KCNT1

Summary

KCNT1 (potassium sodium-activated channel subfamily T member 1, HGNC:18865) is a protein-coding gene on chromosome 9q34.3, encoding Potassium channel subfamily T member 1 (Q5JUK3). Sodium-activated K(+) channel.

Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a sodium-activated potassium channel subunit which is thought to function in ion conductance and developmental signaling pathways. Mutations in this gene cause the early-onset epileptic disorders, malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 57582 — RefSeq curated summary.

At a glance

• Gene–disease (curated): childhood-onset epilepsy syndrome (Definitive, ClinGen) — +4 more curated relationships
• Clinical variants (ClinVar): 2,592 total — 28 pathogenic, 35 likely-pathogenic
• Phenotypes (HPO): 82
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_020822

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18865
Approved symbol	KCNT1
Name	potassium sodium-activated channel subfamily T member 1
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	KCa4.1, KIAA1422, SLACK, Slo2.2
Ensembl gene	ENSG00000107147
Ensembl biotype	protein_coding
OMIM	608167
Entrez	57582

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 16 protein_coding, 12 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000263604, ENST00000371757, ENST00000460750, ENST00000473941, ENST00000475008, ENST00000486577, ENST00000487664, ENST00000488444, ENST00000490355, ENST00000490363, ENST00000491806, ENST00000628528, ENST00000630792, ENST00000631073, ENST00000631193, ENST00000636003, ENST00000636274, ENST00000636613, ENST00000636961, ENST00000636995, ENST00000637018, ENST00000637082, ENST00000637090, ENST00000637668, ENST00000637798, ENST00000638022, ENST00000638123, ENST00000674572, ENST00000675090, ENST00000675102, ENST00000675399, ENST00000676421, ENST00000968545

RefSeq mRNA: 2 — MANE Select: NM_020822 NM_001272003, NM_020822

CCDS: CCDS35175, CCDS65188

Canonical transcript exons

ENST00000371757 — 31 exons

Exon	Start	End
ENSE00001094985	135750942	135751041
ENSE00001094986	135750098	135750177
ENSE00001380112	135714577	135714720
ENSE00001881303	135702185	135702368
ENSE00003464787	135786197	135786521
ENSE00003474810	135778424	135778495
ENSE00003479384	135791797	135791881
ENSE00003483922	135759679	135759859
ENSE00003493559	135758414	135758508
ENSE00003495819	135772715	135772949
ENSE00003525247	135785310	135785330
ENSE00003536719	135770298	135770447
ENSE00003540824	135784761	135784889
ENSE00003551185	135756873	135756932
ENSE00003565737	135775310	135775415
ENSE00003577423	135765031	135765195
ENSE00003585536	135757156	135757230
ENSE00003597037	135779359	135779470
ENSE00003597828	135784535	135784618
ENSE00003602277	135769947	135770055
ENSE00003608474	135792041	135795502
ENSE00003609975	135765624	135765760
ENSE00003612072	135755121	135755169
ENSE00003615541	135757298	135757381
ENSE00003645980	135753937	135753993
ENSE00003650706	135768829	135768937
ENSE00003655693	135770857	135771095
ENSE00003667668	135768610	135768673
ENSE00003686184	135778688	135778822
ENSE00003688359	135777338	135777510
ENSE00003691882	135784024	135784125

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 98.37.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.6081 / max 167.6058, expressed in 107 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99470	1.1274	93
99468	0.2328	60
99469	0.1118	46
99466	0.1003	48
205666	0.0358	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.37	gold quality
cerebellar hemisphere	UBERON:0002245	97.77	gold quality
cerebellar cortex	UBERON:0002129	97.55	gold quality
right frontal lobe	UBERON:0002810	96.72	gold quality
cerebellum	UBERON:0002037	94.82	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.59	gold quality
anterior cingulate cortex	UBERON:0009835	92.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.52	gold quality
gastrocnemius	UBERON:0001388	88.36	gold quality
putamen	UBERON:0001874	87.48	gold quality
muscle of leg	UBERON:0001383	87.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.91	gold quality
prefrontal cortex	UBERON:0000451	86.15	gold quality
caudate nucleus	UBERON:0001873	85.55	gold quality
spleen	UBERON:0002106	84.81	gold quality
neocortex	UBERON:0001950	84.69	gold quality
frontal cortex	UBERON:0001870	84.59	gold quality
nucleus accumbens	UBERON:0001882	83.35	gold quality
adenohypophysis	UBERON:0002196	82.95	gold quality
pituitary gland	UBERON:0000007	82.57	gold quality
hypothalamus	UBERON:0001898	82.46	gold quality
brain	UBERON:0000955	81.53	gold quality
amygdala	UBERON:0001876	81.42	gold quality
cerebral cortex	UBERON:0000956	81.05	gold quality
forebrain	UBERON:0001890	80.95	gold quality
left ovary	UBERON:0002119	79.42	gold quality
right ovary	UBERON:0002118	78.47	gold quality
adrenal tissue	UBERON:0018303	76.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.37	gold quality
apex of heart	UBERON:0002098	74.92	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting KCNT1, 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-6798-5P	100.00	65.77	699
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-647	97.73	67.79	927
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-4313	97.18	63.15	420
HSA-MIR-6836-3P	97.08	64.99	712
HSA-MIR-505-5P	97.01	65.54	778
HSA-MIR-1288-3P	96.86	66.95	536

Literature-anchored findings (GeneRIF, showing 32)

• Mutations in KCNT1 cause a severe form of ADNFLE and sporadic NFLE. (PMID:23086396)
• Our data identify KCNT1 as a major disease-associated gene in Malignant migrating partial seizures of infancy . (PMID:23086397)
• this study performed analysis of KCNT1 in two unrelated patients with malignant migrating partial seizures in infancy.Because the G-to-A transition was located at CG dinucleotide sequences as previously reported for KCNT1 mutations, the recurrent occurrence of de novo KCNT1 mutations indicated the hot spots of these locations. (PMID:24029078)
• This gene-wide tagging study revealed no association between KCNT1 17 common variations and susceptibility of GGEs or AEDs (anti-epileptic drugs) efficacy of genetic generalized epilepsies in Chinese population. (PMID:24279416)
• Novel variations in KCNT1 do not allow prediction of functional phenotypes that might explain, at least in part, the symptoms of malignant migrating partial seizures of infancy (MMPSI). (PMID:24315024)
• Genetic studies reveal two novel genes for Ohtahara Syndrome: KCNT1 and PIGQ. (PMID:24463883)
• This study demonistrated that KCNT1 mutations implicated in epilepsy cause a marked increase in function (PMID:24591078)
• Five de novo mutations were identified in four genes (SCNN1A, KCNJ16, KCNB2, and KCNT1) in three Brugada syndrome patients (20%) (PMID:25339316)
• Slick channels, in contrast to the similar Slack channels, are the only high-conductance K+ channels strongly sensitive to small changes in cell volume. (PMID:25347289)
• Nine different mutations of the KCNT1 (Slack) Na(+)-activated K(+) channel give rise to three distinct forms of epilepsy. (PMID:25482562)
• We demonstrate that KCNT1 mutations are highly pleiotropic and are associated with phenotypes other than nocturnal frontal lobe epilepsy and malignant migrating focal seizures of infancy. (PMID:26122718)
• This study demonstrate that KCNT1 mutations are strongly associated with early-onset epileptic encephalopathy. (PMID:26140313)
• The sodium sensitivity of these epilepsy causing mutants probably determines the [Na(+)]i concentration at which these mutants exert their pathological effects. (PMID:26725113)
• Better understanding of the mechanisms underlying KCNT1-related disease will produce further improvements in treatment of the associated severe seizure disorders. (PMID:26740507)
• two de novo, heterozygous KCNT1 mutations were identified in two unrelated malignant migrating partial seizures probands. Both mutations induced a marked leftward shift in homomeric channel activation gating. (PMID:26784557)
• Stimulation of Slack K(+) channels alters mass at the plasma membrane by triggering dissociation of Phactr-1. (PMID:27545877)
• In the present study, we evaluated two other potential mechanisms for stabilization of Slo2 channels in a closed state: (1) dewetting and collapse of the inner pore (hydrophobic gating) and (2) constriction of the inner pore by tight criss-crossing of the cytoplasmic ends of the S6 alpha-helical segments. (PMID:27682982)
• G288S missense mutation, associated with seizures and neurodevelopmental delay resulted in larger whole cell K+ currents compared with wild-type KCNT1 currents. (PMID:28747464)
• Case report describing 3 infants with malignant migrating partial seizures with KCNT1 mutations accompanied by massive systemic to pulmonary collateral arteries. (PMID:28987752)
• Gain-of-function KCNT1 pathogenic variants cause a spectrum of severe focal epilepsies with onset in early infancy. Computational modeling analysis implicates abnormal pore function (F346L) and impaired tetramer formation (F502V) as putative disease mechanisms. All evaluated KCNT1 variants resulted in marked gain of function with significantly increased channel amplitude and variable blockade by quinidine. (PMID:29196579)
• studied the mutational characteristics of KCNT1 and its clinical features in children with early-onset epileptic encephalopathy;the mutation of KCNT1 gene is mainly de novo. The onset of the disease was early, and mostly occurs in neonate and early infancy (PMID:30392206)
• that KCNT1 epileptogenicity may result not only from dysregulated excitability by controlling Na+K+ transport (PMID:30847371)
• KCNT1 mutations lead to a severe form of epilepsy; this KCNT1 mutation was found to increase the Slack current in neurons. (PMID:31350261)
• Extracerebral symptoms probably linked with KCNT1 mutation were present, including arteriovenous fistula, dilated cardiomyopathy and precocious puberty. Eight patients (47%) had died at 3 (1.5-15.4) years including three from suspected sudden unexpected death in epilepsy. (PMID:31532509)
• KCNT1 is likely to be a major gene causing early infantile epileptic encephalopathy type 14 (PMID:31532594)
• Recurrent pulmonary hemorrhage in juvenile patients with KCNT1 mutation. (PMID:33650128)
• KCNT1-related epilepsies and epileptic encephalopathies: phenotypic and mutational spectrum. (PMID:34114611)
• The phenotypic spectrum of KCNT1: a new family with variable epilepsy syndromes including mild focal epilepsy. (PMID:34537872)
• Functional Effects of Epilepsy Associated KCNT1 Mutations Suggest Pathogenesis via Aberrant Inhibitory Neuronal Activity. (PMID:36499459)
• Functional evaluation of epilepsy-associated KCNT1 variants in multiple cellular systems reveals a predominant gain of function impact on channel properties. (PMID:37177976)
• Coupling of Slack and NaV1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development. (PMID:38289338)
• A molecular switch in RCK2 triggers sodium-dependent activation of KNa1.1 (KCNT1) potassium channels. (PMID:38605520)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnt1a	ENSDARG00000079484
danio_rerio	kcnt1b	ENSDARG00000104868
mus_musculus	Kcnt1	ENSMUSG00000058740
rattus_norvegicus	Kcnt1	ENSRNOG00000017283
drosophila_melanogaster	SLO2	FBGN0261698
caenorhabditis_elegans		WBGENE00004831

Paralogs (3): KCNMA1 (ENSG00000156113), KCNT2 (ENSG00000162687), KCNU1 (ENSG00000215262)

Protein

Protein identifiers

Potassium channel subfamily T member 1 — Q5JUK3 (reviewed: Q5JUK3)

Alternative names: KCa4.1, KNa1.1, Sodium and chloride-activated ATP-sensitive potassium channel Slo2.2

All UniProt accessions (14): Q5JUK3, A0A0D9SEY3, A0A0D9SFC8, A0A0D9SFR1, A0A0R4J2E0, A0A6Q8PFE8, A0A6Q8PFI9, A0A6Q8PFS3, A0A6Q8PGM3, C9J9Y7, C9JAX7, C9JBV2, C9JYL2, F8WC49

UniProt curated annotations — full annotation on UniProt →

Function. Sodium-activated K(+) channel. Acts as an important mediator of neuronal membrane excitability. Contributes to the delayed outward currents. Regulates neuronal bursting in sensory neurons. Contributes to synaptic development and plasticity.

Subunit / interactions. Homotetramer; which constitutes the Na(+)-activated K(+) channel. Interacts with KCNT2; these heterodimer channels differ from the homomers in their unitary conductance, kinetic behavior, subcellular localization, and response to activation of protein kinase C. Interacts (via C-terminus) with FMR1; this interaction alters gating properties of KCNT1. Interacts with CRBN via its cytoplasmic C-terminus.

Subcellular location. Cell membrane.

Tissue specificity. Highest expression in liver, brain and spinal cord. Lowest expression in skeletal muscle.

Post-translational modifications. Phosphorylated by protein kinase C. Phosphorylation of the C-terminal domain increases channel activity.

Disease relevance. Developmental and epileptic encephalopathy 14 (DEE14) [MIM:614959] A rare epileptic encephalopathy of infancy that combines pharmacoresistant seizures with developmental delay. This severe neurologic disorder is characterized by onset in the first 6 months of life of refractory focal seizures and arrest of psychomotor development. Ictal EEG shows discharges that arise randomly from various areas of both hemispheres and migrate from one brain region to another. The disease is caused by variants affecting the gene represented in this entry. Epilepsy, nocturnal frontal lobe, 5 (ENFL5) [MIM:615005] An autosomal dominant focal epilepsy syndrome characterized by childhood onset of clusters of motor seizures during sleep. Some patients may develop behavioral or psychiatric manifestations and/or intellectual disability. The phenotype is more severe than observed in other genetic forms of nocturnal frontal lobe epilepsy. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by high intracellular Na(+). In addition to activation by Na(+), is cooperatively activated by intracellular Cl(-) levels. Inhibited by Zn(2+). Activated upon stimulation of G-protein coupled receptors, such as CHRM1 and GRIA1.

Domain organisation. The cytoplasmic gating ring domain of the closed KCNT1 channel harbors multiple K(+) and Zn(2+) sites, which stabilize the channel in the closed conformation. Under low-Na(+) conditions, the abundant cytoplasmic K(+) ions stabilize the gating ring domain in a closed conformation. KCNT1 contains at least two Na(+)-sensitive sites in the RCKs domain where Na(+) binding induces expansion and rotation of the gating ring that opens the inner gate. The cytoplasmic N-terminal domain facilitates the localization of heteromeric KCNT1/KCNT2 channels to the plasma membrane.

Similarity. Belongs to the potassium channel family. Calcium-activated (TC 1.A.1.3) subfamily. KCa4.1/KCNT1 sub-subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5JUK3-1	1	yes
Q5JUK3-2	2
Q5JUK3-3	3
Q5JUK3-4	4

RefSeq proteins (2): NP_001258932, NP_065873* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003148	RCK_N	Domain
IPR003929	K_chnl_BK_asu	Domain
IPR013099	K_chnl_dom	Domain
IPR047871	K_chnl_Slo-like	Family

Pfam: PF03493, PF07885, PF22614

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (170 total): helix 48, strand 30, binding site 25, sequence variant 15, mutagenesis site 10, topological domain 8, transmembrane region 6, turn 6, splice variant 5, sequence conflict 5, region of interest 4, domain 2, compositionally biased region 2, glycosylation site 2, chain 1, intramembrane region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8HK6	ELECTRON MICROSCOPY	2.64
8HKF	ELECTRON MICROSCOPY	2.66
8HKK	ELECTRON MICROSCOPY	2.84
8HKQ	ELECTRON MICROSCOPY	2.9
8HKM	ELECTRON MICROSCOPY	2.95
8HIR	ELECTRON MICROSCOPY	3.18

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JUK3-F1	74.94	0.36

Functional residue map

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

Ligand- & substrate-binding residues (25): 296; 297; 513; 516; 538; 540; 758; 759; 761; 761; 764; 764 …

Glycosylation sites (2): 133, 137

Mutagenesis-validated functional residues (10):

Position	Phenotype
315	reduced the potency of the agonist c23 by 7-8 fold.
319	reduced the potency of the agonist c23 by 7-8 fold.
327	reduced the potency of the agonist c23 by 28 fold.
541	dramatically reduced the na(+) sensitivity of kcnt1.
758–759	decreased inhibition by zn(2+).
769	reduced the na(+) sensitivity of kcnt1.
777	reduced the na(+) sensitivity of kcnt1.
820	dramatically reduced the na(+) sensitivity of kcnt1.
865	dramatically reduced the na(+) sensitivity of kcnt1.
873–876	dramatically reduced the na(+) sensitivity of kcnt1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 189 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_PROTEIN_HOMOTETRAMERIZATION, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_PROTEIN_TETRAMERIZATION, GOBP_TRANSMEMBRANE_TRANSPORT, LEIN_CEREBELLUM_MARKERS, GOMF_VOLTAGE_GATED_MONOATOMIC_CATION_CHANNEL_ACTIVITY, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_GATED_CHANNEL_ACTIVITY, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_VOLTAGE_GATED_POTASSIUM_CHANNEL_ACTIVITY, YOSHIMURA_MAPK8_TARGETS_UP

GO Biological Process (5): protein homotetramerization (GO:0051289), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (4): intracellular sodium-activated potassium channel activity (GO:0005228), outward rectifier potassium channel activity (GO:0015271), metal ion binding (GO:0046872), potassium channel activity (GO:0005267)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein homooligomerization	1
protein tetramerization	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
potassium channel activity	1
monoatomic ion-gated channel activity	1
ligand-gated monoatomic cation channel activity	1
voltage-gated potassium channel activity	1
cation binding	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNT1	KCNQ2	O43526	768
KCNT1	SCN1A	P35498	735
KCNT1	SCN2A	Q99250	717
KCNT1	DEPDC5	O75140	696
KCNT1	STXBP1	P61764	674
KCNT1	SCN8A	Q9UQD0	672
KCNT1	CHRNB2	P17787	669
KCNT1	CHRNA2	Q15822	669
KCNT1	CDKL5	O76039	667
KCNT1	PCDH19	Q8TAB3	654
KCNT1	CHRNA4	P43681	638
KCNT1	KCNQ3	O43525	635
KCNT1	SLC25A22	Q9H936	629
KCNT1	TBC1D24	Q9ULP9	620
KCNT1	FMR1	Q06787	615

IntAct

117 interactions, top by confidence:

A	B	Type	Score
KCNT1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
PDZRN3	KCNT1	psi-mi:“MI:0407”(direct interaction)	0.440
RHPN1	KCNT1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
SNTG2	KCNT1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	KCNT1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNT1	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (1): KCNT1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A2R8QFQ6, A0A2R8RWN9, A0JN27, D3Z7P3, F1LTR1, O15294, O60907, O89050, O94925, P13264, P56558, P81436, Q07G17, Q13042, Q13888, Q15303, Q27HV0, Q28D01, Q2TBV5, Q3ULA2, Q4R8H1, Q4R9A8, Q4VC33, Q5F398, Q5JUK3, Q5R532, Q5RB35, Q5RKJ1, Q5SP67, Q5SRY7, Q61527, Q62956, Q6GR10, Q6P1K8, Q7L5Y9, Q7RTP6, Q7SXR3, Q8C6G8, Q8CGY8, Q8CJ19

Diamond homologs: D3Z649, Q57603, Q5JUK3, Q69TN4, Q6UVM3, Q6UVM4, Q6ZPR4, Q850M0, Q8LBL1, Q8QFV0, Q9FWX6, Q9Z258, A2BDX4, D4AD53, O73606, P31069, Q52PG9, Q80XM3, Q8LIN5, Q8TDN1, Q95V25, Q9NSA2, Q9UIX4, Q9XXD1, A0A509AS68, A5LFX5, A8MYU2, D4A6Z8, O17185, O35174, O43526, O54982, O88943, P56696, Q57604, Q8I5E6, Q8IKI3, Q92953, Q979Z2, Q9ER26

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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
Ras activation upon Ca2+ influx through NMDA receptor	5	58.3×	8e-07
Unblocking of NMDA receptors, glutamate binding and activation	5	55.5×	8e-07
Negative regulation of NMDA receptor-mediated neuronal transmission	5	55.5×	8e-07
Long-term potentiation	5	48.5×	1e-06
Assembly and cell surface presentation of NMDA receptors	9	46.6×	2e-11
Neurexins and neuroligins	10	40.2×	7e-12
Protein-protein interactions at synapses	6	32.5×	8e-07
RHOB GTPase cycle	5	15.8×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	79.6×	1e-14
protein localization to synapse	6	63.0×	4e-08
receptor clustering	7	59.9×	4e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	47.5×	2e-08
cell-cell adhesion	10	13.9×	2e-07
protein-containing complex assembly	7	10.9×	2e-04
regulation of small GTPase mediated signal transduction	5	9.9×	4e-03
protein localization to plasma membrane	5	7.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2592 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	35
Uncertain significance	998
Likely benign	1105
Benign	151

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
126421	NM_020822.3(KCNT1):c.862G>A (p.Gly288Ser)	Pathogenic
1401332	NM_020822.3(KCNT1):c.2012C>T (p.Thr671Ile)	Pathogenic
1457517	NM_020822.3(KCNT1):c.2687T>A (p.Met896Lys)	Pathogenic
1457519	NM_020822.3(KCNT1):c.2797C>G (p.Arg933Gly)	Pathogenic
183028	NM_020822.3(KCNT1):c.2688G>A (p.Met896Ile)	Pathogenic
2110314	NM_020822.3(KCNT1):c.2801C>T (p.Ala934Val)	Pathogenic
265210	NM_020822.3(KCNT1):c.1420C>T (p.Arg474Cys)	Pathogenic
265211	NM_020822.3(KCNT1):c.1426T>C (p.Trp476Arg)	Pathogenic
2925457	NM_020822.3(KCNT1):c.2771C>T (p.Pro924Leu)	Pathogenic
3756577	NM_020822.3(KCNT1):c.785G>C (p.Arg262Pro)	Pathogenic
3776340	NM_020822.3(KCNT1):c.820C>A (p.Leu274Ile)	Pathogenic
379933	NM_020822.3(KCNT1):c.2688G>C (p.Met896Ile)	Pathogenic
3901166	NM_020822.3(KCNT1):c.2688G>T (p.Met896Ile)	Pathogenic
39593	NM_020822.3(KCNT1):c.1283G>A (p.Arg428Gln)	Pathogenic
39594	NM_020822.3(KCNT1):c.2800G>A (p.Ala934Thr)	Pathogenic
39596	NM_020822.3(KCNT1):c.2280C>G (p.Ile760Met)	Pathogenic
39597	NM_020822.3(KCNT1):c.2782C>T (p.Arg928Cys)	Pathogenic
412308	NM_020822.3(KCNT1):c.2687T>G (p.Met896Arg)	Pathogenic
445339	NM_020822.3(KCNT1):c.808C>G (p.Gln270Glu)	Pathogenic
4686266	NM_020822.3(KCNT1):c.554TAA[1] (p.Ile186del)	Pathogenic
473378	NM_020822.3(KCNT1):c.2849G>T (p.Arg950Leu)	Pathogenic
655949	NM_020822.3(KCNT1):c.2717A>G (p.Gln906Arg)	Pathogenic
813716	GRCh37/hg19 9q34.3(chr9:138225001-141015001)	Pathogenic
853172	NM_020822.3(KCNT1):c.2943+1G>C	Pathogenic
853550	NM_020822.3(KCNT1):c.1038C>G (p.Phe346Leu)	Pathogenic
871329	NM_020822.3(KCNT1):c.811G>T (p.Val271Phe)	Pathogenic
92165	NM_020822.3(KCNT1):c.2794T>A (p.Phe932Ile)	Pathogenic
999973	NM_020822.3(KCNT1):c.1136G>A (p.Ser379Asn)	Pathogenic
1320152	NM_020822.3(KCNT1):c.1406A>C (p.His469Pro)	Likely pathogenic
1328519	NM_020822.3(KCNT1):c.3001A>T (p.Thr1001Ser)	Likely pathogenic

SpliceAI

6165 predictions. Top by Δscore:

Variant	Effect	Δscore
9:135714717:ACAGG:A	donor_loss	1.0000
9:135714718:CAGGT:C	donor_loss	1.0000
9:135714719:AGG:A	donor_loss	1.0000
9:135714720:GGT:G	donor_loss	1.0000
9:135714721:GT:G	donor_loss	1.0000
9:135714722:T:A	donor_loss	1.0000
9:135750176:GA:G	donor_gain	1.0000
9:135750178:G:GG	donor_gain	1.0000
9:135756863:T:A	acceptor_gain	1.0000
9:135756931:AA:A	donor_gain	1.0000
9:135756932:AG:A	donor_loss	1.0000
9:135756933:G:GG	donor_gain	1.0000
9:135757151:CCCA:C	acceptor_loss	1.0000
9:135757152:CCAG:C	acceptor_loss	1.0000
9:135757153:CAG:C	acceptor_loss	1.0000
9:135757154:A:AG	acceptor_gain	1.0000
9:135757155:G:GA	acceptor_loss	1.0000
9:135757155:G:GG	acceptor_gain	1.0000
9:135757377:TGATT:T	donor_gain	1.0000
9:135757378:GATT:G	donor_gain	1.0000
9:135757378:GATTG:G	donor_gain	1.0000
9:135757380:TT:T	donor_gain	1.0000
9:135757382:G:GG	donor_gain	1.0000
9:135758409:CACA:C	acceptor_loss	1.0000
9:135758410:ACAG:A	acceptor_loss	1.0000
9:135758411:CA:C	acceptor_loss	1.0000
9:135758412:A:AG	acceptor_gain	1.0000
9:135758412:AG:A	acceptor_loss	1.0000
9:135758412:AGAAT:A	acceptor_gain	1.0000
9:135758413:G:GT	acceptor_gain	1.0000

AlphaMissense

8127 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:135765164:T:C	L371P	1.000
9:135765696:T:A	W406R	1.000
9:135765696:T:C	W406R	1.000
9:135765748:T:C	L423P	1.000
9:135768845:T:C	L454P	1.000
9:135768853:T:A	W457R	1.000
9:135768853:T:C	W457R	1.000
9:135768931:T:C	F483L	1.000
9:135768933:T:A	F483L	1.000
9:135768933:T:G	F483L	1.000
9:135777402:T:A	V786D	1.000
9:135779391:T:C	L902P	1.000
9:135779414:T:C	F910L	1.000
9:135779415:T:C	F910S	1.000
9:135779416:C:A	F910L	1.000
9:135779416:C:G	F910L	1.000
9:135779423:T:C	F913L	1.000
9:135779424:T:C	F913S	1.000
9:135779425:C:A	F913L	1.000
9:135779425:C:G	F913L	1.000
9:135784060:T:C	F941L	1.000
9:135784062:C:A	F941L	1.000
9:135784062:C:G	F941L	1.000
9:135784076:C:A	A946D	1.000
9:135757349:T:A	W224R	0.999
9:135757349:T:C	W224R	0.999
9:135759770:G:C	G297R	0.999
9:135759849:T:A	L323H	0.999
9:135765122:T:C	L357P	0.999
9:135765637:T:A	V386D	0.999

dbSNP variants (sampled 300 via entrez): RS1000005694 (9:135737841 C>T), RS1000020770 (9:135772522 G>A), RS1000074559 (9:135772286 G>A), RS1000075323 (9:135736028 G>A), RS1000076050 (9:135765893 G>A,T), RS1000080457 (9:135740895 GCTCCCCTCCC>G,GCTCCC,GCTCCCCTCCCCTCCC), RS1000092965 (9:135724798 T>C), RS1000109740 (9:135707790 C>T), RS1000159725 (9:135752769 G>A), RS1000169689 (9:135762724 T>G), RS1000224165 (9:135755382 G>A), RS1000236784 (9:135732370 C>A,T), RS1000273619 (9:135721551 G>A), RS1000325169 (9:135768472 C>G,T), RS1000353255 (9:135736270 C>G,T)

Disease associations

OMIM: gene MIM:608167 | disease phenotypes: MIM:614959, MIM:615005, MIM:619561, MIM:616028, MIM:130000, MIM:181500, MIM:117100, MIM:615006, MIM:600513, MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 14	Definitive	Autosomal dominant
malignant migrating partial seizures of infancy	Definitive	Autosomal dominant
autosomal dominant nocturnal frontal lobe epilepsy 5	Strong	Autosomal dominant
autosomal dominant nocturnal frontal lobe epilepsy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
childhood-onset epilepsy syndrome	Definitive	AD

Mondo (23): developmental and epileptic encephalopathy, 14 (MONDO:0013989), autosomal dominant nocturnal frontal lobe epilepsy 5 (MONDO:0014002), epilepsy (MONDO:0005027), focal epilepsy (MONDO:0005384), developmental and epileptic encephalopathy 97 (MONDO:0030453), Adams-Oliver syndrome 5 (MONDO:0014459), Ehlers-Danlos syndrome, classic type, 1 (MONDO:0019567), intellectual disability (MONDO:0001071), hearing loss disorder (MONDO:0005365), neurodevelopmental disorder (MONDO:0700092), schizophrenia (MONDO:0005090), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), breast ductal adenocarcinoma (MONDO:0005590), malignant migrating partial seizures of infancy (MONDO:0017385), developmental and epileptic encephalopathy, 15 (MONDO:0014003)

Orphanet (11): Epilepsy of infancy with migrating focal seizures (Orphanet:293181), Sleep-related hypermotor epilepsy (Orphanet:98784), Adams-Oliver syndrome (Orphanet:974), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), West syndrome (Orphanet:3451), Epilepsy syndrome (Orphanet:166463), Childhood-onset epilepsy syndrome (Orphanet:98259), Renal or urinary tract malformation (Orphanet:93545), OBSOLETE: Ehlers-Danlos syndrome type 1 (Orphanet:90309), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

82 total (30 of 82 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000252	Microcephaly
HP:0000505	Visual impairment
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000733	Motor stereotypy
HP:0000739	Anxiety
HP:0000817	Reduced eye contact
HP:0000826	Precocious puberty
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001273	Abnormal corpus callosum morphology
HP:0001276	Hypertonia
HP:0001290	Generalized hypotonia
HP:0001344	Absent speech
HP:0001345	Psychotic mentation
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure
HP:0002079	Hypoplasia of the corpus callosum
HP:0002120	Cerebral cortical atrophy
HP:0002133	Status epilepticus
HP:0002169	Clonus
HP:0002171	Gliosis

GWAS associations

0 associations (top):

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D002493	Central Nervous System Diseases	C10.228
D004828	Epilepsies, Partial	C10.228.140.490.360
D004827	Epilepsy	C10.228.140.490
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D006849	Hydrocephalus	C10.228.140.602
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
C566906	Cakut (supp.)
C536194	Ehlers-Danlos syndrome type 1 (supp.)
C563930	Epilepsy, Nocturnal Frontal Lobe, Type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4739688 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 83,719 (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
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1294	QUINIDINE	4	71,943

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

PharmGKB variants

17 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs487750	KCNT1		0.00	0
rs496503	KCNT1		0.00	0
rs498618	KCNT1		0.00	0
rs498974	KCNT1		0.00	0
rs546120	KCNT1, SOHLH1		0.00	0
rs755722	KCNT1		0.00	0
rs1165016	KCNT1		0.00	0
rs1318383	KCNT1		0.00	0
rs1537416	KCNT1		0.00	0
rs7855716	KCNT1		0.00	0
rs10118746	KCNT1		0.00	0
rs10735239	KCNT1		0.00	0
rs10776845	KCNT1		0.00	0
rs10776850	KCNT1		0.00	0
rs10858173	KCNT1		0.00	0
rs11103167	KCNT1		0.00	0
rs11103182	KCNT1		0.00	0

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 (10 total), top 10:

Ligand	Action	Affinity	Parameter
PRX-2904	Channel blocker	7.4	pIC50
phorbol 12-myristate 13-acetate	Agonist	7.3	pEC50
CPK20	Channel blocker	6.7	pIC50
Ca2+	Antagonist	6.5	pIC50
VU0948578	Channel blocker	6.15	pIC50
bepridil	Gating inhibitor	6.0	pIC50
bithionol	Agonist	6.0	pEC50
niclosamide	Agonist	5.54	pEC50
loxapine	Agonist	5.36	pEC50
tetraethylammonium	Antagonist	2.0	pIC50

ChEMBL bioactivities

72 potent at pChembl≥5 of 80 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.80	IC50	16	nM	CHEMBL4763955
7.57	IC50	27	nM	CHEMBL4788669
7.40	IC50	40	nM	CHEMBL4741793
7.21	IC50	61	nM	CHEMBL4754084
7.10	IC50	80	nM	CHEMBL5558979
6.87	IC50	136	nM	CHEMBL4783741
6.78	IC50	167	nM	CHEMBL4793291
6.78	IC50	165	nM	CHEMBL4786255
6.71	IC50	195	nM	CHEMBL4793279
6.70	IC50	200	nM	CHEMBL2398613
6.68	IC50	210	nM	CHEMBL4476393
6.49	IC50	322	nM	CHEMBL4750925
6.47	IC50	335	nM	CHEMBL4783466
6.34	IC50	454	nM	CHEMBL4795194
6.30	IC50	505	nM	CHEMBL4743249
6.24	IC50	573	nM	CHEMBL4781553
6.13	IC50	744	nM	CHEMBL4745211
6.11	IC50	778	nM	CHEMBL4758890
6.01	IC50	977	nM	CHEMBL4779088
5.96	IC50	1100	nM	CHEMBL5220335
5.86	IC50	1373	nM	CHEMBL4750826
5.85	IC50	1410	nM	CHEMBL4744857
5.85	IC50	1400	nM	CHEMBL5218475
5.80	IC50	1597	nM	CHEMBL4789512
5.77	IC50	1700	nM	CHEMBL1730394
5.77	IC50	1700	nM	CHEMBL5221076
5.74	IC50	1840	nM	CHEMBL1730394
5.73	IC50	1876	nM	CHEMBL4750807
5.72	IC50	1900	nM	CHEMBL5219802
5.72	IC50	1910	nM	CHEMBL6167939
5.64	IC50	2300	nM	CHEMBL5219391
5.64	IC50	2300	nM	CHEMBL5220721
5.62	IC50	2400	nM	CHEMBL1730394
5.62	IC50	2400	nM	CHEMBL5220721
5.62	IC50	2400	nM	CHEMBL5221076
5.58	IC50	2642	nM	CHEMBL4740667
5.52	IC50	3000	nM	CHEMBL5219121
5.50	IC50	3200	nM	CHEMBL5218502
5.48	IC50	3314	nM	CHEMBL4763819
5.47	IC50	3400	nM	CHEMBL5219802
5.47	IC50	3400	nM	CHEMBL5558979
5.46	IC50	3500	nM	CHEMBL5220924
5.46	IC50	3500	nM	CHEMBL5220256
5.46	IC50	3430	nM	CHEMBL6163029
5.42	EC50	3800	nM	CHEMBL5220290
5.39	EC50	4100	nM	CHEMBL5219384
5.37	IC50	4300	nM	CHEMBL5220498
5.37	IC50	4250	nM	CHEMBL6145188
5.36	IC50	4400	nM	CHEMBL5221061
5.35	IC50	4466	nM	CHEMBL4777757

PubChem BioAssay actives

65 with measured affinity, of 176 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
N-[(1S)-1-[3-(2-cyclopropyl-4-pyridinyl)-1,2,4-oxadiazol-5-yl]ethyl]-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.0160	uM
N-[(1S)-1-[3-(2-methoxy-4-pyridinyl)-1,2,4-oxadiazol-5-yl]ethyl]-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.0270	uM
1-methyl-3-(trifluoromethyl)-N-[(1S)-1-[3-[2-(trifluoromethyl)-4-pyridinyl]-1,2,4-oxadiazol-5-yl]ethyl]pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.0400	uM
N-[(1S)-1-[3-[2-(difluoromethyl)-4-pyridinyl]-1,2,4-oxadiazol-5-yl]ethyl]-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.0610	uM
(2S)-N-benzyl-3-(1H-indol-3-yl)-2-[(4-phenoxyphenyl)methylamino]propanamide	2077328: Inhibition of human KCNT1 (98 to 354 residues) expressed in CHO cells at +60 mV holding potential by whole-cell patch clamp electrophysiology method	ic50	0.0800	uM
N-[(1S)-1-[3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl]ethyl]-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.1360	uM
1-methyl-N-[(1S)-1-[3-(2-methyl-4-pyridinyl)-1,2,4-oxadiazol-5-yl]ethyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.1650	uM
3-cyclopropyl-1-methyl-N-[(1S)-1-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]ethyl]pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.1670	uM
1-methyl-N-[(1S)-1-[3-[2-(methylamino)-4-pyridinyl]-1,2,4-oxadiazol-5-yl]ethyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.1950	uM
ethyl (2S,4R)-5’-bromo-3-(4-chlorobenzoyl)-2’-oxospiro[1,3-thiazolidine-2,3’-1H-indole]-4-carboxylate	2077328: Inhibition of human KCNT1 (98 to 354 residues) expressed in CHO cells at +60 mV holding potential by whole-cell patch clamp electrophysiology method	ic50	0.2000	uM
N-[1-[[2,4-bis(trifluoromethyl)phenyl]methyl]-2,3-dihydroindol-5-yl]cyclohexanesulfonamide	2077328: Inhibition of human KCNT1 (98 to 354 residues) expressed in CHO cells at +60 mV holding potential by whole-cell patch clamp electrophysiology method	ic50	0.2100	uM
N-[(1S)-1-[3-[2-(methoxymethyl)-4-pyridinyl]-1,2,4-oxadiazol-5-yl]ethyl]-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.3220	uM
3-ethyl-1-methyl-N-[(1S)-1-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]ethyl]pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.3350	uM
N-[(1S)-1-[3-[2-(dimethylamino)-4-pyridinyl]-1,2,4-oxadiazol-5-yl]ethyl]-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.4540	uM
N-[(1S)-1-[3-(2-methoxy-6-methyl-4-pyridinyl)-1,2,4-oxadiazol-5-yl]ethyl]-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.5050	uM
1-methyl-N-[(1S)-1-[3-(2-pyrrolidin-1-yl-4-pyridinyl)-1,2,4-oxadiazol-5-yl]ethyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.5730	uM
N-[(1S)-1-[3-[2-[(1S)-1-methoxyethyl]-4-pyridinyl]-1,2,4-oxadiazol-5-yl]ethyl]-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.7440	uM
N-[(1S)-1-[3-[2-[(1R)-1-methoxyethyl]-4-pyridinyl]-1,2,4-oxadiazol-5-yl]ethyl]-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.7780	uM
1-methyl-N-[1-[5-(3-methylphenyl)-1,2,4-oxadiazol-3-yl]ethyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	0.9770	uM
2-[4-[4-(benzenesulfonyl)piperazin-1-yl]sulfonylpiperazin-1-yl]-N-(5-chloro-2-methoxyphenyl)acetamide	1917572: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ic50	1.1000	uM
1-methyl-N-[(1S)-1-[3-(5-methyl-3-pyridinyl)-1,2,4-oxadiazol-5-yl]ethyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	1.3730	uM
N-(5-bromo-2-methoxyphenyl)-2-[4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]acetamide	1917572: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ic50	1.4000	uM
1-methyl-N-[(1S)-1-[3-(6-methylpyrimidin-4-yl)-1,2,4-oxadiazol-5-yl]ethyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	1.4100	uM
1-methyl-N-[1-[1-(3-methylphenyl)pyrazol-4-yl]ethyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	1.5970	uM
N-(5-chloro-2-methoxyphenyl)-2-[(2R)-2-methyl-4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]acetamide	1917583: Inhibition of wild-type Slack (unknown origin) expressed in HEK293 cells measured by whole-cell electrophysiology assay	ic50	1.7000	uM
N-(5-chloro-2-methoxyphenyl)-2-[4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]acetamide	1917583: Inhibition of wild-type Slack (unknown origin) expressed in HEK293 cells measured by whole-cell electrophysiology assay	ic50	1.7000	uM
3-cyclopropyl-1-methyl-N-[1-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]ethyl]pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	1.8760	uM
(2S)-N-(5-chloro-2-methoxyphenyl)-2-[4-[4-(trifluoromethyl)piperidin-1-yl]sulfonylpiperazin-1-yl]propanamide	1917583: Inhibition of wild-type Slack (unknown origin) expressed in HEK293 cells measured by whole-cell electrophysiology assay	ic50	1.9000	uM
N-(5-chloro-2-methoxyphenyl)-2-[4-[4-(4-chlorophenyl)sulfonylpiperazin-1-yl]sulfonylpiperazin-1-yl]acetamide	1917572: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ic50	2.3000	uM
N-[2-methoxy-5-(trifluoromethyl)phenyl]-2-[4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]acetamide	1917583: Inhibition of wild-type Slack (unknown origin) expressed in HEK293 cells measured by whole-cell electrophysiology assay	ic50	2.3000	uM
1-methyl-N-[(1S)-1-[3-(1-methylpyrazol-4-yl)-1,2,4-oxadiazol-5-yl]ethyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	2.6420	uM
2-(1,3-dioxoisoindol-2-yl)-N-[3-(trifluoromethyl)phenyl]-1,3-benzothiazole-6-carboxamide	1917570: Inhibition of wild-type human Slack expressed in HEK293 cells measured by whole-cell patch clamp assay	ic50	3.0000	uM
3-[4-[[2-(3-methylphenyl)acetyl]amino]pyrazol-1-yl]-N-[[2-(1,2,4-triazol-1-yl)phenyl]methyl]benzamide	1917570: Inhibition of wild-type human Slack expressed in HEK293 cells measured by whole-cell patch clamp assay	ic50	3.2000	uM
3-cyclopropyl-1-methyl-N-[(1R)-1-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]ethyl]pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	3.3140	uM
N-(5-chloro-2-methoxyphenyl)-2-[(2S)-2-methyl-4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]acetamide	1917572: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ic50	3.5000	uM
(2R)-N-(5-chloro-2-methoxyphenyl)-2-[4-[4-(trifluoromethyl)piperidin-1-yl]sulfonylpiperazin-1-yl]propanamide	1917572: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ic50	3.5000	uM
N-(5-chloro-2-fluorophenyl)-2-[4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]acetamide	1917574: Activation of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ec50	3.8000	uM
N-(4-methylphenyl)-2-[4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]acetamide	1917574: Activation of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ec50	4.1000	uM
N-(5-chloro-2-propoxyphenyl)-2-[4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]acetamide	1917572: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ic50	4.3000	uM
(2S)-N-(5-chloro-2-methoxyphenyl)-2-[4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]propanamide	1917572: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ic50	4.4000	uM
1-methyl-N-[(1S)-1-[3-(4-methyl-2-pyridinyl)-1,2,4-oxadiazol-5-yl]ethyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	4.4660	uM
N-(3-fluorophenyl)-2-[4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]acetamide	1917574: Activation of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ec50	4.6000	uM
N-(5-fluoro-2-methoxyphenyl)-2-[4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]acetamide	1917572: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ic50	4.9000	uM
(2R)-N-(5-chloro-2-methoxyphenyl)-2-[4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]propanamide	1917572: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ic50	4.9000	uM
N-(5-chloro-2-propan-2-yloxyphenyl)-2-[4-(4-methylpiperidin-1-yl)sulfonylpiperazin-1-yl]acetamide	1917572: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ic50	5.1000	uM
1-methyl-N-[(1S)-1-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)ethyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	5.2450	uM
1-(2,2-dimethylpropyl)-3-[1-[(4-fluorophenyl)methyl]-2,3-dihydroindol-5-yl]urea	2077316: Inhibition of human KCNT1 (98 to 354 residues) expressed in CHO cells assessed as reduction in thallium fluorescent signal incubated for 15 mins followed by LOX addition measured after 15 mins by FluxOR green dye based fluorescence analysis	ic50	5.5000	uM
N-(5-chloro-2-methoxyphenyl)-4-(4-methylpiperidin-1-yl)sulfonyl-1,4-diazepane-1-carboxamide	1917572: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay	ic50	6.2000	uM
N-[(1S)-1-[3-[2-(2-methoxypropan-2-yl)-4-pyridinyl]-1,2,4-oxadiazol-5-yl]ethyl]-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	6.2820	uM
N-[(1S)-1-[3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl]ethyl]-N,1-dimethyl-3-(trifluoromethyl)pyrazole-5-carboxamide	1709654: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	ic50	6.4890	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
benzo(e)pyrene	increases methylation	1
beta-methylcholine	affects expression	1
2-palmitoylglycerol	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Catechin	affects cotreatment, decreases expression	1
Copper	affects cotreatment, decreases expression	1
Folic Acid	decreases expression	1
Hydrogen Peroxide	affects expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

24 unique, capped per target: 24 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4714778	Binding	Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay	Discovery of the First Orally Available, Selective K1.1 Inhibitor: In Vitro and In Vivo Activity of an Oxadiazole Series. — ACS Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B5RS	SHCDNi006-A	Induced pluripotent stem cell	Female
CVCL_E3WT	FINi102-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy