KCNN4

Summary

KCNN4 (potassium calcium-activated channel subfamily N member 4, HGNC:6293) is a protein-coding gene on chromosome 19q13.31, encoding Intermediate conductance calcium-activated potassium channel protein 4 (O15554). Intermediate conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with calmodulin which binds the intracellular calcium allowing its opening.

The protein encoded by this gene is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization, which promotes calcium influx. The encoded protein may be part of the predominant calcium-activated potassium channel in T-lymphocytes. This gene is similar to other KCNN family potassium channel genes, but it differs enough to possibly be considered as part of a new subfamily.

Source: NCBI Gene 3783 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dehydrated hereditary stomatocytosis 2 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 26
• Clinical variants (ClinVar): 258 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 73
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002250

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6293
Approved symbol	KCNN4
Name	potassium calcium-activated channel subfamily N member 4
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Aliases	KCa3.1, hSK4, hKCa4, hIKCa1, IK
Ensembl gene	ENSG00000104783
Ensembl biotype	protein_coding
OMIM	602754
Entrez	3783

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000597184, ENST00000598836, ENST00000599107, ENST00000599720, ENST00000600408, ENST00000600909, ENST00000601549, ENST00000648053, ENST00000648319, ENST00000852944, ENST00000852945, ENST00000852946, ENST00000969511, ENST00000969512, ENST00000969513

RefSeq mRNA: 1 — MANE Select: NM_002250 NM_002250

CCDS: CCDS12630

Canonical transcript exons

ENST00000648319 — 9 exons

Exon	Start	End
ENSE00000710931	43772000	43772135
ENSE00000710933	43774192	43774619
ENSE00001355606	43766533	43767089
ENSE00002533195	43776541	43776636
ENSE00003517588	43769442	43769560
ENSE00003560727	43767540	43767707
ENSE00003600564	43769719	43769829
ENSE00003676513	43768963	43769032
ENSE00003838655	43780703	43780973

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 94.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.3425 / max 340.5101, expressed in 1131 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181355	8.8171	991
181356	2.1618	662
181357	1.1000	505
181358	0.2636	142

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	94.43	gold quality
parotid gland	UBERON:0001831	94.32	gold quality
saliva-secreting gland	UBERON:0001044	94.17	gold quality
minor salivary gland	UBERON:0001830	93.66	gold quality
mucosa of transverse colon	UBERON:0004991	91.58	gold quality
granulocyte	CL:0000094	90.83	gold quality
skin of leg	UBERON:0001511	90.05	gold quality
trachea	UBERON:0003126	89.89	gold quality
mouth mucosa	UBERON:0003729	89.44	gold quality
skin of abdomen	UBERON:0001416	87.87	gold quality
nasal cavity mucosa	UBERON:0001826	87.85	gold quality
placenta	UBERON:0001987	87.21	gold quality
lymph node	UBERON:0000029	86.56	gold quality
transverse colon	UBERON:0001157	86.45	gold quality
rectum	UBERON:0001052	85.98	gold quality
zone of skin	UBERON:0000014	85.91	gold quality
vermiform appendix	UBERON:0001154	85.82	gold quality
spleen	UBERON:0002106	85.57	gold quality
right uterine tube	UBERON:0001302	84.75	gold quality
tonsil	UBERON:0002372	84.62	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.56	gold quality
monocyte	CL:0000576	84.26	gold quality
prostate gland	UBERON:0002367	84.21	gold quality
leukocyte	CL:0000738	84.17	gold quality
mononuclear cell	CL:0000842	84.07	gold quality
body of stomach	UBERON:0001161	83.95	gold quality
caecum	UBERON:0001153	83.21	gold quality
gall bladder	UBERON:0002110	82.62	gold quality
bone marrow cell	CL:0002092	82.56	gold quality
blood	UBERON:0000178	82.51	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	987.12
E-MTAB-9841	yes	835.15
E-MTAB-10885	yes	564.93
E-MTAB-6701	yes	119.85
E-ANND-3	yes	10.32

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): REST

miRNA regulators (miRDB)

44 targeting KCNN4, 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-5193	100.00	67.26	1744
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-485-5P	99.10	64.78	1889

Literature-anchored findings (GeneRIF, showing 40)

• functional role of the intermediate conductance Ca(2+)-activated K(+) channel, hIK1, in HaCaT keratinocytes (PMID:12421833)
• trafficking depends upon a C-terminal leucine zipper (PMID:12493744)
• arachidonic acid (AA) interacts with the pore-lining amino acids, Thr(250) and Val(275) in hIK1, conferring inhibition of hIK1 by AA (PMID:12609997)
• Ca2+-activated Cl- secretion in native human airway epithelia requires activation of Ca2+-dependent basolateral K+ channels (hSK4). (PMID:12612194)
• SK4 is the gene that codes for the Gardos channel in red blood cells. This channel is important pathophysiologically, because it represents the major pathway for cell shrinkage via KCl and water loss that occurs in sickle cell disease. (PMID:12773623)
• K(Ca) channels presenting the pharmacology of SK4 channels are present on both apical and basolateral membranes, but it is the basolateral SK4-like channels that play a major role in calcium-dependent chloride secretion in 16HBE14o- cells. (PMID:14724753)
• the NH(2) terminus of hIK1 contains overlapping leucine zipper and dileucine motifs essential for channel assembly and trafficking to the plasma membrane (PMID:14754884)
• activation of Gardos channel at different oxygen tensions is correlated with changes in passive and active calcium transport and sensitivity to calcium (PMID:15039018)
• stochastic Ca2+ permeabilization rather than Gardos-channel variation is the main determinant selecting which sickle cells dehydrate through Gardos channels in each sickling episode (PMID:15339840)
• We present in this work a structural model of the open IKCa (KCa3.1) channel derived by homology modeling from the MthK channel structure, and used this model to compute the transmembrane potential profile along the channel pore. (PMID:15452196)
• first demonstration that gating of the iKCa1 potassium channel is regulated by beta2-adrenoceptors (PMID:15817638)
• Results describe the subcellular distribution of the canine (cIK1) and the human (hIK1) channel protein in different migrating cells. (PMID:15965951)
• phosphatidylinositol 3-phosphate and these 14 amino acids regulate KCa3.1 channel activity by recruiting an as yet to be defined regulatory subunit that is required for Ca2+ gating of KCa3.1 (PMID:16251351)
• H441 cells express KCNN4 and cellular potassium conductance is important to the control of Na(+) absorption in respiratory epithelium (PMID:16766578)
• KCa3.1 channels are a part of the signaling complex that forms at the IS upon antigen presentation. (PMID:17151145)
• We show that nucleoside diphosphate kinase B (NDPK-B), a mammalian histidine kinase, functions downstream of PI(3)P to activate KCa3.1 by phosphorylating histidine 358 in the carboxyl terminus of KCa3.1. (PMID:17157250)
• Increased activity of IKCa1 channel is necessary for the development of endometrial cancer. (PMID:17310992)
• S6 transmembrane segment of the open KCa3.1 channel contains two functional domains delimited by V282 with MTSEA and MTSET binding leading to a channel inhibition at V275, T278, and V282 and to a steep channel activation at positions A283 and A286 (PMID:17353352)
• KCNN4 activity decines sharply throughout the lifespan of human red blood cells. (PMID:17470662)
• The G(alphas)-coupled adenosine A2A receptor closes KCa3.1, providing a clearly defined mechanism by which adenosine inhibits human lung mast cell migration and degranulation. (PMID:17474152)
• KCa3.1 channels are important in human airway smooth muscle cell proliferation. (PMID:17585114)
• SK4 channels activity, underlying the Ca(2+)-dependent K(+) permeability was in particular increased by IL-13 (PMID:17762175)
• KCNN4 channels, possibly in parallel with volume-sensitive outwardly rectifying Cl channels, effect regulatory volume decrease in lens epithelial cells. (PMID:18184876)
• KCa3.1 and KCa2.3 are translocated out of the endoplasmic reticulum associated with Derlin-1. (PMID:18227067)
• KCa3.1 channels are not immobilized at the front but move in a diffuse way throughout the plasma membrane of migrating cells. (PMID:18287336)
• IK1 channel activity appears to mediate, at least in part, the response of epidermoid cancer cells to cisplatin treatment. (PMID:18367588)
• KCa3.1 channels play a critical role in transcellular chloride secretion and net fluid transport into the kidney cysts of patients with ADPKD by maintaining (PMID:18547995)
• KCa3.1 contributes to atherogenesis in mice and humans (PMID:18688283)
• An NH2-terminal multi-basic RKR motif is required for the ATP-dependent regulation of IK1. (PMID:18690018)
• findings show the G(s)-coupled EP(2) receptor closes K(Ca)3.1 in lung mast cells and attenuates both chemokine- and PGE(2)-dependent lung mast cell migration (PMID:18792407)
• the mammalian protein histidine phosphatase (PHPT-1) directly binds and inhibits KCa3.1 by dephosphorylating histidine 358 on KCa3.1 (PMID:18796614)
• Inhibition of the KCa3.1 channels by AMP-activated protein kinase in human airway epithelial cells. (PMID:19052260)
• overexpression of the IK(Ca1) channel is likely to promote carcinogenesis in human prostate tissue. (PMID:19270724)
• Data show that moderate increases of mitochondrial matrix [Ca(2+)] will cause mtK(Ca)3.1 opening, thus linking inner membrane K(+) permeability and transmembrane potential to Ca(2+) signalling. (PMID:19406468)
• The expression level of K(Ca)3.1 channels was similar in all T cell subsets in multiple sclerosis patients. (PMID:19409928)
• Data show that the class II phosphatidylinositol 3 kinase C2beta (PI3K-C2beta) is activated by the T-cell receptor (TCR) and functions upstream of NDPK-B to activate KCa3.1 channel activity. (PMID:19587117)
• Nitric oxide increases cardiac IK1 by nitrosylation of cysteine 76 of Kir2.1 channels. (PMID:19608980)
• The aim of this study was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in the human KCNN4 gene or haplotypes and the incidence of myocardial infarction or cerebral infarction in Japanese. (PMID:19644414)
• Data demonstrate that bestrophin 1 is localized in the endoplasmic reticulum (ER), where it interacts with the ER-Ca(2+) sensor and can enhance Ca(2+) signaling and activation of Ca(2+)-dependent Cl(-) (TMEM16A) and K(+) (SK4) channels. (PMID:19823864)
• presence of mtKCa3.1 in tumor cell lines using biochemical and electrophysiological approaches (PMID:20036632)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnn4	ENSDARG00000086091
mus_musculus	Kcnn4	ENSMUSG00000054342
rattus_norvegicus	Kcnn4	ENSRNOG00000019440
drosophila_melanogaster	SK	FBGN0029761
caenorhabditis_elegans		WBGENE00007176
caenorhabditis_elegans		WBGENE00008265
caenorhabditis_elegans	kcnl-2	WBGENE00008570
caenorhabditis_elegans		WBGENE00015387

Paralogs (3): KCNN2 (ENSG00000080709), KCNN1 (ENSG00000105642), KCNN3 (ENSG00000143603)

Protein

Protein identifiers

Intermediate conductance calcium-activated potassium channel protein 4 — O15554 (reviewed: O15554)

Alternative names: Gardos channel, IKCa1, KCa3.1, Putative Gardos channel, hKCa4

All UniProt accessions (5): O15554, M0QZ70, M0R1J0, M0R2E8, M0R2F1

UniProt curated annotations — full annotation on UniProt →

Function. Intermediate conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with calmodulin which binds the intracellular calcium allowing its opening. The current is characterized by a voltage-independent activation, an intracellular calcium concentration increase-dependent activation and a single-channel conductance of about 25 picosiemens. Also presents an inwardly rectifying current, thus reducing its already small outward conductance of potassium ions, which is particularly the case when the membrane potential displays positive values, above + 20 mV. Controls calcium influx during vascular contractility by being responsible of membrane hyperpolarization induced by vasoactive factors in proliferative vascular smooth muscle cell types. Following calcium influx, the consecutive activation of KCNN4 channel leads to a hyperpolarization of the cell membrane potential and hence an increase of the electrical driving force for further calcium influx promoting sustained calcium entry in response to stimulation with chemotactic peptides. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. Plays a role in the late stages of EGF-induced macropinocytosis through activation by PI(3)P.

Subunit / interactions. Homodimer. Homotetramer. Heterotetramer of potassium channel proteins. Interacts with MTMR6; this interaction leads to selective dephosphorylation of PI(3)P in a lipid microdomain adjacent to KCNN4, resulting in a decrease of intermediate conductance calcium-activated potassium channel activity. Interacts (via the C-tail domain) with CALM1; the calmodulin binding is constitutive, does not require calcium and mediates calcium-dependent gating and four calmodulin molecules bind to one channel tetramer.

Subcellular location. Cell membrane. Cell projection. Ruffle membrane.

Tissue specificity. Widely expressed in non-excitable tissues.

Post-translational modifications. Phosphorylation at His-358 by NDKB activates the intermediate conductance calcium-activated potassium channel activity, and conversely its dephosphorylation by PHPT1 inhibits this activity.

Disease relevance. Dehydrated hereditary stomatocytosis 2 (DHS2) [MIM:616689] An autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. Erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. Affected individuals typically manifest mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration. Their red cells exhibit a panel of various shape abnormalities such as elliptocytes, hemighosts, schizocytes, and very rare stomatocytic cells. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The channel is inhibited by clotrimazole and charybdotoxin but is insensitive to apamin.

Domain organisation. Transmembrane helices S5 and S6 form the ion channel pore, which is surrounded bymembrane embedded helices S1 to S4. The S4-S5 linker, which contains two distinct helices, undergoes conformational changes upon calmodulin binding to open the channel pore.

Induction. Up-regulated by phorbol myristate acetate (PMA) and phytohemagglutinin (PHA) in T-cells.

Similarity. Belongs to the potassium channel KCNN family. KCa3.1/KCNN4 subfamily.

RefSeq proteins (1): NP_002241* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004178	CaM-bd_dom	Domain
IPR013099	K_chnl_dom	Domain
IPR015449	K_chnl_Ca-activ_SK	Family
IPR036122	CaM-bd_dom_sf	Homologous_superfamily

Pfam: PF02888, PF03530, PF07885

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (36 total): helix 15, transmembrane region 6, turn 4, sequence variant 3, mutagenesis site 2, chain 1, sequence conflict 1, strand 1, intramembrane region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
6D42	X-RAY DIFFRACTION	1.75
9ZRK	ELECTRON MICROSCOPY	2.99
9O48	ELECTRON MICROSCOPY	3.1
9O5O	ELECTRON MICROSCOPY	3.1
9O52	ELECTRON MICROSCOPY	3.18
9O53	ELECTRON MICROSCOPY	3.3
9ZRL	ELECTRON MICROSCOPY	3.38
9ZPT	ELECTRON MICROSCOPY	3.39
6CNM	ELECTRON MICROSCOPY	3.4
9O51	ELECTRON MICROSCOPY	3.4
9YDZ	ELECTRON MICROSCOPY	3.4
6CNN	ELECTRON MICROSCOPY	3.5
9ED1	ELECTRON MICROSCOPY	3.5
9OA8	ELECTRON MICROSCOPY	3.59
9ZPO	ELECTRON MICROSCOPY	3.67
6CNO	ELECTRON MICROSCOPY	4.7
9Y5Q	ELECTRON MICROSCOPY	4.73

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15554-F1	84.55	0.51

Functional residue map

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

Post-translational modifications (1): 358

Mutagenesis-validated functional residues (2):

Position	Phenotype
250	loss of sensitivity to triarylmethanes.
275	loss of sensitivity to triarylmethanes.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1296052	Ca2+ activated K+ channels
R-HSA-112316	Neuronal System
R-HSA-1296071	Potassium Channels

MSigDB gene sets: 790 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_DIGESTION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_PINOCYTOSIS, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, REACTOME_POTASSIUM_CHANNELS, GCM_NPM1, MODULE_64, MORF_UBE2I, GOBP_CELL_CYCLE_PHASE_TRANSITION

GO Biological Process (20): immune system process (GO:0002376), potassium ion transport (GO:0006813), calcium ion transport (GO:0006816), cell volume homeostasis (GO:0006884), defense response (GO:0006952), stabilization of membrane potential (GO:0030322), macropinocytosis (GO:0044351), phospholipid translocation (GO:0045332), saliva secretion (GO:0046541), positive regulation of protein secretion (GO:0050714), positive regulation of T cell receptor signaling pathway (GO:0050862), protein homotetramerization (GO:0051289), establishment of localization in cell (GO:0051649), potassium ion transmembrane transport (GO:0071805), positive regulation of potassium ion transmembrane transport (GO:1901381), regulation of calcium ion import across plasma membrane (GO:1905664), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), regulation of transport (GO:0051049), regulation of biological quality (GO:0065008)

GO Molecular Function (8): potassium channel activity (GO:0005267), calmodulin binding (GO:0005516), calcium-activated potassium channel activity (GO:0015269), small conductance calcium-activated potassium channel activity (GO:0016286), protein phosphatase binding (GO:0019903), intermediate conductance calcium-activated potassium channel activity (GO:0022894), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (9): cytosol (GO:0005829), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), vesicle (GO:0031982), ruffle membrane (GO:0032587), neuron projection (GO:0043005), neuronal cell body (GO:0043025), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Potassium Channels	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
metal ion transport	2
transport	2
calcium-activated potassium channel activity	2
biological_process	1
regulation of cell size	1
cellular homeostasis	1
response to stress	1
regulation of membrane potential	1
pinocytosis	1
phospholipid transport	1
lipid translocation	1
body fluid secretion	1
digestive system process	1
secretion by tissue	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
positive regulation of antigen receptor-mediated signaling pathway	1
protein homooligomerization	1
protein tetramerization	1
establishment of localization	1
cellular localization	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
positive regulation of potassium ion transport	1
potassium ion transmembrane transport	1
regulation of potassium ion transmembrane transport	1
positive regulation of cation transmembrane transport	1
regulation of calcium ion import	1
calcium ion import across plasma membrane	1
regulation of calcium ion transmembrane transport	1
monoatomic ion transport	1
transmembrane transport	1
regulation of localization	1
biological regulation	1
monoatomic cation channel activity	1

Protein interactions and networks

STRING

1538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNN4	NME2	P22392	931
KCNN4	CSN3	P07498	912
KCNN4	KCNA3	P22001	852
KCNN4	KCNMA1	Q12791	827
KCNN4	CALML4	Q96GE6	822
KCNN4	CALML6	Q8TD86	821
KCNN4	CALML3	P27482	821
KCNN4	CALML5	Q9NZT1	821
KCNN4	KCNMB4	Q86W47	761
KCNN4	CACNA1D	Q01668	753
KCNN4	PHPT1	Q9NRX4	751
KCNN4	MTMR6	Q9Y217	751
KCNN4	CALM1	P02593	741
KCNN4	KCNA2	P16389	735
KCNN4	KCNA1	Q09470	730

IntAct

85 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
CFTR	KCNN4	psi-mi:“MI:0915”(physical association)	0.600
CFTR	KCNN4	psi-mi:“MI:0403”(colocalization)	0.600
CALM1	KCNN4	psi-mi:“MI:0407”(direct interaction)	0.590
KCNN4	CALM1	psi-mi:“MI:0407”(direct interaction)	0.590
STX1B	KCNN4	psi-mi:“MI:0915”(physical association)	0.560
PMP22	KCNN4	psi-mi:“MI:0915”(physical association)	0.560
KCNN4	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
KCNN4	GPR152	psi-mi:“MI:0915”(physical association)	0.560
KCNN4	STX1B	psi-mi:“MI:0915”(physical association)	0.560
KCNN4	FXYD3	psi-mi:“MI:0915”(physical association)	0.560
KCNN4	BIK	psi-mi:“MI:0915”(physical association)	0.560
KCNN4	PMP22	psi-mi:“MI:0915”(physical association)	0.560
KCNN4	CNIH3	psi-mi:“MI:0915”(physical association)	0.560
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
CREB3	MYO9A	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
CXCR4	FANCA	psi-mi:“MI:0914”(association)	0.530
PBXIP1	KCNN4	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530

BioGRID (75): KCNN4 (Affinity Capture-MS), KCNN4 (Proximity Label-MS), KCNN4 (Two-hybrid), KCNN4 (Two-hybrid), KCNN4 (Two-hybrid), PMP22 (Two-hybrid), CNIH3 (Two-hybrid), SLC30A2 (Two-hybrid), GPR152 (Two-hybrid), KCNN4 (Proximity Label-MS), KCNN4 (Proximity Label-MS), KCNN4 (Proximity Label-MS), KCNN4 (Proximity Label-MS), KCNN4 (Proximity Label-MS), KCNN4 (Proximity Label-MS)

ESM2 similar proteins: A2BDX4, A4K2T1, A4K2Y2, D4AD53, O15554, O73606, O88454, O89109, P15388, P17971, P17972, P35739, P48547, P59053, P59994, P59995, P97557, Q03719, Q0P583, Q17ST2, Q52PG9, Q5RC10, Q60565, Q63881, Q6IVV8, Q6PIU1, Q7TN37, Q80XM3, Q8BZN2, Q8CFS6, Q8HYZ1, Q8IV77, Q8R1P5, Q8R523, Q8TAE7, Q8TD43, Q8TDN1, Q8TDN2, Q96RP8, Q9ERS0

Diamond homologs: O15554, O89109, P58390, P58391, P58392, P70604, P70605, P70606, Q02006, Q7KVW5, Q92952, Q9EQR3, Q9H2S1, Q9QYW1, Q9UGI6, A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, A6H8H5, B2RQA1, G5EFC3, O18868, O35173, O35174, O43525, O43526, O70344, O73606, O73925, O88758, O88759, O88943

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
NME2	up-regulates	KCNN4	phosphorylation
TRAM-34	up-regulates	KCNN4	“chemical activation”
Riluzole	“up-regulates activity”	KCNN4	“chemical activation”
Naphtho[1,2-d]thiazol-2-amine	“up-regulates activity”	KCNN4	“chemical activation”
nitrendipine	“down-regulates activity”	KCNN4	“chemical inhibition”
clotrimazole	“down-regulates activity”	KCNN4	“chemical inhibition”
PRKACA	“down-regulates activity”	KCNN4	phosphorylation
PHPT1	“down-regulates activity”	KCNN4	dephosphorylation
KCNN4	“up-regulates quantity”	calcium(2+)	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ion homeostasis	6	20.7×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	143
Likely benign	34
Benign	34

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
252601	NM_002250.3(KCNN4):c.1055G>A (p.Arg352His)	Pathogenic
978810	NM_002250.3(KCNN4):c.940T>C (p.Ser314Pro)	Pathogenic
372185	NM_002250.3(KCNN4):c.844G>A (p.Val282Met)	Likely pathogenic
372186	NM_002250.3(KCNN4):c.845T>A (p.Val282Glu)	Likely pathogenic

SpliceAI

1639 predictions. Top by Δscore:

Variant	Effect	Δscore
19:43767545:A:AC	donor_gain	1.0000
19:43767546:C:CC	donor_gain	1.0000
19:43767548:TGG:T	donor_gain	1.0000
19:43768958:AGTAC:A	donor_gain	1.0000
19:43768959:GTAC:G	donor_loss	1.0000
19:43768962:C:G	donor_loss	1.0000
19:43769028:GGAAC:G	acceptor_gain	1.0000
19:43769029:GAAC:G	acceptor_gain	1.0000
19:43769030:AAC:A	acceptor_gain	1.0000
19:43769031:AC:A	acceptor_gain	1.0000
19:43769032:CC:C	acceptor_gain	1.0000
19:43769032:CCTG:C	acceptor_loss	1.0000
19:43769033:C:CC	acceptor_gain	1.0000
19:43769033:CTGTG:C	acceptor_loss	1.0000
19:43769034:T:G	acceptor_loss	1.0000
19:43769713:TCTCA:T	donor_loss	1.0000
19:43769714:CTCA:C	donor_loss	1.0000
19:43769715:TCA:T	donor_loss	1.0000
19:43769716:CA:C	donor_loss	1.0000
19:43769717:ACC:A	donor_loss	1.0000
19:43769718:C:CG	donor_loss	1.0000
19:43769718:CCT:C	donor_gain	1.0000
19:43769826:CACC:C	acceptor_gain	1.0000
19:43769828:CC:C	acceptor_gain	1.0000
19:43769829:CCTG:C	acceptor_gain	1.0000
19:43769830:C:CC	acceptor_gain	1.0000
19:43771994:ACTC:A	donor_loss	1.0000
19:43771996:TCA:T	donor_loss	1.0000
19:43771997:CACCA:C	donor_loss	1.0000
19:43771998:A:AC	donor_gain	1.0000

AlphaMissense

2732 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:43769829:C:G	G274R	0.999
19:43769813:G:T	A279D	0.998
19:43769828:C:T	G274D	0.998
19:43772058:C:A	G254V	0.998
19:43772064:C:T	G252D	0.998
19:43772070:G:A	T250I	0.998
19:43772073:A:G	L249P	0.998
19:43772079:G:T	T247K	0.998
19:43772095:A:G	W242R	0.998
19:43772095:A:T	W242R	0.998
19:43769823:A:G	C276R	0.997
19:43769829:C:A	G274C	0.997
19:43772007:C:T	G271E	0.997
19:43772008:C:G	G271R	0.997
19:43772008:C:T	G271R	0.997
19:43772020:A:G	C267R	0.997
19:43772058:C:T	G254D	0.997
19:43772059:C:A	G254C	0.997
19:43772064:C:A	G252V	0.997
19:43772065:C:G	G252R	0.997
19:43772085:G:C	P245R	0.997
19:43774229:A:G	W216R	0.997
19:43774229:A:T	W216R	0.997
19:43769810:A:G	L280P	0.996
19:43772018:G:C	C267W	0.996
19:43772062:A:G	Y253H	0.996
19:43772075:G:C	F248L	0.996
19:43772075:G:T	F248L	0.996
19:43772077:A:G	F248L	0.996
19:43774293:G:C	F194L	0.996

dbSNP variants (sampled 300 via entrez): RS1000373666 (19:43775781 T>C), RS1000601226 (19:43781118 G>A), RS1000651519 (19:43775992 G>A), RS1000750769 (19:43770316 T>C), RS1000953254 (19:43770130 C>T), RS1001019085 (19:43775828 G>A), RS1001312810 (19:43766699 G>C), RS1001319878 (19:43778482 G>A), RS1001345081 (19:43766932 C>A), RS1001407822 (19:43771673 C>A), RS1001451659 (19:43775494 A>G), RS1001620257 (19:43772679 G>A), RS1001734504 (19:43771892 G>A), RS1001796409 (19:43776151 A>T), RS1001889531 (19:43776295 ACT>A)

Disease associations

OMIM: gene MIM:602754 | disease phenotypes: MIM:616689, MIM:608647, MIM:194380

GenCC curated gene-disease

Disease	Classification	Inheritance
dehydrated hereditary stomatocytosis 2	Strong	Autosomal dominant
dehydrated hereditary stomatocytosis	Supportive	Autosomal dominant
cystic fibrosis	Supportive	Autosomal recessive

Mondo (5): dehydrated hereditary stomatocytosis 2 (MONDO:0014737), primary ciliary dyskinesia 5 (MONDO:0012088), dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema (MONDO:0008689), dehydrated hereditary stomatocytosis (MONDO:0017910), cystic fibrosis (MONDO:0009061)

Orphanet (2): Dehydrated hereditary stomatocytosis (Orphanet:3202), Primary ciliary dyskinesia (Orphanet:244)

HPO phenotypes

73 total (30 of 73 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000787	Nephrolithiasis
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000952	Jaundice
HP:0000969	Edema
HP:0001046	Intermittent jaundice
HP:0001081	Cholelithiasis
HP:0001392	Abnormality of the liver
HP:0001394	Cirrhosis
HP:0001508	Failure to thrive
HP:0001738	Exocrine pancreatic insufficiency
HP:0001744	Splenomegaly
HP:0001878	Hemolytic anemia
HP:0001894	Thrombocytosis
HP:0001900	Increased circulating hemoglobin concentration
HP:0001901	Polycythemia
HP:0001907	Thromboembolism
HP:0001923	Reticulocytosis
HP:0001927	Acanthocytosis
HP:0001930	Nonspherocytic hemolytic anemia
HP:0001972	Macrocytic anemia
HP:0001981	Schistocytosis
HP:0002020	Gastroesophageal reflux
HP:0002024	Malabsorption
HP:0002027	Abdominal pain

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST001937_27	Breast cancer	2.000000e-10
GCST004602_276	Mean corpuscular volume	2.000000e-09
GCST004605_81	Mean corpuscular hemoglobin concentration	1.000000e-27
GCST004608_139	Granulocyte percentage of myeloid white cells	7.000000e-35
GCST004609_152	Monocyte percentage of white cells	8.000000e-38
GCST004615_125	Hemoglobin concentration	4.000000e-09
GCST004625_216	Monocyte count	1.000000e-37
GCST005992_38	Mean corpuscular hemoglobin concentration	5.000000e-12
GCST006011_59	Mean corpuscular volume	2.000000e-08
GCST006803_54	Schizophrenia	8.000000e-07
GCST010083_275	Hemoglobin levels	2.000000e-16
GCST010146_22	Serum immune biomarker levels	7.000000e-09
GCST90002383_286	Hematocrit	2.000000e-10
GCST90002384_454	Hemoglobin	8.000000e-23
GCST90002391_116	Mean corpuscular hemoglobin concentration	6.000000e-43
GCST90002392_76	Mean corpuscular volume	6.000000e-15
GCST90002393_103	Monocyte count	1.000000e-10
GCST90002393_662	Monocyte count	4.000000e-86
GCST90002394_560	Monocyte percentage of white cells	6.000000e-68
GCST90002395_412	Mean platelet volume	3.000000e-12
GCST90002399_438	Neutrophil percentage of white cells	2.000000e-10
GCST90002400_287	Plateletcrit	3.000000e-10
GCST90002401_266	Platelet distribution width	7.000000e-13
GCST90002403_301	Red blood cell count	2.000000e-20
GCST90002405_551	Reticulocyte count	8.000000e-11
GCST90002407_627	White blood cell count	1.000000e-13

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004509	hemoglobin measurement
EFO:0005091	monocyte count
EFO:0004872	inflammatory biomarker measurement
EFO:0004348	hematocrit
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0004305	erythrocyte count
EFO:0007986	reticulocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213
C563886	Ciliary Dyskinesia, Primary, 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4305 (SINGLE PROTEIN), CHEMBL4524132 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 56,489 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL405821	SENICAPOC	3	164

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Calcium- and sodium-activated potassium channels (K_Ca, K_Na)

Most potent curated ligand interactions (20 total), top 20:

Ligand	Action	Affinity	Parameter
maurotoxin	Inhibition	9.0	pIC50
charybdotoxin	Inhibition	8.5	pKd
DHP-103	Channel blocker	8.22	pIC50
NS6180	Inhibition	8.05	pIC50
NS309	Agonist	8.0	pEC50
compound rac-16 [PMID: 15603962]	Inhibition	8.0	pIC50
TRAM-34	Inhibition	8.0	pKd
senicapoc	Inhibition	7.96	pIC50
clotrimazole	Inhibition	7.62	pKd
charybdotoxin-GLU32 analog	Inhibition	7.5	pKd
ASP-0819	Activation	7.03	pEC50
Ca2+	Agonist	7.0	pEC50
SKA-121	Agonist	6.96	pEC50
SKA-111	Agonist	6.95	pEC50
SKA-31	Activator	6.6	pEC50
DC-EBIO	Agonist	6.1	pEC50
nitrendipine	Inhibition	6.1	pKd
riluzole	Activator	5.7	pIC50
EBIO	Agonist	4.5	pEC50
chlorzoxazone	Agonist	4.0	pEC50

Binding affinities (BindingDB)

111 measured of 111 human assays (111 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[(4S)-4,5,5-tris(2-fluorophenyl)-2-oxo-1,3-oxazolidin-3-yl]acetamide	IC50	15 nM	US-9611232: Oxazolidinone and imidazolidinone compounds
2-[(4S)-4-(2-fluorophenyl)-2-oxo-5,5-diphenyl-1,3-oxazolidin-3-yl]acetamide	IC50	15 nM	US-9611232: Oxazolidinone and imidazolidinone compounds
2-[2-[2-[1-(2-fluorophenyl)tetrazol-5-yl]phenyl]phenoxy]acetonitrile	IC50	16 nM	US-9556132: Tetrazole derivatives and their use as potassium channel modulators
5-[2-[2-(fluoromethyl)phenyl]phenyl]-1-(2-fluorophenyl)tetrazole	IC50	17 nM	US-9556132: Tetrazole derivatives and their use as potassium channel modulators
2-[(4S)-4-(2-fluorophenyl)-5,5-bis(4-fluorophenyl)-2-oxo-1,3-oxazolidin-3-yl]acetamide	IC50	22 nM	US-9611232: Oxazolidinone and imidazolidinone compounds
1-(2-fluorophenyl)-5-[2-[2-(2-methoxyethoxy)phenyl]phenyl]tetrazole	IC50	30 nM	US-9556132: Tetrazole derivatives and their use as potassium channel modulators
5-[2-(2-ethoxyphenyl)phenyl]-1-(2-fluorophenyl)tetrazole	IC50	37 nM	US-9556132: Tetrazole derivatives and their use as potassium channel modulators
4-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-1,1-dioxothieno[3,2-b][1,4]thiazin-3-one	IC50	39 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[1-[3-(trifluoromethyl)phenyl]ethyl]pyrido[3,2-b][1,4]thiazin-3-one	IC50	41 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
2-[(4S)-4-(2-fluorophenyl)-5,5-bis(3-fluorophenyl)-2-oxo-1,3-oxazolidin-3-yl]acetamide	IC50	42 nM	US-9611232: Oxazolidinone and imidazolidinone compounds
2-[(4S)-4,5,5-tris(4-fluorophenyl)-2-oxo-1,3-oxazolidin-3-yl]acetamide	IC50	45 nM	US-9611232: Oxazolidinone and imidazolidinone compounds
4-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]pyrido[3,2-b][1,4]thiazin-3-one	IC50	46 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[[4-chloro-3-(trifluoromethylsulfonyl)phenyl]methyl]pyrido[3,2-b][1,4]thiazin-3-one	IC50	47 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
1-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-4,4-dioxothieno[2,3-b][1,4]thiazin-2-one	IC50	48 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-1,1-dioxopyrido[3,2-b][1,4]thiazin-3-one	IC50	49 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[[4-chloro-3-(trifluoromethylsulfanyl)phenyl]methyl]pyrido[3,2-b][1,4]thiazin-3-one	IC50	52 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[[3-(trifluoromethoxy)phenyl]methyl]pyrido[3,2-b][1,4]thiazin-3-one	IC50	52 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
US9556132, 30	IC50	57 nM	US-9556132: Tetrazole derivatives and their use as potassium channel modulators
1-(2-fluorophenyl)-5-[2-[2-(methoxymethyl)phenyl]phenyl]tetrazole	IC50	58 nM	US-9556132: Tetrazole derivatives and their use as potassium channel modulators
2-[(4S)-5,5-bis(4-fluorophenyl)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]acetamide	IC50	58 nM	US-9611232: Oxazolidinone and imidazolidinone compounds
7-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-[1,3]thiazolo[4,5-b][1,4]thiazin-6-one	IC50	60 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
ethyl 2-[(4R,5S)-4-(4-fluorophenyl)-2-oxo-5-[3-(trifluoromethyl)phenyl]-1,3-oxazolidin-3-yl]acetate	IC50	62 nM	US-9611232: Oxazolidinone and imidazolidinone compounds
2-[(4S)-4-(2-chlorophenyl)-5,5-bis(4-fluorophenyl)-2-oxo-1,3-oxazolidin-3-yl]acetamide	IC50	63 nM	US-9611232: Oxazolidinone and imidazolidinone compounds
2-[5-[2-(2-methoxyphenyl)phenyl]tetrazol-1-yl]benzonitrile	IC50	64 nM	US-9556132: Tetrazole derivatives and their use as potassium channel modulators
4-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-6-(hydroxymethyl)pyrido[3,2-b][1,4]thiazin-3-one	IC50	66 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
2-methyl-4-[1-[3-(trifluoromethyl)phenyl]ethyl]-[1,3]thiazolo[5,4-b][1,4]thiazin-5-one	IC50	67 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
1-[2-(difluoromethoxy)phenyl]-5-[2-(2-methoxyphenyl)phenyl]tetrazole	IC50	69 nM	US-9556132: Tetrazole derivatives and their use as potassium channel modulators
1,1-dioxo-4-[1-[3-(trifluoromethyl)phenyl]ethyl]thieno[3,2-b][1,4]thiazin-3-one	IC50	71 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
2-methyl-4-[[3-(trifluoromethyl)phenyl]methyl]-[1,3]thiazolo[5,4-b][1,4]thiazin-5-one	IC50	73 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[[4-chloro-3-(trifluoromethoxy)phenyl]methyl]-1,1-dioxopyrido[3,2-b][1,4]thiazin-3-one	IC50	77 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
methyl 4-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-1,1,3-trioxopyrido[3,2-b][1,4]thiazine-6-carboxylate	IC50	88 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
7-chloro-4-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-1,1-dioxopyrido[3,2-b][1,4]thiazin-3-one	IC50	92 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-7,7-dioxo-2-propan-2-yl-[1,3]thiazolo[5,4-b][1,4]thiazin-5-one	IC50	96 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
7-chloro-1,1-dioxo-4-[1-[3-(trifluoromethyl)phenyl]ethyl]pyrido[3,2-b][1,4]thiazin-3-one	IC50	110 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-7,7-dioxo-[1,3]thiazolo[5,4-b][1,4]thiazin-5-one	IC50	110 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
1-(2-fluorophenyl)-5-[2-(2-methoxyphenyl)phenyl]tetrazole	IC50	110 nM	US-9556132: Tetrazole derivatives and their use as potassium channel modulators
US9556132, 31	IC50	110 nM	US-9556132: Tetrazole derivatives and their use as potassium channel modulators
1,1-dioxo-4-[1-[3-(trifluoromethyl)phenyl]ethyl]pyrido[3,2-b][1,4]thiazin-3-one	IC50	120 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
methyl 2,4,4-trioxo-1-[1-[3-(trifluoromethyl)phenyl]ethyl]thieno[2,3-b][1,4]thiazine-6-carboxylate	IC50	120 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
7-chloro-4-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]pyrido[3,2-b][1,4]thiazin-3-one	IC50	130 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[1-[4-chloro-3-(trifluoromethyl)phenyl]ethyl]-1,1-dioxopyrido[3,2-b][1,4]thiazin-3-one	IC50	140 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
methyl 2,4,4-trioxo-1-[[3-(trifluoromethoxy)phenyl]methyl]thieno[2,3-b][1,4]thiazine-6-carboxylate	IC50	150 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
7-[[3-(trifluoromethoxy)phenyl]methyl]-[1,3]thiazolo[4,5-b][1,4]thiazin-6-one	IC50	160 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-1,1-dioxopyrazino[2,3-b][1,4]thiazin-3-one	IC50	170 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
7-[1-[3-(trifluoromethyl)phenyl]ethyl]-[1,3]thiazolo[4,5-b][1,4]thiazin-6-one	IC50	170 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-1,1-dioxopyrido[3,2-b][1,4]thiazin-3-one	IC50	180 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
7-chloro-4-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-1,1-dioxopyrido[3,2-b][1,4]thiazin-3-one	IC50	180 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
4-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-3-oxopyrido[3,2-b][1,4]thiazine-6-carboxamide	IC50	180 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
methyl 2,4,4-trioxo-1-[[3-(trifluoromethyl)phenyl]methyl]thieno[2,3-b][1,4]thiazine-6-carboxylate	IC50	190 nM	US-9533999: Fused thiazin-3-ones as KCA3.1 inhibitors
1-(2-fluorophenyl)-5-[2-[2-(methoxymethoxy)phenyl]phenyl]tetrazole	IC50	190 nM	US-9556132: Tetrazole derivatives and their use as potassium channel modulators

ChEMBL bioactivities

172 potent at pChembl≥5 of 180 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.22	IC50	6	nM	SENICAPOC
8.09	IC50	8.1	nM	CHEMBL4744833
8.07	IC50	8.6	nM	CHEMBL4749039
8.06	IC50	8.7	nM	CHEMBL4791725
8.05	IC50	9	nM	CHEMBL42205
8.00	IC50	10	nM	CHEMBL272039
7.92	IC50	12	nM	SENICAPOC
7.89	IC50	13	nM	CHEMBL260736
7.85	IC50	14	nM	CHEMBL270704
7.85	IC50	14	nM	CHEMBL272040
7.85	IC50	14	nM	CHEMBL4788143
7.82	IC50	15	nM	CHEMBL408700
7.82	IC50	15	nM	CHEMBL270071
7.82	IC50	15	nM	CHEMBL273092
7.82	IC50	15	nM	CHEMBL5765097
7.82	IC50	15	nM	CHEMBL5981960
7.80	IC50	16	nM	CHEMBL5855158
7.77	IC50	17	nM	CHEMBL260953
7.77	IC50	17	nM	CHEMBL5773163
7.75	IC50	18	nM	CHEMBL4756080
7.70	IC50	20	nM	CHEMBL406683
7.70	IC50	20	nM	CHEMBL498270
7.66	IC50	22	nM	CHEMBL5899835
7.62	IC50	24	nM	CHEMBL4764429
7.52	IC50	30	nM	CHEMBL261828
7.52	IC50	30	nM	CHEMBL261606
7.52	IC50	30	nM	CHEMBL5852642
7.47	IC50	34	nM	CHEMBL270913
7.43	IC50	37	nM	CHEMBL5865173
7.41	IC50	39	nM	CHEMBL3287207
7.41	IC50	39	nM	CHEMBL5783315
7.40	IC50	40	nM	CHEMBL258604
7.39	IC50	41	nM	CHEMBL3287210
7.38	IC50	42	nM	CHEMBL5994146
7.35	IC50	45	nM	CHEMBL6034068
7.34	IC50	46	nM	CHEMBL5775918
7.33	IC50	47	nM	CHEMBL4745327
7.33	IC50	47	nM	CHEMBL5960938
7.32	IC50	48	nM	CHEMBL3287208
7.31	IC50	49	nM	CHEMBL3287205
7.28	IC50	52	nM	CHEMBL3287209
7.28	IC50	52	nM	CHEMBL4743839
7.28	IC50	52	nM	CHEMBL5961215
7.24	IC50	58	nM	CHEMBL5976036
7.24	IC50	57	nM	CHEMBL5876740
7.24	IC50	58	nM	CHEMBL6055879
7.22	IC50	60	nM	CHEMBL3287212
7.22	IC50	60	nM	CHEMBL6058552
7.21	IC50	62	nM	CHEMBL5979285
7.20	IC50	63	nM	CHEMBL5746247

PubChem BioAssay actives

58 with measured affinity, of 110 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
2,2-bis(4-fluorophenyl)-2-phenylacetamide	726263: Inhibition of Kca 3.1 (unknown origin)	ic50	0.0060	uM
methyl N-[1-[4-fluoro-3-(trifluoromethyl)phenyl]cyclopropyl]-N-[[(2R)-1-methylpyrrolidin-2-yl]methyl]carbamate	1678548: Inhibition of Kca3.1 in human erythrocytes	ic50	0.0081	uM
methyl N-(2-amino-2-methylpropyl)-N-[1-[4-fluoro-3-(trifluoromethyl)phenyl]cyclopropyl]carbamate	1678548: Inhibition of Kca3.1 in human erythrocytes	ic50	0.0086	uM
methyl N-[1-[4-fluoro-3-(trifluoromethoxy)phenyl]cyclopropyl]-N-[[(2S)-pyrrolidin-2-yl]methyl]carbamate	1678548: Inhibition of Kca3.1 in human erythrocytes	ic50	0.0087	uM
2-(2-fluorophenyl)-2-(4-fluorophenyl)-2-phenylacetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0090	uM
2-(2-fluorophenyl)-2,2-bis(4-fluorophenyl)acetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0100	uM
2,2,2-tris(3-fluorophenyl)acetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0130	uM
1-N-(cyclopropylmethyl)-1-N-[1-[4-fluoro-3-(trifluoromethyl)phenyl]cyclopropyl]-2-methylpropane-1,2-diamine	1678548: Inhibition of Kca3.1 in human erythrocytes	ic50	0.0140	uM
2-(3,4-difluorophenyl)-2,2-diphenylacetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0140	uM
2,2,2-tris(4-fluorophenyl)acetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0140	uM
2,2-bis(3-fluorophenyl)-2-(4-fluorophenyl)acetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0150	uM
2-(2-fluorophenyl)-2,2-diphenylacetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0150	uM
2,2-bis(2-fluorophenyl)-2-(4-fluorophenyl)acetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0150	uM
2-(3-fluorophenyl)-2,2-bis(4-fluorophenyl)acetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0170	uM
1-N-cyclobutyl-2-methyl-1-N-[1-[3-(trifluoromethyl)phenyl]cyclopropyl]propane-1,2-diamine	1678548: Inhibition of Kca3.1 in human erythrocytes	ic50	0.0180	uM
(2-chlorophenyl)-diphenylmethanamine	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0200	uM
1-[(2-chlorophenyl)-diphenylmethyl]pyrazole	397426: Inhibition of human cloned IK1 expressed in african green monkey COS7 cells by whole cell patch clamp assay	ic50	0.0200	uM
1-N-cyclopropyl-2-methyl-1-N-[1-[3-(trifluoromethyl)phenyl]cyclopropyl]propane-1,2-diamine	1678548: Inhibition of Kca3.1 in human erythrocytes	ic50	0.0240	uM
2,2-bis(3-fluorophenyl)-2-phenylacetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0300	uM
2,2-bis(2-fluorophenyl)-2-phenylacetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0300	uM
2-(2,4-difluorophenyl)-2,2-diphenylacetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0340	uM
4-[1-[4-fluoro-3-(trifluoromethoxy)phenyl]ethyl]-1,1-dioxothieno[3,2-b][1,4]thiazin-3-one	1154717: Inhibition of human KCa3.1 overexpressed in HEK293 cells assessed as thallium influx preincubated for 15 mins followed by thallium/ionomycin addition measured for 50 secs by FLIPR assay	ic50	0.0390	uM
2-(4-fluorophenyl)-2,2-diphenylacetamide	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0400	uM
4-[1-[3-(trifluoromethyl)phenyl]ethyl]pyrido[3,2-b][1,4]thiazin-3-one	1154717: Inhibition of human KCa3.1 overexpressed in HEK293 cells assessed as thallium influx preincubated for 15 mins followed by thallium/ionomycin addition measured for 50 secs by FLIPR assay	ic50	0.0410	uM
ethyl N-(2-amino-2-methylpropyl)-N-[1-[4-fluoro-3-(trifluoromethyl)phenyl]cyclopropyl]carbamate	1678548: Inhibition of Kca3.1 in human erythrocytes	ic50	0.0470	uM
1-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-4,4-dioxothieno[2,3-b][1,4]thiazin-2-one	1154717: Inhibition of human KCa3.1 overexpressed in HEK293 cells assessed as thallium influx preincubated for 15 mins followed by thallium/ionomycin addition measured for 50 secs by FLIPR assay	ic50	0.0480	uM
4-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-1,1-dioxopyrido[3,2-b][1,4]thiazin-3-one	1154717: Inhibition of human KCa3.1 overexpressed in HEK293 cells assessed as thallium influx preincubated for 15 mins followed by thallium/ionomycin addition measured for 50 secs by FLIPR assay	ic50	0.0490	uM
ethyl N-[1-[4-fluoro-3-(trifluoromethyl)phenyl]cyclopropyl]-N-[[(2S)-pyrrolidin-2-yl]methyl]carbamate	1678548: Inhibition of Kca3.1 in human erythrocytes	ic50	0.0520	uM
4-[[3-(trifluoromethoxy)phenyl]methyl]pyrido[3,2-b][1,4]thiazin-3-one	1154717: Inhibition of human KCa3.1 overexpressed in HEK293 cells assessed as thallium influx preincubated for 15 mins followed by thallium/ionomycin addition measured for 50 secs by FLIPR assay	ic50	0.0520	uM
7-[1-[4-fluoro-3-(trifluoromethoxy)phenyl]ethyl]-[1,3]thiazolo[4,5-b][1,4]thiazin-6-one	1154717: Inhibition of human KCa3.1 overexpressed in HEK293 cells assessed as thallium influx preincubated for 15 mins followed by thallium/ionomycin addition measured for 50 secs by FLIPR assay	ic50	0.0600	uM
4-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-6-(hydroxymethyl)pyrido[3,2-b][1,4]thiazin-3-one	1154717: Inhibition of human KCa3.1 overexpressed in HEK293 cells assessed as thallium influx preincubated for 15 mins followed by thallium/ionomycin addition measured for 50 secs by FLIPR assay	ic50	0.0660	uM
triphenylmethanamine	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.0700	uM
Clotrimazole	397426: Inhibition of human cloned IK1 expressed in african green monkey COS7 cells by whole cell patch clamp assay	ic50	0.0700	uM
N-(2-amino-2-methylpropyl)-N-[1-[4-fluoro-3-(trifluoromethyl)phenyl]cyclopropyl]methanesulfonamide	1678548: Inhibition of Kca3.1 in human erythrocytes	ic50	0.0750	uM
methyl N-(2-amino-2-methylpropyl)-N-[1-[4-fluoro-3-(trifluoromethoxy)phenyl]cyclopropyl]carbamate	1678548: Inhibition of Kca3.1 in human erythrocytes	ic50	0.0920	uM
4-[[4-fluoro-3-(trifluoromethoxy)phenyl]methyl]-7,7-dioxo-2-propan-2-yl-[1,3]thiazolo[5,4-b][1,4]thiazin-5-one	1154717: Inhibition of human KCa3.1 overexpressed in HEK293 cells assessed as thallium influx preincubated for 15 mins followed by thallium/ionomycin addition measured for 50 secs by FLIPR assay	ic50	0.0960	uM
methyl 2,2,2-triphenylacetate	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.3300	uM
3-[diphenylphosphoryl(phenyl)methyl]pyridine	724065: Inhibition of IK channel (unknown origin)	ic50	0.5000	uM
N-methyl-1,1,1-triphenylmethanamine	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	0.5500	uM
3-[diphenylphosphoryl(pyridin-3-yl)methyl]pyridine	724065: Inhibition of IK channel (unknown origin)	ic50	1.0000	uM
5-(3-chlorobenzoyl)-6H-benzo[d][1]benzazepin-7-one	397426: Inhibition of human cloned IK1 expressed in african green monkey COS7 cells by whole cell patch clamp assay	ic50	1.3000	uM
5-(4-chlorophenyl)sulfonyl-6H-benzo[d][1]benzazepin-7-one	397426: Inhibition of human cloned IK1 expressed in african green monkey COS7 cells by whole cell patch clamp assay	ic50	1.4000	uM
N-tritylethanamine	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	1.7500	uM
3-[diphenylphosphoryl(piperidin-1-yl)methyl]pyridine	724065: Inhibition of IK channel (unknown origin)	ic50	1.8000	uM
5-(4-methylphenyl)sulfonyl-6H-benzo[d][1]benzazepin-7-one	397426: Inhibition of human cloned IK1 expressed in african green monkey COS7 cells by whole cell patch clamp assay	ic50	2.1000	uM
5-thiophen-2-ylsulfonyl-6H-benzo[d][1]benzazepin-7-one	397426: Inhibition of human cloned IK1 expressed in african green monkey COS7 cells by whole cell patch clamp assay	ic50	2.4000	uM
3-[diphenylphosphoryl(propyl)amino]benzonitrile	724065: Inhibition of IK channel (unknown origin)	ic50	2.7000	uM
N,N-dimethyl-1,1,1-triphenylmethanamine	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	3.1500	uM
2-trityl-4,5-dihydro-1,3-oxazole	315276: Inhibition of Gardos channel in human RBC assessed as inhibition of ionomycin-stimulated [86Rb] efflux	ic50	4.3000	uM
1-[2-(3-chlorophenyl)-3-pyridinyl]-N-diphenylphosphorylmethanamine	724065: Inhibition of IK channel (unknown origin)	ic50	4.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	3
Clotrimazole	affects cotreatment, decreases reaction, increases activity, decreases activity	3
Estradiol	affects expression, affects cotreatment, decreases expression	3
7,8-benzoquinoline	increases activity	2
4-chlorobenzo(f)isoquinoline	increases activity	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression, affects methylation	2
Calcium	affects abundance, affects reaction, increases transport	2
Hydrogen Peroxide	affects expression, increases expression	2
Potassium	affects reaction, increases transport, affects transport	2
Tamoxifen	affects expression, affects cotreatment, decreases expression	2
Charybdotoxin	decreases reaction, increases activity, decreases activity	2
Raloxifene Hydrochloride	decreases expression, affects expression, affects cotreatment	2
aristolochic acid I	increases expression	1
TL8-506	affects cotreatment, increases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
beta-lapachone	increases expression	1
arsenite	decreases methylation	1
methylparaben	decreases expression	1
afimoxifene	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(f)quinoline	increases activity	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032478	Binding	Inhibition of human cloned IK1 expressed in african green monkey COS7 cells by whole cell patch clamp assay	Inhibitors of potassium channels KV1.3 and IK-1 as immunosuppressants. — Bioorg Med Chem Lett

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B1V2	Abcam HeLa KCNN4 KO	Cancer cell line	Female
CVCL_E9Y2	HEK293-KCNN4-RFP	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	PHASE4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	PHASE4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	PHASE4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	PHASE4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	PHASE4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	PHASE4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	PHASE4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	PHASE4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	PHASE4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	PHASE4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	PHASE4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	PHASE4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	PHASE4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	PHASE4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	PHASE4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	PHASE4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	PHASE4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	PHASE4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	PHASE4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	PHASE4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	PHASE4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	PHASE4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	PHASE4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	PHASE4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	PHASE4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	PHASE4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	PHASE4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	PHASE4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	PHASE4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	PHASE4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	PHASE4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	PHASE4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	PHASE4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	PHASE4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	PHASE4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	PHASE4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	PHASE4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis