00001120385, ENST00001120386, ENST00001120387, ENST00001120388, ENST00001127033, ENST00001140508

RefSeq mRNA: 1 — MANE Select: NM_000717 NM_000717

CCDS: CCDS11624

Canonical transcript exons

ENST00000300900 — 8 exons

Exon	Start	End
ENSE00001112954	60157690	60157788
ENSE00001112955	60157427	60157572
ENSE00002745558	60159230	60159546
ENSE00002807999	60149973	60150092
ENSE00003477864	60155314	60155367
ENSE00003563073	60158061	60158127
ENSE00003643831	60156560	60156715
ENSE00003660115	60158283	60158446

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 99.40.

FANTOM5 (CAGE): breadth broad, TPM avg 4.1151 / max 437.2886, expressed in 376 samples.

Highest expression (Bgee): mucosa of transverse colon, rectum, cerebellar hemisphere, cerebellar cortex, hemisphere of cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CA4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Visceral Omentum	sqtl	2.1e-12	+0.95	17:60157982:C:T
Brain Cerebellum	sqtl	1.5e-11	-1.10	17:60156793:A:T
Brain Frontal Cortex BA9	eqtl	4.1e-07	-0.52	17:60373548:AT:A
Brain Cortex	eqtl	6.4e-06	-0.57	17:60191995:A:AACTT
Thyroid	sqtl	8.4e-06	-0.74	17:60157982:C:T
Lung	sqtl	1.1e-04	+0.69	17:60157982:C:T
Adipose Subcutaneous	sqtl	4.0e-04	-0.52	17:60156155:A:G
Brain Cerebellar Hemisphere	sqtl	6.3e-04	+1.32	17:60157982:C:T
Whole Blood	eqtl	7.1e-04	-0.20	17:60422864:T:G
Skin Sun Exposed Lower leg	eqtl	1.2e-03	+0.25	17:60130051:A:G
Skin Not Sun Exposed Suprapubic	eqtl	1.6e-03	-0.17	17:60505177:C:T
Heart Left Ventricle	eqtl	3.6e-03	-0.40	17:60257287:C:G
Spleen	eqtl	1.2e-02	-0.41	17:60574425:G:A
Brain Anterior cingulate cortex BA24	eqtl	1.5e-02	-0.41	17:60193734:T:C
Esophagus Muscularis	eqtl	1.7e-02	-0.36	17:60416843:C:T
Brain Putamen basal ganglia	eqtl	2.8e-02	-0.43	17:59404474:A:T
Heart Atrial Appendage	eqtl	3.3e-02	-0.40	17:60306633:G:A
Whole Blood	sqtl	3.6e-02	+0.37	17:60157982:C:T
Esophagus Mucosa	eqtl	4.1e-02	-0.28	17:60437127:C:CGT
Nerve Tibial	eqtl	4.2e-02	-0.14	17:59312932:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
162040	3.4261	353
162039	0.6890	201

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.40	gold quality
rectum	UBERON:0001052	98.36	gold quality
cerebellar hemisphere	UBERON:0002245	98.33	gold quality
cerebellar cortex	UBERON:0002129	98.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.21	gold quality
right lung	UBERON:0002167	97.60	gold quality
cerebellum	UBERON:0002037	97.31	gold quality
colonic mucosa	UBERON:0000317	96.31	gold quality
paraflocculus	UBERON:0005351	96.10	gold quality
left lobe of thyroid gland	UBERON:0001120	95.88	gold quality
upper lobe of left lung	UBERON:0008952	95.80	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.34	gold quality
omental fat pad	UBERON:0010414	95.04	gold quality
peritoneum	UBERON:0002358	94.97	gold quality
upper lobe of lung	UBERON:0008948	94.97	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.85	gold quality
thyroid gland	UBERON:0002046	94.59	gold quality
cerebellar vermis	UBERON:0004720	94.26	gold quality
apex of heart	UBERON:0002098	93.49	gold quality
right lobe of thyroid gland	UBERON:0001119	93.25	gold quality
transverse colon	UBERON:0001157	92.54	gold quality
adipose tissue	UBERON:0001013	91.79	gold quality
right frontal lobe	UBERON:0002810	91.00	gold quality
lung	UBERON:0002048	90.84	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.36	gold quality
connective tissue	UBERON:0002384	90.31	gold quality
adult mammalian kidney	UBERON:0000082	90.22	gold quality
heart left ventricle	UBERON:0002084	90.19	gold quality
body of pancreas	UBERON:0001150	90.04	gold quality
cardiac ventricle	UBERON:0002082	89.92	gold quality
frontal pole	UBERON:0002795	89.82	gold quality
adult organism	UBERON:0007023	89.50	gold quality
corpus epididymis	UBERON:0004359	89.40	gold quality
gall bladder	UBERON:0002110	88.79	gold quality
blood	UBERON:0000178	88.75	gold quality
metanephros cortex	UBERON:0010533	87.34	gold quality
prefrontal cortex	UBERON:0000451	87.30	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.79	gold quality
adenohypophysis	UBERON:0002196	86.33	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.23	gold quality
ileal mucosa	UBERON:0000331	86.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.00	gold quality
large intestine	UBERON:0000059	85.95	gold quality
vena cava	UBERON:0004087	85.77	gold quality
colon	UBERON:0001155	85.55	gold quality
heart	UBERON:0000948	85.22	gold quality
cauda epididymis	UBERON:0004360	85.09	gold quality
seminal vesicle	UBERON:0000998	85.04	gold quality
cingulate cortex	UBERON:0003027	84.95	gold quality
frontal cortex	UBERON:0001870	84.89	gold quality
anterior cingulate cortex	UBERON:0009835	84.86	gold quality
lower lobe of lung	UBERON:0008949	84.70	gold quality
Brodmann (1909) area 10	UBERON:0013541	84.38	gold quality
kidney	UBERON:0002113	84.34	gold quality
neocortex	UBERON:0001950	83.43	gold quality
pituitary gland	UBERON:0000007	83.24	gold quality
intestine	UBERON:0000160	82.59	gold quality
pancreas	UBERON:0001264	82.27	gold quality
triceps brachii	UBERON:0001509	82.14	silver quality
right atrium auricular region	UBERON:0006631	82.11	gold quality
cerebral cortex	UBERON:0000956	81.86	gold quality
colonic epithelium	UBERON:0000397	81.82	gold quality
bone marrow	UBERON:0002371	81.80	gold quality
brain	UBERON:0000955	81.63	gold quality
spleen	UBERON:0002106	81.63	gold quality
central nervous system	UBERON:0001017	81.50	gold quality
cardiac atrium	UBERON:0002081	81.47	gold quality
putamen	UBERON:0001874	81.27	gold quality
amygdala	UBERON:0001876	80.84	gold quality
muscle of leg	UBERON:0001383	80.79	gold quality
gastrocnemius	UBERON:0001388	80.71	gold quality
muscle organ	UBERON:0001630	80.55	gold quality
vastus lateralis	UBERON:0001379	80.52	silver quality
telencephalon	UBERON:0001893	80.30	gold quality
quadriceps femoris	UBERON:0001377	80.24	silver quality
forebrain	UBERON:0001890	80.15	gold quality
nephron tubule	UBERON:0001231	79.90	gold quality
heart right ventricle	UBERON:0002080	79.81	gold quality
middle frontal gyrus	UBERON:0002702	79.66	gold quality
skeletal muscle tissue	UBERON:0001134	79.50	gold quality
body of stomach	UBERON:0001161	79.39	gold quality
cortex of kidney	UBERON:0001225	79.29	gold quality
orbitofrontal cortex	UBERON:0004167	79.21	gold quality
caudate nucleus	UBERON:0001873	79.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.53	gold quality
metanephros	UBERON:0000081	78.52	gold quality
Ammon’s horn	UBERON:0001954	78.49	gold quality
sigmoid colon	UBERON:0001159	78.34	gold quality
gluteal muscle	UBERON:0002000	78.21	silver quality
muscle tissue	UBERON:0002385	78.07	gold quality
fundus of stomach	UBERON:0001160	78.06	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	78.04	silver quality
thoracic mammary gland	UBERON:0005200	77.84	gold quality
biceps brachii	UBERON:0001507	77.77	gold quality
mammary gland	UBERON:0001911	77.71	gold quality
renal medulla	UBERON:0000362	77.61	gold quality
multicellular organism	UBERON:0000468	77.59	gold quality
material anatomical entity	UBERON:0000465	77.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.54	gold quality
spinal cord	UBERON:0002240	77.43	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	5133.64
E-GEOD-135922	yes	3760.59
E-MTAB-8410	yes	3014.64
E-MTAB-10662	yes	632.83
E-GEOD-134144	yes	43.37
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Colon	tissue	247.2	medium
Rectum	tissue	162.0	high
Adipose tissue	tissue	77.9	low
Cerebellum	tissue	70.2	not detected
Frontal cortex	tissue	56.6
Epididymis	tissue	48.9	not detected
Lung	tissue	48.0	not detected
Hippocampal formation	tissue	46.8
Tongue	tissue	39.4
Gallbladder	tissue	36.0	high
Cerebral cortex	tissue	35.5	low
Somatosensory cortex	tissue	35.5
Thyroid gland	tissue	35.4	not detected
Seminal vesicle	tissue	34.8	not detected
Kidney	tissue	33.9	low
Occipital cortex	tissue	31.5
Entorhinal cortex	tissue	31.2
Superior colliculi	tissue	29.9
Prefrontal cortex	tissue	29.3
Skeletal muscle	tissue	28.6	not detected
Pancreas	tissue	27.7	low
Motor cortex	tissue	26.0
Heart muscle	tissue	25.5	not detected
Retrosplenial and cingulate cortex	tissue	25.2
Temporal cortex	tissue	25.0
Caudate putamen	tissue	24.9
Breast	tissue	22.0	not detected
Insular cortex	tissue	20.7
Retrosplenial cortex	tissue	20.0
Bone marrow	tissue	18.4	not detected
Hippocampus	tissue	17.2	not detected
Pituitary gland	tissue	15.9
Parathyroid gland	tissue	15.9
Thalamus	tissue	15.2
Pons	tissue	14.1
Amygdala	tissue	13.8
Midbrain	tissue	12.8
Choroid plexus	tissue	10.3
Postcentral gyrus	tissue	10.3
Salivary gland	tissue	9.8	not detected
Placenta	tissue	8.1	not detected
Ovary	tissue	7.7	not detected
Substantia nigra	tissue	7.1
Stomach 1	tissue	6.9	not detected
Spinal cord	tissue	6.7
Medulla oblongata	tissue	6.3
Locus coeruleus	tissue	6.1
Cervix	tissue	6.0	not detected
Nucleus accumbens	tissue	5.9
Vagina	tissue	5.2	not detected
Small intestine	tissue	4.7	not detected
Olfactory bulb	tissue	4.5
Putamen	tissue	4.4
Fallopian tube	tissue	4.4	not detected
Ventral forebrain	tissue	4.0
Hypothalamus	tissue	3.7
Corpus callosum	tissue	3.7
Duodenum	tissue	3.6	not detected
Septum	tissue	3.4
Periaqueductal gray	tissue	3.0

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Flocculonodular lobe (173.8), Cerebellar cortex (157.1), Vermis (134.1), Dorsal hippocampus (46.8), Lingual gyrus (37.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CA4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

9 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-3116	97.07	65.78	1324

Functional genomics

gnomAD constraint: pLI 1.33e-06, LOEUF 0.975, missense Z 0.137 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000300900 — one region, missense o/e 0.99.

Literature-anchored findings (GeneRIF, showing 25)

• binding by extracellular loop 4 of the human AE1 Cl-/HCO3- exchanger (PMID:11994299)
• carbonic anhydrase IV binds EC4 of NBC1, and this interaction is essential for full NBC1 activity (PMID:14567693)
• mutation was found to cosegregate with the retinitis pigmentosa RP17 phenotype in two large families (PMID:15090652)
• CA inhibitors may have long-term adverse effects on vision. (PMID:15563508)
• characterized the CA IV expressed in Capan-1 cells (PMID:17409381)
• A novel mutation has been identified in CA4 that provides further evidence that impaired pH regulation may underlie photoreceptor degeneration in retinitis pigmentosa (PMID:17652713)
• No mutation was found in the coding regions and intron-exon boundaries of the genes for CA II, CA IV, CA XIV, kNCB1, NHE3, NHE8, NHRF1, NHRF2 and SLC26A6 amplified from genomic DNA of family members with pRTA. (PMID:17881426)
• CAIV p.R14W sequence variant found in one of the patients with Bothnia dystrophy phenotype is benign polymorphism in population of northern Sweden. (PMID:18344446)
• Apoptosis induced by the CA IV mutants could be prevented, at least partially, by treating the cells with dorzolamide, a CA inhibitor (PMID:19211803)
• renal injury inflicted by expression of human carbonic anhydrase IV folding mutants was markedly enhanced by haploinsufficiency of the endoplasmic reticulum cochaperone p58(IPK). (PMID:20308551)
• The results suggest that the expression level of carbonic anhydrase IV may be important to maintain retina function in retinitis pigmentosa. (PMID:20450258)
• compared the subcellular localization and post-translational processing of wild-type (WT)- and retinitis pigmentosa 17 mutant-CAIV in three cell types (PMID:20626030)
• data suggest that extracellular membrane-bound CAIV, but not cytosolic CAII, augments transport activity of MCT2 in a non-catalytic manner, possibly by facilitating a proton pathway other than His-88 (PMID:21680735)
• Two SNPs of carbonic anhydrase IV, which are responsible for amino acid changes, were found. The frequencies of these SNPs were not significantly different between the caries-free group and the group with caries (PMID:22021688)
• The generation of CA III and IV autoantibodies, antioxidant enzymes, and cytokines might influence each other. (PMID:23049597)
• membrane-associated CA IV contributes robust catalytic activity intracellularly, and this activity participates in regulating H(+) dynamics in the cytosol (PMID:23297198)
• Although CA IV has been shown to be active in mediating CO2 and HCO3 (-) transport in many important tissues like kidney and lung, and in isolated cells from brain and muscle, the gene for CA IV appears not to be essential. (PMID:24146379)
• Coexpression of CAIV with MCT1 and MCT4 resulted in a significant increase in MCT transport activity. (PMID:24338019)
• Carbonic anhydrase 4 is lost in papillary thyroid carcinoma but not thyroid nodules (PMID:24880201)
• CA4 is a novel tumour suppressor in Colorectal cancer through the inhibition of the Wnt signalling pathway by targeting the WTAP-WT1-TBL1 axis. CA4 methylation may serve as an independent biomarker for the recurrence of Colorectal cancer . (PMID:26071132)
• This study analyzed the direct interaction between CAIV and the two Monocarboxylate transporters (MCTs) chaperones basigin (CD147) and embigin (GP70). In human CD147, binding of CAIV was mediated by the negatively charged Glu-73. (PMID:30446621)
• highest susceptibility effect was noticed in the rs2274328 of carbonic anhydrase VI (AA vs CC) model (d = 0.18; 95% CI (confidence interval): -1.77, 2.13), but this effect was not significant [meta-analysis] (PMID:31895503)
• carbonic anhydrase 1 (CA1) and CA4 were identified as potential biomarkers of Colon adenocarcinoma due to their predictive roles in diagnosis and prognosis, and the results were further confirmed by a series of analyses. (PMID:32031891)
• Enhanced carbonic anhydrase expression with calcification and fibrosis in bronchial cartilage during COPD. (PMID:34954529)
• Carbonic Anhydrase 4 Serves as A Novel Prognostic Biomarker and Therapeutic Target for Non-Small Cell Lung Cancer: A Study Based on TCGA Samples. (PMID:36944625)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	ca4c	ENSDARG00000044512
mus_musculus	Car4	ENSMUSG00000000805
rattus_norvegicus	Ca4	ENSRNOG00000002916
drosophila_melanogaster	CAH13	FBGN0033542
drosophila_melanogaster	CAH14	FBGN0034554
drosophila_melanogaster	CAH15	FBGN0034560
drosophila_melanogaster	CAH7	FBGN0037788
drosophila_melanogaster	CAH4	FBGN0039235
drosophila_melanogaster	CARPB	FBGN0052698
caenorhabditis_elegans		WBGENE00000279
caenorhabditis_elegans		WBGENE00000283
caenorhabditis_elegans	cah-6	WBGENE00000284

Paralogs (14): CA11 (ENSG00000063180), CA12 (ENSG00000074410), CA2 (ENSG00000104267), CA9 (ENSG00000107159), CA14 (ENSG00000118298), CA6 (ENSG00000131686), CA1 (ENSG00000133742), CA10 (ENSG00000154975), CA3 (ENSG00000164879), CA7 (ENSG00000168748), CA5B (ENSG00000169239), CA5A (ENSG00000174990), CA8 (ENSG00000178538), CA13 (ENSG00000185015)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1096574) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
postnatal lethality	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P00921	100.0%	Diamond
Macaca mulatta	P00916	99.2%	Diamond
Macaca nemestrina	P35217	99.2%	Diamond
Pan troglodytes	Q7M317	99.2%	Diamond
Pinctada fucata	A0ZSF2	98.8%	Diamond
Pinctada maxima	A0ZSF3	98.5%	Diamond
Gorilla gorilla gorilla	Q7M316	98.1%	Diamond
Sus scrofa	Q5S1S4	93.1%	Diamond
Ovis aries	P00922	92.3%	Diamond
Chlamydomonas reinhardtii	P20507	92.1%	Diamond
Equus caballus	P07450	91.9%	Diamond
Oryctolagus cuniculus	P00919	85.7%	Diamond
Chionodraco hamatus	P83299	77.6%	Diamond
Pseudaspius hakonensis	Q8UWA5	76.0%	Diamond
Canis lupus familiaris	Q865C0	75.2%	Diamond
Monodelphis domestica	Q8HY33	72.4%	Diamond
Gallus gallus	P07630	70.8%	Diamond
Arabidopsis thaliana	Q9FM99	68.0%	Diamond
Nicotiana langsdorffii x Nicotiana sanderae	Q84UV8	53.4%	Diamond
Klebsiella pneumoniae	O52535	46.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SCARNA20	ncRNA	677681
USP32	protein-coding	84669
HEATR6-DT	ncRNA	105371849
HEATR6	protein-coding	63897
CHCT1	protein-coding	124773

Protein

Protein identifiers

Carbonic anhydrase 4 — P22748 (reviewed: P22748)

Alternative names: Carbonate dehydratase IV, Carbonic anhydrase IV

All UniProt accessions (4): P22748, K7EIH9, K7EKY5, K7ENI8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.

Subunit / interactions. Interacts with SLC4A4.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the endothelium of the choriocapillaris in eyes (at protein level). Not expressed in the retinal epithelium at detectable levels.

Disease relevance. Retinitis pigmentosa 17 (RP17) [MIM:600852] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry. Defective acid overload removal from retina and retinal epithelium, due to mutant CA4, is responsible for photoreceptor degeneration, indicating that impaired pH homeostasis is the most likely cause underlying the RP17 phenotype.

Activity regulation. Activated by histamine, L-adrenaline, D-phenylalanine, L- and D-histidine. Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide and Foscarnet (phosphonoformate trisodium salt).

Similarity. Belongs to the alpha-carbonic anhydrase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P22748-1	1	yes
P22748-2	2

RefSeq proteins (1): NP_000708* (*=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
IPR041874	CA4/CA15	Family

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)

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

UniProt features (51 total): strand 16, helix 11, sequence variant 6, binding site 4, disulfide bond 2, splice variant 2, turn 2, signal peptide 1, chain 1, propeptide 1, mutagenesis site 1, sequence conflict 1, domain 1, active site 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

10 structures by resolution:

PDB	Title	Method	Resolution (Å)
3FW3	Crystal Structure of soluble domain of CA4 in complex with Dorzolamide	X-RAY DIFFRACTION	1.72
5KU6	Crystal structure for the complex of human carbonic anhydrase IV and methazolamide	X-RAY DIFFRACTION	1.8
5JN8	Crystal Structure for the complex of human carbonic anhydrase IV and acetazolamide	X-RAY DIFFRACTION	1.85
3F7U	Crystal Structure of soluble domain of CA4 in complex with small molecule.	X-RAY DIFFRACTION	2
5JNA	Crystal structure for the complex of human carbonic anhydrase IV and topiramate	X-RAY DIFFRACTION	2
5JNC	Crystal structure for the complex of human carbonic anhydrase IV and 4-aminomethylbenzene …	X-RAY DIFFRACTION	2
3F7B	Crystal Structure of soluble domain of CA4 in complex with small molecule.	X-RAY DIFFRACTION	2.05
5IPZ	Crystal structure of human carbonic anhydrase isozyme IV with …	X-RAY DIFFRACTION	2.1
5JN9	Crystal structure for the complex of human carbonic anhydrase IV and ethoxyzolamide	X-RAY DIFFRACTION	2.1
1ZNC	HUMAN CARBONIC ANHYDRASE IV	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22748-F1	89.86	0.81

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Lyases, Metabolic proteins, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Eye disease

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; vesicles

Antibody reliability (HPA): IH enhanced · IF uncertain

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)

Position	Role
88	proton donor/acceptor

Ligand- & substrate-binding residues (4)

Position	Role
115	Zn(2+)
117	Zn(2+)
140	Zn(2+)
225–226	substrate

Post-translational modifications (1)

Type	Positions
Gpi-anchor amidated serine	284

Disulfide bonds (2)

Type	Positions
Disulfide bond	24–36, 46–229

Mutagenesis-validated functional residues (1)

Position	Phenotype
284	loss of c-terminal domain removal and abolishes carbonate dehydratase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-1237044	Erythrocytes take up carbon dioxide and release oxygen	curated
R-HSA-1247673	Erythrocytes take up oxygen and release carbon dioxide	curated
R-HSA-1475029	Reversible hydration of carbon dioxide	curated
R-HSA-1430728	Metabolism	—
R-HSA-1480926	O2/CO2 exchange in erythrocytes	—
R-HSA-382551	Transport of small molecules	—

MSigDB gene sets: 246 (showing top): GOMF_CARBONATE_DEHYDRATASE_ACTIVITY, NKX25_02, GOCC_SECRETORY_GRANULE, MODULE_45, GOCC_CELL_SURFACE, MARTINEZ_RB1_TARGETS_UP, GOCC_TRANS_GOLGI_NETWORK, DELYS_THYROID_CANCER_DN, RYTAAWNNNTGAY_UNKNOWN, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_BICARBONATE_TRANSPORT, HP1SITEFACTOR_Q6, SANSOM_APC_TARGETS_DN, MODULE_88, GOCC_APICAL_PLASMA_MEMBRANE

GO Biological Process (1): bicarbonate transport (GO:0015701)

GO Molecular Function (5): carbonate dehydratase activity (GO:0004089), zinc ion binding (GO:0008270), protein binding (GO:0005515), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (15): rough endoplasmic reticulum (GO:0005791), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), apical plasma membrane (GO:0016324), transport vesicle membrane (GO:0030658), secretory granule membrane (GO:0030667), brush border membrane (GO:0031526), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), side of membrane (GO:0098552)

Reactome top-level categories

3 top-level categories:

Category	Pathways
O2/CO2 exchange in erythrocytes	2
Metabolism	1
Transport of small molecules	1

GO top-level categories

28 GO namespaces:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
intracellular membrane-bounded organelle	2
membrane	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
transport	1
hydro-lyase activity	1
transition metal ion binding	1
binding	1
catalytic activity	1
cation binding	1
endoplasmic reticulum	1
endomembrane system	1
Golgi apparatus subcompartment	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
apical part of cell	1
plasma membrane region	1
transport vesicle	1
secretory granule	1
brush border	1
apical plasma membrane	1
cell projection membrane	1
extracellular vesicle	1
leaflet of membrane bilayer	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 14 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

14 experimentally-supported GO terms:

GO term	NS	Evidence
bicarbonate transport	BP	mutant phenotype
Golgi apparatus	CC	direct assay
apical plasma membrane	CC	direct assay
brush border membrane	CC	direct assay
cell surface	CC	direct assay
endoplasmic reticulum-Golgi intermediate compartment	CC	direct assay
external side of plasma membrane	CC	direct assay
extracellular exosome	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
plasma membrane	CC	direct assay
rough endoplasmic reticulum	CC	direct assay
secretory granule membrane	CC	direct assay
trans-Golgi network	CC	direct assay
transport vesicle membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,884 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CA4	CYP24A1	Q07973	717
CA4	PRSS12	P56730	717
CA4	PKD2L1	Q9P0L9	703
CA4	FSCN2	O14926	697
CA4	RP9	Q8TA86	696
CA4	TALDO1	P37837	673
CA4	PRPF31	Q8WWY3	661
CA4	PRPF3	O43395	652
CA4	IMPDH1	P20839	641
CA4	PRPF8	Q6P2Q9	624
CA4	TOPORS	Q9NS56	618
CA4	CERKL	Q49MI3	617
CA4	GUCA1B	Q9UMX6	606
CA4	RDH12	Q96NR8	590
CA4	ZNF513	Q8N8E2	588

IntAct

Human interaction partners of CA4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
SLC4A4	colocalization	0.460	2
ALDH1A2	physical association	0.400	1
CDK18	physical association	0.400	1
PIH1D1	physical association	0.370	1
PRDX2	physical association	0.370	1
CDK6	association	0.350	1

BioGRID (16 interactions; top human partners by supporting records): WTAP (Affinity Capture-MS; 3 records), CDK18 (Affinity Capture-MS; 2 records), SLC4A1 (Co-fractionation; 2 records), ALDH1A2 (Affinity Capture-MS), CDK6 (Affinity Capture-MS), NF1 (Negative Genetic), PARP16 (Proximity Label-MS), PIH1D1 (Two-hybrid), PRDX2 (Two-hybrid), SPPL3 (Positive Genetic), TEX101 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for CA4: 374 ClinVar records (16 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	10
Uncertain significance	190
Likely benign	119
Benign	7

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 16 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1519203	NM_000717.5(CA4):c.102C>A (p.Tyr34Ter)	Pathogenic	criteria provided, single submitter	1
2095265	NM_000717.5(CA4):c.58G>T (p.Glu20Ter)	Pathogenic	criteria provided, single submitter	1
3689423	NM_000717.5(CA4):c.138C>A (p.Cys46Ter)	Pathogenic	criteria provided, single submitter	1
3699233	NM_000717.5(CA4):c.250C>T (p.Gln84Ter)	Pathogenic	criteria provided, single submitter	1
808304	NM_000717.5(CA4):c.368del (p.Tyr123fs)	Likely pathogenic	criteria provided, single submitter	1
1024689	NM_000717.5(CA4):c.656G>A (p.Arg219His)	Likely pathogenic	criteria provided, single submitter	1
1360011	NM_000717.5(CA4):c.415-2_416del	Likely pathogenic	criteria provided, single submitter	1
1479585	NM_000717.5(CA4):c.112+1G>A	Likely pathogenic	criteria provided, single submitter	1
1910917	NM_000717.5(CA4):c.113-2A>C	Likely pathogenic	criteria provided, single submitter	1
2056863	NM_000717.5(CA4):c.268+1G>A	Likely pathogenic	criteria provided, single submitter	1
2127685	NM_000717.5(CA4):c.415-1G>A	Likely pathogenic	criteria provided, single submitter	1
2193862	NM_000717.5(CA4):c.513+1G>T	Likely pathogenic	criteria provided, single submitter	1
3028475	NM_000717.5(CA4):c.687C>A (p.Cys229Ter)	Likely pathogenic	criteria provided, single submitter	1
3028479	NM_000717.5(CA4):c.937T>C (p.Ter313Arg)	Likely pathogenic	criteria provided, single submitter	1
1444632	NC_000017.10:g.(?58230965)(58235066_?)del	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CA4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 742):

Position(s)	Effect	Δscore	Sites
17:60150093–60150094	donor_loss	1.0000	5
17:60156674	donor_gain	1.0000
17:60157573–60157574	donor_loss	1.0000	5
17:60158059–60158060	acceptor_loss	1.0000	5
17:60158128–60158129	donor_loss	1.0000	5
17:60158277	acceptor_gain	1.0000
17:60158282	acceptor_loss	1.0000	3
17:60158447–60158448	donor_loss	1.0000	5
17:60153676	donor_gain	0.9900
17:60156553	acceptor_gain	0.9900

AlphaMissense

542 missense substitutions predicted likely pathogenic (of 2,026 scored), across 132 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H117	8	0.969	0.994
N85	8	0.959	0.989
H128	8	0.959	0.988
H115	8	0.952	0.986
H140	8	0.952	0.974
F238	8	0.919	0.985
H143	8	0.903	0.966
F252	8	0.901	0.985
W235	7	0.979	0.992
C229	7	0.978	0.991
W118	7	0.976	0.994
C46	7	0.967	0.986
E138	7	0.966	0.983
E127	7	0.964	0.991
W42	7	0.963	0.996
R271	7	0.961	0.995
C24	7	0.939	0.973
C36	7	0.928	0.973
F218	7	0.923	0.984
W23	7	0.917	0.987

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Rectum Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	8.52e-07
Breast Invasive Carcinoma (validation)	favorable	0.000195
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000235

Disease associations

OMIM: gene MIM:114760 | disease phenotypes:

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
retinitis pigmentosa 17	Strong	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant	2

Mondo (3): inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa 17 (MONDO:0010945), retinitis pigmentosa (MONDO:0019200)

Orphanet (1): OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

31 phenotypes (HPO-id order):

HPO	Term
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract
HP:0007843	Attenuation of retinal blood vessels
HP:0007994	Peripheral visual field loss
HP:0008046	Abnormal retinal vascular morphology
HP:0011505	Cystoid macular edema
HP:0012426	Optic disc drusen
HP:0030466	Abnormal full-field electroretinogram
HP:0030488	Abnormal central response of multifocal electroretinogram
HP:0030610	Photoreceptor outer segment loss on macular OCT
HP:0030786	Photopsia

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C563437	Retinitis Pigmentosa 17 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095180 (PROTEIN FAMILY), CHEMBL3729 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CA4 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

4 curated-mechanism drugs:

Drug	Modality	Max phase
ACETAZOLAMIDE	Small molecule	4
DICHLORPHENAMIDE	Small molecule	4
METHAZOLAMIDE	Small molecule	4
TOPIRAMATE	Small molecule	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,363,103 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

59 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL20	ACETAZOLAMIDE	4	29,000
CHEMBL17	DICHLORPHENAMIDE	4	9,090
CHEMBL19	METHAZOLAMIDE	4	67
CHEMBL220492	TOPIRAMATE	4	35,499
CHEMBL112	ACETAMINOPHEN	4	159,007
CHEMBL325041	BORTEZOMIB	4	13,415
CHEMBL220491	BRINZOLAMIDE	4	8,467
CHEMBL118	CELECOXIB	4	113,751
CHEMBL1055	CHLORTHALIDONE	4	20,585
CHEMBL6466	COUMARIN	4	204,529
CHEMBL926	DOBUTAMINE	4	17,217
CHEMBL218490	DORZOLAMIDE	4	10,341
CHEMBL18	ETHOXZOLAMIDE	4	3,064
CHEMBL902	FAMOTIDINE	4	67,399
CHEMBL35	FUROSEMIDE	4	224,391
CHEMBL537	HYDROQUINONE	4	297,955
CHEMBL941	IMATINIB	4	113,105
CHEMBL406	INDAPAMIDE	4	16,245
CHEMBL58323	LACOSAMIDE	4	5,800
CHEMBL1286	LEVETIRACETAM	4	14,176
CHEMBL419	MAFENIDE	4
CHEMBL255863	NILOTINIB	4
CHEMBL14060	PHENOL	4
CHEMBL1200731	POTASSIUM CHLORIDE	4
CHEMBL1141	POTASSIUM IODIDE	4
CHEMBL1200471	PYRITHIONE ZINC	4
CHEMBL424	SALICYLIC ACID	4
CHEMBL1356	SODIUM BENZOATE	4
CHEMBL1355	SODIUM CITRATE	4
CHEMBL1060	SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4
CHEMBL21	SULFANILAMIDE	4
CHEMBL1054	TRICHLORMETHIAZIDE	4
CHEMBL609	TRIENTINE	4
CHEMBL865	VALDECOXIB	4
CHEMBL2105581	VERALIPRIDE	4
CHEMBL750	ZONISAMIDE	4
CHEMBL145	CAFFEIC ACID	3
CHEMBL140	CURCUMIN	3
CHEMBL1362	FLUORIDE ION	3
CHEMBL50	QUERCETIN	3
CHEMBL165	RESVERATROL	3
CHEMBL310671	SACCHARIN	3
CHEMBL19612	SPERMIDINE	3
CHEMBL508338	THIMEROSAL	3
CHEMBL251680	COUMAPHOS	2
CHEMBL8145	DAIDZEIN	2
CHEMBL107217	DITIOCARB SODIUM	2
CHEMBL6246	ELLAGIC ACID	2
CHEMBL288114	GALLIC ACID	2
CHEMBL286738	IROSUSTAT	2
CHEMBL250450	ISOQUERCETIN	2
CHEMBL151	LUTEOLIN	2
CHEMBL4297315	PCI-27483	2
CHEMBL1288786	PROPAZOLAMIDE	2
CHEMBL181886	PYRUVATE SODIUM	2
CHEMBL69759	SONEPIPRAZOLE	2
CHEMBL2107036	SULFASUCCINAMIDE	2
CHEMBL457077	SALVIANOLIC ACID A	1
CHEMBL1615281	SLC-0111	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Carbonic anhydrases

Most potent curated ligand interactions (8 total), top 8:

Ligand	Action	Affinity	Parameter
methazolamide	Inhibition	7.62	pKi
acetazolamide	Inhibition	7.6	pKi
topiramate	Inhibition	7.37	pKi
salvianolic acid A	Inhibition	7.17	pKi
chlorthalidone	Inhibition	6.71	pKi
compound 5b [PMID: 31287314]	Inhibition	6.03	pKi
compound 5a [PMID: 31287314]	Inhibition	5.0	pKi
diclofenamide	Inhibition	4.82	pKi

Binding affinities (BindingDB)

1624 measured of 1835 human assays (1940 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4577993	KD	0.14 nM
CHEMBL4560953	KD	0.15 nM
CHEMBL4553790	KD	0.15 nM
CHEMBL4516072	KD	0.19 nM
4-Nitro-benzenesulfonamide	KI	0.2 nM
CHEMBL2333417	KD	0.2 nM
CHEMBL4441652	KD	0.22 nM
CHEMBL4567916	KD	0.23 nM
CHEMBL4462447	KD	0.23 nM
CHEMBL4448119	KD	0.24 nM
CHEMBL4587295	KD	0.25 nM
p-Halide-sulfanilamide derivative, 2	KI	0.3 nM
CHEMBL4558235	KD	0.3 nM
CHEMBL4474833	KD	0.34 nM
CHEMBL4474251	KD	0.37 nM
CHEMBL4443078	KD	0.38 nM
CHEMBL4558457	KD	0.38 nM
CHEMBL4555622	KD	0.39 nM
CHEMBL4160627	KD	0.41 nM
CHEMBL4449149	KD	0.45 nM
CHEMBL4567746	KD	0.58 nM
CHEMBL4439634	KD	0.58 nM
2-(3-hydroxyphenyl)-1,1-dioxo-3-[(prop-2-yn-1-ylamino)methyl]-2H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide hydrochloride	IC50	0.6 nM
CHEMBL4475315	KD	0.64 nM
CHEMBL4463683	KD	0.64 nM
CHEMBL4442511	KD	0.76 nM
CHEMBL4473602	KD	0.77 nM
CHEMBL4573916	KD	0.77 nM
Compound 17g1	IC50	0.79 nM
Compound 5b	IC50	0.82 nM
CHEMBL4441730	KD	0.83 nM
3-(morpholin-4-ylmethyl)-1,1-dioxo-2-(prop-2-en-1-yl)-2H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide	IC50	0.99 nM
Compound 17m1	IC50	1.05 nM
CHEMBL4543024	KD	1.1 nM
Compound 17a7	IC50	1.11 nM
2-(3-hydroxyphenyl)-3-(morpholin-4-ylmethyl)-1,1-dioxo-2H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide	IC50	1.15 nM
2-(3-Methoxyphenyl)-3-[(4-morpholinyl)methyl]-2H-thieno-[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide	IC50	1.27 nM
(4R)-4-amino-2-(3-methoxypropyl)-1,1-dioxo-2H,3H,4H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide	IC50	1.28 nM
2-N-(4-amino-3-chloro-5-fluorobenzene)-1,3,4-thiadiazole-2,5-disulfonamide	KI	1.4 nM
Compound 17n1	IC50	1.5 nM
CHEMBL4570253	KD	1.5 nM
CHEMBL4453207	KI	1.5 nM
2-methyl-3-(morpholin-4-ylmethyl)-1,1-dioxo-2H-1,7,2-thieno[3,2-e][1,2]thiazine-6-sulfonamide hydrochloride	IC50	1.66 nM
CHEMBL4578934	KD	1.7 nM
CHEMBL4590754	KD	1.9 nM
CHEMBL4593434	KD	2 nM
Compound 17j1	IC50	2.01 nM
WB-4101 hydrochloride	KI	2.09 nM
5-(Aminosulfonyl)-2-[(3,4-difluorophenyl)thio]-N-(4-methoxybenzyl)nicotinamide	IC50	2.19 nM
2-[2-(Propylamino)ethyl]-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide hydrochloride	IC50	2.25 nM

ChEMBL bioactivities

1932 potent at pChembl≥5 of 2056 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Kd	0.01	nM	CHEMBL4569008
11.00	Kd	0.01	nM	CHEMBL4451500
11.00	Kd	0.01	nM	CHEMBL4584546
10.70	Kd	0.02	nM	CHEMBL4572161
10.70	Kd	0.02	nM	CHEMBL4562296
10.52	Kd	0.03	nM	CHEMBL4450545
10.52	Kd	0.03	nM	CHEMBL4173471
10.52	Kd	0.03	nM	CHEMBL4450456
10.52	Kd	0.03	nM	CHEMBL4593681
10.49	Kd	0.032	nM	CHEMBL4173471
10.40	Kd	0.04	nM	CHEMBL4166964
10.40	Kd	0.04	nM	CHEMBL4436290
10.30	Kd	0.05	nM	CHEMBL4166964
10.22	Kd	0.06	nM	CHEMBL4565224
10.22	Kd	0.06	nM	CHEMBL4468834
10.22	Kd	0.06	nM	CHEMBL4521683
10.21	Kd	0.062	nM	CHEMBL4441730
10.05	Kd	0.089	nM	CHEMBL4553790
10.05	Kd	0.09	nM	CHEMBL4165570
10.03	Kd	0.093	nM	CHEMBL4449149
10.00	Kd	0.099	nM	CHEMBL4165570
10.00	Kd	0.1	nM	CHEMBL4558235
9.96	Kd	0.11	nM	CHEMBL4456084
9.96	Kd	0.11	nM	CHEMBL4475073
9.96	Kd	0.11	nM	CHEMBL4446052
9.92	Kd	0.12	nM	CHEMBL4475315
9.89	Kd	0.13	nM	CHEMBL4452277
9.85	Kd	0.14	nM	CHEMBL4218335
9.82	Kd	0.15	nM	CHEMBL4573894
9.82	Kd	0.15	nM	CHEMBL4592616
9.80	Kd	0.16	nM	CHEMBL4576689
9.77	Kd	0.17	nM	CHEMBL4555622
9.77	Kd	0.17	nM	CHEMBL4456851
9.77	Kd	0.17	nM	CHEMBL4539233
9.77	Kd	0.17	nM	CHEMBL4468310
9.77	Kd	0.17	nM	CHEMBL4166643
9.77	Kd	0.17	nM	CHEMBL4445515
9.74	Kd	0.18	nM	CHEMBL4166643
9.74	Kd	0.18	nM	CHEMBL4458989
9.74	Kd	0.18	nM	CHEMBL4573916
9.74	Kd	0.18	nM	CHEMBL4462447
9.74	Kd	0.18	nM	CHEMBL4578934
9.72	Kd	0.19	nM	CHEMBL4516072
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
9.66	Kd	0.22	nM	CHEMBL4560953
9.66	Kd	0.22	nM	CHEMBL4474251
9.66	Ki	0.22	nM	CHEMBL4577408

PubChem BioAssay actives

2032 with measured affinity, of 2827 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
4-chloro-N-(3-hydroxypropyl)-2-phenylsulfanyl-5-sulfamoylbenzamide	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2,4-dichloro-N-(3-hydroxypropyl)-5-sulfamoylbenzamide	1361384: Binding affinity to recombinant human carbonic anhydrase 4 (19 to 284 residues) expressed in mammalian expression system 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
2,4-dichloro-N-(2-methoxyethyl)-5-sulfamoylbenzamide	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	<0.0001	uM
N-benzyl-2,4-dichloro-5-sulfamoylbenzamide	1361384: Binding affinity to recombinant human carbonic anhydrase 4 (19 to 284 residues) expressed in mammalian expression system assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	0.0001	uM
4-bromo-N-butyl-2-cyclohexylsulfanyl-5-sulfamoylbenzamide	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 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	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0001	uM
4-chloro-N-cyclohexyl-2-phenylsulfanyl-5-sulfamoylbenzamide	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0001	uM
N-(benzimidazol-1-yl)-4-chloro-2-phenylsulfanyl-5-sulfamoylbenzamide	1373179: Binding affinity to recombinant human N-terminal His6-tagged carbonic anhydrase 4 expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assay	kd	0.0001	uM
1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-N-[(E)-(4-methoxyphenyl)methylideneamino]-5-oxopyrrolidine-3-carboxamide	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0001	uM
N-(3,5-dimethylpyrazol-1-yl)-1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxamide	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0001	uM
1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxylic acid	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0001	uM
2-benzylsulfanyl-4-chloro-5-sulfamoylbenzamide	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0001	uM
N-[(E)-(4-bromophenyl)methylideneamino]-1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxamide	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0001	uM
1-(2-bromophenyl)-5-oxo-N-(4-sulfamoylphenyl)pyrrolidine-3-carboxamide	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0001	uM
1-(3,5-dimethyl-4-sulfamoylphenyl)-N-[(E)-(4-methoxyphenyl)methylideneamino]-5-oxopyrrolidine-3-carboxamide	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0001	uM
2-benzylsulfanyl-4-bromo-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0002	uM
4-bromo-2-cyclohexylsulfanyl-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0002	uM
2-(benzenesulfinyl)-4-bromo-N-(2-hydroxyethyl)-5-sulfamoylbenzamide	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0002	uM
2-(benzenesulfonyl)-4-bromo-N-butyl-5-sulfamoylbenzamide	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0002	uM
N-benzyl-4-chloro-2-cyclohexylsulfanyl-5-sulfamoylbenzamide	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0002	uM
2,4-dibromo-N-butyl-5-sulfamoylbenzamide	1361384: Binding affinity to recombinant human carbonic anhydrase 4 (19 to 284 residues) expressed in mammalian expression system assessed as intrinsic Kd in presence of ANS by fluorescent thermal shift assay	kd	0.0002	uM
4-[1-[(2R)-1-(3-azabicyclo[3.2.2]nonan-3-yl)-3-methyl-1-oxobutan-2-yl]triazol-4-yl]benzenesulfonamide	1557414: Inhibition of carbonic anhydrase (unknown origin)	ki	0.0002	uM
4-[(2-benzylsulfanyl-4-chloro-5-sulfamoylbenzoyl)amino]butanoic acid	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0002	uM
4-chloro-2-(2-phenylethylsulfanyl)-5-sulfamoylbenzamide	1520082: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay	kd	0.0002	uM
3-chloro-4-[4-(hydrazinecarbonyl)-2-oxopyrrolidin-1-yl]-2,6-dimethylbenzenesulfonamide	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0002	uM
1-(3-bromophenyl)-5-oxo-N-(4-sulfamoylphenyl)pyrrolidine-3-carboxamide	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0002	uM
N-[(E)-benzylideneamino]-5-oxo-1-(4-sulfamoylphenyl)pyrrolidine-3-carboxamide	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0002	uM
N-[(E)-benzylideneamino]-1-(3,5-dimethyl-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxamide	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0002	uM
(2R)-3-phenyl-2-[4-(4-sulfamoylphenyl)triazol-1-yl]-N-(2-thiophen-3-ylethyl)propanamide	1557414: Inhibition of carbonic anhydrase (unknown origin)	ki	0.0002	uM
1-(2-chloro-3,5-dimethyl-4-sulfamoylphenyl)-N-[(E)-(4-nitrophenyl)methylideneamino]-5-oxopyrrolidine-3-carboxamide	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0002	uM
1-(3,5-dimethyl-4-sulfamoylphenyl)-N-[(E)-(4-nitrophenyl)methylideneamino]-5-oxopyrrolidine-3-carboxamide	1515317: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay	kd	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	6
trichostatin A	decreases expression, affects cotreatment	3
mercuric bromide	decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
sulfamic acid	decreases activity	1
oryzalin	decreases activity, affects binding	1
butyraldehyde	increases expression	1
chloric acid	decreases activity	1
sodium metasilicate	decreases activity	1
potassium periodate	decreases activity	1
molybdate	decreases activity	1
tungstate	decreases activity	1
pentanal	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
belinostat	decreases expression	1
abrine	increases expression	1
quinocetone	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Acetazolamide	affects binding, decreases activity	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Amphotericin B	decreases expression	1

ChEMBL screening assays

202 unique, capped per target: 195 binding, 6 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*
CHEMBL4187334	ADMET	Binding affinity to recombinant human N-terminal His6-tagged carbonic anhydrase 4 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*
CHEMBL863243	Functional	Activation constant against recombinant human CA IV isozyme by the esterase method	Carbonic anhydrase activators: X-ray crystal structure of the adduct of human isozyme II with L-histidine as a platform for the design of stronger activators. — *Bioorg Med Chem Lett*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 238 trials:

NCT	Phase	Status	Title
NCT00717080	Phase 4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	Phase 3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	Phase 3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	Phase 3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	Phase 3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	Phase 3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	Phase 3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	Phase 3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	Phase 3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	Phase 3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	Phase 3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	Phase 3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	Phase 3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT07710196	Phase 3	NOT_YET_RECRUITING	A 24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	Phase 2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	Phase 2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	Phase 2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	Phase 2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	Phase 2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	Phase 2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	Phase 2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	Phase 2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	Phase 2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	Phase 2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	Phase 2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	Phase 2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	Phase 2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	Phase 2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	Phase 2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	Phase 2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	Phase 2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	Phase 2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	Phase 2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	Phase 2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	Phase 2	ACTIVE_NOT_RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	Phase 2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	Phase 2	ACTIVE_NOT_RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT07796646	Phase 2	NOT_YET_RECRUITING	Study to Evaluate the Long-Term Safety of Ultevursen in Participants With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT00063765	Phase 1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	Phase 1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	Phase 1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa
NCT01068561	Phase 1	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT01482195	Phase 1	COMPLETED	Trial of Subretinal Injection of (rAAV2-VMD2-hMERTK)
NCT01531348	Phase 1	COMPLETED	Intravitreal Injection of MSCs in Retinitis Pigmentosa
NCT01543906	Phase 1	COMPLETED	Oral QLT091001 in Retinitis Pigmentosa (RP) Subjects With an Autosomal Dominant Mutation in Retinal Pigment Epithelial 65 Protein (RPE65)
NCT01604356	Phase 1	COMPLETED	Acupuncture for the Treatment of Vision Loss Due to Retinitis Pigmentosa
NCT01736059	Phase 1	ACTIVE_NOT_RECRUITING	Clinical Trial of Autologous Intravitreal Bone-marrow CD34+ Stem Cells for Retinopathy
NCT02280135	Phase 1	COMPLETED	Clinical Trial of Intravitreal Injection of Autologous Bone Marrow Stem Cells in Patients With Retinitis Pigmentosa
NCT03063021	Phase 1	COMPLETED	The FIGHT-RP1 Study
NCT03772938	Phase 1	UNKNOWN	Stem Cells Therapy in Degenerative Diseases of the Retina
NCT03944239	Phase 1	ACTIVE_NOT_RECRUITING	Safety and Efficacy of Subretinal Transplantation of Clinical Human Embryonic Stem Cell Derived Retinal Pigment Epitheliums in Treatment of Retinitis Pigmentosa
NCT03999021	Phase 1	ACTIVE_NOT_RECRUITING	FIGHT-RP 1 Extension Study
NCT04284293	Phase 1	ACTIVE_NOT_RECRUITING	CNS10-NPC for the Treatment of RP
NCT04925687	Phase 1	COMPLETED	Phase 1 Study of Intravitreal Autologous CD34+ Stem Cell Therapy for Retinitis Pigmentosa
NCT05147701	Phase 1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT06291935	Phase 1	RECRUITING	Safety and Tolerability of Intravitreal Administration of VG901 in Patients With Retinitis Pigmentosa Due to Mutations in the CNGA1 Gene
NCT06319872	Phase 1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06460844	Phase 1	ACTIVE_NOT_RECRUITING	Study to Evaluate Safety of RTx-015 Injection in Retinitis Pigmentosa or Choroideremia Patients (ENVISION)
NCT06936787	Phase 1	RECRUITING	An Open-label, Dose-ascending Study of IGT001 for Retinitis Pigmentosa
NCT07774975	Phase 1	NOT_YET_RECRUITING	Safety Evaluation Study of Pitavastatin PLGA Nano-particle for Retinitis Pigmentosa

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CA4 across ~30M SureChEMBL compounds — explore on Sugi Predict.