Developmental and epileptic encephalopathy, 14

Summary

Developmental and epileptic encephalopathy, 14 (MONDO:0013989) is a disease caused by KCNT1 (GenCC Definitive), with 7 cohort genes and 3 clinical trials. Top therapeutic interventions include esomeprazole.

At a glance

• Causal gene: KCNT1 (GenCC Definitive)
• Cohort genes: 7
• ClinVar variants: 2,188
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 14
Mondo ID	MONDO:0013989
OMIM	614959
DOID	DOID:0080439
UMLS	C3554195
MedGen	767109
GARD	0015886
Is cancer (heuristic)	no

Also known as: DEE14 · developmental and epileptic encephalopathy 14 · early infantile epileptic encephalopathy caused by mutation in KCNT1 · EIEE14 · epileptic encephalopathy, early infantile, 14 · epileptic encephalopathy, early infantile, type 14 · KCNT1 early infantile epileptic encephalopathy · KCNT1-related epilepsy

Data availability: 2,188 ClinVar variants · 4 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › Mendelian neurodevelopmental disorder › genetic developmental and epileptic encephalopathy › developmental and epileptic encephalopathy, 14

Related subtypes (104): developmental and epileptic encephalopathy, 9, developmental and epileptic encephalopathy, 8, developmental and epileptic encephalopathy, 2, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, developmental and epileptic encephalopathy, 1, developmental and epileptic encephalopathy, 3, developmental and epileptic encephalopathy, 4, microcephaly, seizures, and developmental delay, developmental and epileptic encephalopathy, 5, developmental and epileptic encephalopathy, 7, developmental and epileptic encephalopathy, 11, neonatal-onset encephalopathy with rigidity and seizures, developmental and epileptic encephalopathy, 15, developmental and epileptic encephalopathy, 17, developmental and epileptic encephalopathy, 18, developmental and epileptic encephalopathy, 19, developmental and epileptic encephalopathy, 23, developmental and epileptic encephalopathy, 27, developmental and epileptic encephalopathy, 30, developmental and epileptic encephalopathy, 50, developmental and epileptic encephalopathy, 35, developmental and epileptic encephalopathy, 37, developmental and epileptic encephalopathy, 38, developmental and epileptic encephalopathy, 40, developmental and epileptic encephalopathy, 48, developmental and epileptic encephalopathy, 49, developmental and epileptic encephalopathy, 51, Lennox-Gastaut syndrome, developmental and epileptic encephalopathy 91, developmental and epileptic encephalopathy 92, developmental and epileptic encephalopathy 93, developmental and epileptic encephalopathy 96, developmental and epileptic encephalopathy, 90, developmental and epileptic encephalopathy, 85, with or without midline brain defects, developmental and epileptic encephalopathy, 67, developmental and epileptic encephalopathy, 86, developmental and epileptic encephalopathy, 87, developmental and epileptic encephalopathy, 88, developmental and epileptic encephalopathy 6B, developmental and epileptic encephalopathy 97, developmental and epileptic encephalopathy 98, developmental and epileptic encephalopathy 99, developmental and epileptic encephalopathy 100, developmental and epileptic encephalopathy 101, developmental and epileptic encephalopathy 89, developmental and epileptic encephalopathy 102, developmental and epileptic encephalopathy 103, developmental and epileptic encephalopathy 104, developmental and epileptic encephalopathy 105 with hypopituitarism, developmental and epileptic encephalopathy 106, developmental and epileptic encephalopathy 107, developmental and epileptic encephalopathy, 68, developmental and epileptic encephalopathy, 69, developmental and epileptic encephalopathy, 70, developmental and epileptic encephalopathy, 71, developmental and epileptic encephalopathy, 72, developmental and epileptic encephalopathy, 74, developmental and epileptic encephalopathy, 75, developmental and epileptic encephalopathy, 76, developmental and epileptic encephalopathy, 77, developmental and epileptic encephalopathy, 78, developmental and epileptic encephalopathy, 79, developmental and epileptic encephalopathy, 80, developmental and epileptic encephalopathy, 81, developmental and epileptic encephalopathy, 82, developmental and epileptic encephalopathy, 83, developmental and epileptic encephalopathy, 84, developmental and epileptic encephalopathy, 52, developmental and epileptic encephalopathy, 53, developmental and epileptic encephalopathy, 54, developmental and epileptic encephalopathy, 55, developmental and epileptic encephalopathy, 56, developmental and epileptic encephalopathy, 57, developmental and epileptic encephalopathy, 58, developmental and epileptic encephalopathy, 59, developmental and epileptic encephalopathy, 60, developmental and epileptic encephalopathy, 61, developmental and epileptic encephalopathy, 62, developmental and epileptic encephalopathy, 63, developmental and epileptic encephalopathy, 64, developmental and epileptic encephalopathy, 65, developmental and epileptic encephalopathy, 73, developmental and epileptic encephalopathy, 66, developmental and epileptic encephalopathy, 6A, non-neonatal early infantile epileptic encephalopathy, Dravet syndrome, neonatal-onset developmental and epileptic encephalopathy, hemiplegic migraine-developmental and epileptic encephalopathy spectrum, DNM1-encephalopathy and neurodevelopmental disorder, TMEM63B-related developmental and epileptic encephalopathy with anemia, developmental and epileptic encephalopathy 108, developmental and epileptic encephalopathy 109, developmental and epileptic encephalopathy 110, developmental and epileptic encephalopathy 111, developmental and epileptic encephalopathy 112, developmental and epileptic encephalopathy 113, developmental and epileptic encephalopathy 114, developmental and epileptic encephalopathy 115, developmental and epileptic encephalopathy 116, developmental and epileptic encephalopathy 118, developmental and epileptic encephalopathy 120, developmental and epileptic encephalopathy 121, developmental and epileptic encephalopathy 119

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

316 likely benign, 221 uncertain significance, 31 conflicting classifications of pathogenicity, 12 benign/likely benign, 10 benign, 4 pathogenic, 4 likely pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
126421	NM_020822.3(KCNT1):c.862G>A (p.Gly288Ser)	KCNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1338769	NM_020822.3(KCNT1):c.1424_1485dup (p.Asn496delinsProGlyProTer)	KCNT1	Pathogenic/Likely pathogenic	criteria provided, single submitter
1401332	NM_020822.3(KCNT1):c.2012C>T (p.Thr671Ile)	KCNT1	Pathogenic	criteria provided, single submitter
1457517	NM_020822.3(KCNT1):c.2687T>A (p.Met896Lys)	KCNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1457519	NM_020822.3(KCNT1):c.2797C>G (p.Arg933Gly)	KCNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1525584	NM_020822.3(KCNT1):c.2800G>T (p.Ala934Ser)	KCNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1320152	NM_020822.3(KCNT1):c.1406A>C (p.His469Pro)	KCNT1	Likely pathogenic	criteria provided, single submitter
1328519	NM_020822.3(KCNT1):c.3001A>T (p.Thr1001Ser)	KCNT1	Likely pathogenic	criteria provided, single submitter
1486353	NM_020822.3(KCNT1):c.862G>T (p.Gly288Cys)	KCNT1	Likely pathogenic	criteria provided, single submitter
1503439	NM_020822.3(KCNT1):c.1309C>A (p.Leu437Ile)	KCNT1	Likely pathogenic	criteria provided, single submitter
1001305	NM_020822.3(KCNT1):c.1963G>A (p.Glu655Lys)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1014642	NM_020822.3(KCNT1):c.3538G>A (p.Val1180Ile)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1036350	NM_020822.3(KCNT1):c.2195C>T (p.Ser732Leu)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1038198	NM_020822.3(KCNT1):c.3616C>T (p.His1206Tyr)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1040246	NM_020822.3(KCNT1):c.1770G>A (p.Lys590=)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1096238	NM_020822.3(KCNT1):c.2595-8G>A	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1132077	NM_020822.3(KCNT1):c.16G>A (p.Gly6Arg)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
129352	NM_020822.3(KCNT1):c.1257C>G (p.Val419=)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
129354	NM_020822.3(KCNT1):c.1879A>G (p.Ile627Val)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
129355	NM_020822.3(KCNT1):c.2034C>T (p.Gly678=)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
129360	NM_020822.3(KCNT1):c.2882G>A (p.Arg961His)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1305092	NM_020822.3(KCNT1):c.41G>C (p.Cys14Ser)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1310550	NM_020822.3(KCNT1):c.784C>T (p.Arg262Trp)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1353315	NM_020822.3(KCNT1):c.3340C>G (p.Arg1114Gly)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1401119	NM_020822.3(KCNT1):c.1984G>A (p.Val662Met)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1401663	NM_020822.3(KCNT1):c.3409C>T (p.Arg1137Cys)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1408450	NM_020822.3(KCNT1):c.4C>G (p.Pro2Ala)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1418269	NM_020822.3(KCNT1):c.2050A>C (p.Thr684Pro)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1423830	NM_020822.3(KCNT1):c.1328T>C (p.Met443Thr)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1432042	NM_020822.3(KCNT1):c.518A>G (p.Lys173Arg)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
KCNT1	Definitive	Autosomal dominant	developmental and epileptic encephalopathy, 14	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNT1	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
KCNT1	Orphanet:98784	Sleep-related hypermotor epilepsy
CACNA1E	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
CELF2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
ABCA2	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KCNT1	HGNC:18865	ENSG00000107147	Q5JUK3	Potassium channel subfamily T member 1	gencc,clinvar
VAV2	HGNC:12658	ENSG00000160293	P52735	Guanine nucleotide exchange factor VAV2	clinvar
CACNA1E	HGNC:1392	ENSG00000198216	Q15878	Voltage-dependent R-type calcium channel subunit alpha-1E	clinvar
GPSM1	HGNC:17858	ENSG00000160360	Q86YR5	G-protein-signaling modulator 1	clinvar
CELF2	HGNC:2550	ENSG00000048740	O95319	CUGBP Elav-like family member 2	clinvar
TOR4A	HGNC:25981	ENSG00000198113	Q9NXH8	Torsin-4A	clinvar
ABCA2	HGNC:32	ENSG00000107331	Q9BZC7	ATP-binding cassette sub-family A member 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNT1	Potassium channel subfamily T member 1	Sodium-activated K(+) channel.
VAV2	Guanine nucleotide exchange factor VAV2	Guanine nucleotide exchange factor for the Rho family of Ras-related GTPases.
CACNA1E	Voltage-dependent R-type calcium channel subunit alpha-1E	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells.
GPSM1	G-protein-signaling modulator 1	Guanine nucleotide dissociation inhibitor (GDI) which functions as a receptor-independent activator of heterotrimeric G-protein signaling.
CELF2	CUGBP Elav-like family member 2	RNA-binding protein implicated in the regulation of several post-transcriptional events.
ABCA2	ATP-binding cassette sub-family A member 2	Probable lipid transporter that modulates cholesterol sequestration in the late endosome/lysosome by regulating the intracellular sphingolipid metabolism, in turn participates in cholesterol homeostasis.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.43

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	2	31.9×	0.007
Transporter	1	11.1×	0.173
Scaffold/PPI	1	2.5×	0.455
Other/Unknown	3	0.8×	0.858

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNT1	Ion channel	yes		RCK_N, K_chnl_BK_asu, K_chnl_dom
VAV2	Scaffold/PPI	no		DH_dom, SH2, GDS_CDC24_CS
CACNA1E	Ion channel	yes		EF_hand_dom, VDCCAlpha1, VDCC_R_a1su
GPSM1	Other/Unknown	no		GoLoco_motif, TPR-like_helical_dom_sf, TPR_rpt
CELF2	Other/Unknown	no		RRM_dom, Hud_Sxl_RNA, Nucleotide-bd_a/b_plait_sf
TOR4A	Other/Unknown	no		AAA+_ATPase, Torsin, P-loop_NTPase
ABCA2	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM

Expression context

Cohort genes with no expression data: 0.

7 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right hemisphere of cerebellum	3
cerebellar cortex	1
cerebellar hemisphere	1
ganglionic eminence	1
parotid gland	1
ventricular zone	1
Brodmann (1909) area 23	1
cortical plate	1
middle temporal gyrus	1
cardiac muscle of right atrium	1
tibia	1
CA1 field of hippocampus	1
entorhinal cortex	1
orbitofrontal cortex	1
buccal mucosa cell	1
granulocyte	1
mucosa of transverse colon	1
C1 segment of cervical spinal cord	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNT1	153	tissue_specific	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
VAV2	248	ubiquitous	marker	parotid gland, ganglionic eminence, ventricular zone
CACNA1E	144	broad	marker	middle temporal gyrus, cortical plate, Brodmann (1909) area 23
GPSM1	235	ubiquitous	marker	tibia, cardiac muscle of right atrium, right hemisphere of cerebellum
CELF2	289	ubiquitous	marker	CA1 field of hippocampus, orbitofrontal cortex, entorhinal cortex
TOR4A	184	ubiquitous	marker	buccal mucosa cell, mucosa of transverse colon, granulocyte
ABCA2	234	ubiquitous	marker	C1 segment of cervical spinal cord, spinal cord, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CACNA1E	2,008
VAV2	1,746
ABCA2	1,678
KCNT1	1,562
GPSM1	1,472
CELF2	1,428
TOR4A	437

Structural data

PDB: 4 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VAV2	P52735	7
CELF2	O95319	7
KCNT1	Q5JUK3	6
CACNA1E	Q15878	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TOR4A	Q9NXH8	79.35
ABCA2	Q9BZC7	71.46
GPSM1	Q86YR5	68.24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 33. Enrichment computed across 7 evidence-associated genes (5 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Presynaptic depolarization and calcium channel opening	1	190.3×	0.053	CACNA1E
ABC transporters in lipid homeostasis	1	120.2×	0.053	ABCA2
Signal transduction by L1	1	103.8×	0.053	VAV2
Azathioprine ADME	1	99.3×	0.053	VAV2
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	99.3×	0.053	VAV2
VEGFR2 mediated vascular permeability	1	81.6×	0.053	VAV2
DAP12 signaling	1	73.7×	0.053	VAV2
FCERI mediated Ca+2 mobilization	1	71.4×	0.053	VAV2
FCERI mediated MAPK activation	1	69.2×	0.053	VAV2
GPVI-mediated activation cascade	1	61.7×	0.053	VAV2
EPH-ephrin mediated repulsion of cells	1	43.9×	0.056	VAV2
Regulation of insulin secretion	1	43.9×	0.056	CACNA1E
FCGR3A-mediated phagocytosis	1	37.4×	0.056	VAV2
NRAGE signals death through JNK	1	36.8×	0.056	VAV2
Regulation of actin dynamics for phagocytic cup formation	1	36.8×	0.056	VAV2
Integration of energy metabolism	1	35.1×	0.056	CACNA1E
RHOB GTPase cycle	1	30.9×	0.056	VAV2
RHOG GTPase cycle	1	29.7×	0.056	VAV2
RHOC GTPase cycle	1	29.3×	0.056	VAV2
VEGFA-VEGFR2 Pathway	1	27.9×	0.056	VAV2
G alpha (12/13) signalling events	1	27.5×	0.056	VAV2
RAC2 GTPase cycle	1	25.4×	0.057	VAV2
ABC-family protein mediated transport	1	24.3×	0.057	ABCA2
RAC3 GTPase cycle	1	23.8×	0.057	VAV2
Platelet degranulation	1	17.6×	0.073	TOR4A
Transmission across Chemical Synapses	1	15.2×	0.079	CACNA1E
RHOA GTPase cycle	1	14.9×	0.079	VAV2
CDC42 GTPase cycle	1	14.5×	0.079	VAV2
RAC1 GTPase cycle	1	12.2×	0.090	VAV2
Neuronal System	1	8.8×	0.119	CACNA1E

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of intracellular cholesterol transport	1	2808.7×	0.004	ABCA2
negative regulation of phospholipid biosynthetic process	1	2808.7×	0.004	ABCA2
negative regulation of sphingolipid biosynthetic process	1	2808.7×	0.004	ABCA2
regulation of protein localization to cell periphery	1	2808.7×	0.004	ABCA2
negative regulation of guanyl-nucleotide exchange factor activity	1	2808.7×	0.004	GPSM1
negative regulation of steroid metabolic process	1	1404.3×	0.005	ABCA2
ceramide translocation	1	1404.3×	0.005	ABCA2
regulation of post-translational protein modification	1	1404.3×	0.005	ABCA2
negative regulation of receptor-mediated endocytosis involved in cholesterol transport	1	1404.3×	0.005	ABCA2
positive regulation of low-density lipoprotein particle receptor catabolic process	1	936.2×	0.006	ABCA2
ganglioside metabolic process	1	702.2×	0.007	ABCA2
regulation of intracellular cholesterol transport	1	702.2×	0.007	ABCA2
sphingomyelin metabolic process	1	561.7×	0.007	ABCA2
positive regulation of amyloid precursor protein biosynthetic process	1	561.7×	0.007	ABCA2
intracellular sphingolipid homeostasis	1	561.7×	0.007	ABCA2
negative regulation of cholesterol efflux	1	468.1×	0.008	ABCA2
glycosphingolipid metabolic process	1	401.2×	0.008	ABCA2
regulation of steroid metabolic process	1	401.2×	0.008	ABCA2
central nervous system myelin formation	1	401.2×	0.008	ABCA2
immune response-regulating cell surface receptor signaling pathway	1	312.1×	0.009	VAV2
response to cholesterol	1	280.9×	0.009	ABCA2
positive regulation of amyloid precursor protein catabolic process	1	280.9×	0.009	ABCA2
regulation of protein localization to cell surface	1	280.9×	0.009	ABCA2
negative regulation of GTPase activity	1	175.5×	0.013	GPSM1
sphingosine biosynthetic process	1	175.5×	0.013	ABCA2
positive regulation of amyloid-beta formation	1	147.8×	0.015	ABCA2
response to steroid hormone	1	140.4×	0.016	ABCA2
mRNA splice site recognition	1	133.8×	0.016	CELF2
regulation of cell size	1	127.7×	0.016	VAV2
Fc-epsilon receptor signaling pathway	1	122.1×	0.016	VAV2

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 3 of 7 evidence-associated genes (43%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
KCNT1	BEPRIDIL
CACNA1E	NIMODIPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNT1	2	4
CACNA1E	2	4
VAV2	0	0
GPSM1	0	0
CELF2	0	0
TOR4A	0	0
ABCA2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	KCNT1
QUINIDINE	4	KCNT1
NIMODIPINE	4	CACNA1E
TACRINE	4	CACNA1E

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KCNT1	24	Binding:24
CACNA1E	14	Binding:14
CELF2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

4 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
BEPRIDIL	4	KCNT1
QUINIDINE	4	KCNT1
NIMODIPINE	4	CACNA1E
TACRINE	4	CACNA1E

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	KCNT1, CACNA1E
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	ABCA2
E	Difficult family or no structure, no drug	4	VAV2, GPSM1, CELF2, TOR4A

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
VAV2	0	—
GPSM1	0	—
CELF2	1	—
TOR4A	0	—
ABCA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07600736	PHASE2	RECRUITING	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Clinical Activity of ABS-1230 in Pediatric Participants With KCNT1-related Epilepsy
NCT07156201	PHASE1	RECRUITING	A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of ABS-1230 Given Orally Compared With Placebo in Healthy Participants Aged 18 to 55 Years
NCT04924153	Not specified	COMPLETED	A Natural History Study of Participants With Potassium Sodium-Activated Channel Subfamily T Member 1 (KCNT1)-Related Epilepsy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ESOMEPRAZOLE	4	1