Developmental and epileptic encephalopathy, 7

disease

On this page

Also known as DEE7developmental and epileptic encephalopathy 7EIEE7epileptic encephalopathy, early infantile, 7epileptic encephalopathy, early infantile, type 7KCNQ2-NEEKCNQ2-related disorders

Summary

Developmental and epileptic encephalopathy, 7 (MONDO:0013387) is a disease caused by KCNQ2 (GenCC Definitive), with 8 cohort genes.

At a glance

Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
Causal gene: KCNQ2 (GenCC Definitive)
Cohort genes: 8
ClinVar variants: 313
Phenotypes (HPO): 22

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		11	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Obligate (100%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0002500	Abnormal cerebral white matter morphology	Very frequent (80-99%)
HP:0010818	Generalized tonic seizure	Very frequent (80-99%)
HP:0010851	EEG with burst suppression	Very frequent (80-99%)
HP:0200134	Epileptic encephalopathy	Very frequent (80-99%)
HP:0000980	Pallor	Frequent (30-79%)
HP:0001041	Facial erythema	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0002104	Apnea	Frequent (30-79%)
HP:0002181	Cerebral edema	Frequent (30-79%)
HP:0002453	Abnormal globus pallidus morphology	Frequent (30-79%)
HP:0002540	Inability to walk	Frequent (30-79%)
HP:0007015	Poor gross motor coordination	Frequent (30-79%)
HP:0011097	Epileptic spasm	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0012736	Profound global developmental delay	Frequent (30-79%)
HP:0002059	Cerebral atrophy	Occasional (5-29%)
HP:0002079	Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0002521	Hypsarrhythmia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 7
Mondo ID	MONDO:0013387
OMIM	613720
Orphanet	439218
DOID	DOID:0080462
UMLS	C3150986
MedGen	462336
GARD	0013060
Is cancer (heuristic)	no

Also known as: DEE7 · developmental and epileptic encephalopathy 7 · EIEE7 · epileptic encephalopathy, early infantile, 7 · epileptic encephalopathy, early infantile, type 7 · KCNQ2-NEE · KCNQ2-related disorders

Data availability: 313 ClinVar variants · 4 GenCC gene-disease records · 8 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, 7

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

313 retrieved; paginated sample, class counts are floors:

85 pathogenic, 74 likely pathogenic, 51 pathogenic/likely pathogenic, 47 uncertain significance, 31 conflicting classifications of pathogenicity, 12 not provided, 6 likely benign, 4 benign/likely benign, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1022468	NM_172107.4(KCNQ2):c.1720G>A (p.Gly574Ser)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1029260	NM_172107.4(KCNQ2):c.1420G>T (p.Glu474Ter)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
1034352	NM_172107.4(KCNQ2):c.1160dup (p.Leu388fs)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
1068430	NM_172107.4(KCNQ2):c.1749G>C (p.Lys583Asn)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1164059	NM_172107.4(KCNQ2):c.878T>C (p.Leu293Pro)	KCNQ2	Pathogenic	criteria provided, single submitter
120176	NM_172107.4(KCNQ2):c.794C>T (p.Ala265Val)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
129331	NM_172107.4(KCNQ2):c.1197del (p.Ser399fs)	KCNQ2	Pathogenic	criteria provided, single submitter
1326316	NM_172107.4(KCNQ2):c.171_172delinsAA (p.Arg58Ser)	KCNQ2	Pathogenic	criteria provided, single submitter
1326320	NM_172107.4(KCNQ2):c.1123C>T (p.Gln375Ter)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1326322	NM_172107.4(KCNQ2):c.617T>G (p.Leu206Arg)	KCNQ2	Pathogenic	criteria provided, single submitter
1326326	NM_172107.4(KCNQ2):c.668C>T (p.Ser223Phe)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459931	NM_172107.4(KCNQ2):c.1168C>T (p.Gln390Ter)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1522201	NM_172107.4(KCNQ2):c.811G>A (p.Gly271Ser)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526159	NM_172107.4(KCNQ2):c.569A>T (p.Asn190Ile)	KCNQ2	Pathogenic	criteria provided, single submitter
167208	NM_172107.4(KCNQ2):c.821C>T (p.Thr274Met)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1676605	NM_172107.4(KCNQ2):c.49G>T (p.Glu17Ter)	KCNQ2	Pathogenic	criteria provided, single submitter
1691450	NM_172107.4(KCNQ2):c.652T>A (p.Trp218Arg)	KCNQ2	Pathogenic	criteria provided, single submitter
1701799	NM_172107.4(KCNQ2):c.836G>A (p.Gly279Asp)	KCNQ2	Pathogenic/Likely pathogenic	no assertion criteria provided
1709240	NM_172107.4(KCNQ2):c.850T>C (p.Tyr284His)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
1803046	NM_172107.4(KCNQ2):c.2331dup (p.Glu778fs)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1803794	NM_172107.4(KCNQ2):c.868G>T (p.Gly290Cys)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1805714	NM_172107.4(KCNQ2):c.835G>A (p.Gly279Ser)	KCNQ2	Pathogenic	criteria provided, single submitter
197891	NM_172107.4(KCNQ2):c.793G>A (p.Ala265Thr)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1992305	NM_172107.4(KCNQ2):c.601C>G (p.Arg201Gly)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
202170	NM_172107.4(KCNQ2):c.698_699insACC (p.Val233_Thr234insPro)	KCNQ2	Pathogenic	no assertion criteria provided
205863	NM_172107.4(KCNQ2):c.380A>G (p.Tyr127Cys)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
205864	NM_172107.4(KCNQ2):c.431G>A (p.Arg144Gln)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
205866	NM_172107.4(KCNQ2):c.583T>C (p.Ser195Pro)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
205867	NM_172107.4(KCNQ2):c.593G>A (p.Arg198Gln)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
205869	NM_172107.4(KCNQ2):c.601C>T (p.Arg201Cys)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 12 · 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
KCNQ2	Definitive	Autosomal dominant	developmental and epileptic encephalopathy, 7	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNQ2	Orphanet:140927	Self-limited neonatal-infantile epilepsy
KCNQ2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
KCNQ2	Orphanet:1949	Self-limited neonatal epilepsy
KCNQ2	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
KCNQ2	Orphanet:306	Self-limited infantile epilepsy
KCNQ2	Orphanet:439218	KCNQ2-related developmental and epileptic encephalopathy
CHRNA4	Orphanet:98784	Sleep-related hypermotor epilepsy
EEF1A2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
EEF1A2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
IL6ST	Orphanet:656283	Autosomal recessive combined immunodeficiency due to complete IL6ST deficiency
IL6ST	Orphanet:656300	Autosomal recessive combined immunodeficiency due to partial IL6ST deficiency
IL6ST	Orphanet:656313	Autosomal dominant combined immunodeficiency due to partial IL6ST deficiency

Cohort genes → proteins

8 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KCNQ2	HGNC:6296	ENSG00000075043	O43526	Potassium voltage-gated channel subfamily KQT member 2	gencc,clinvar
COL20A1	HGNC:14670	ENSG00000101203	Q9P218	Collagen alpha-1(XX) chain	clinvar
ABHD16B	HGNC:16128	ENSG00000183260	Q9H3Z7	ABHD16B	clinvar
CHRNA4	HGNC:1958	ENSG00000101204	P43681	Neuronal acetylcholine receptor subunit alpha-4	clinvar
EEF1A2	HGNC:3192	ENSG00000101210	Q05639	Elongation factor 1-alpha 2	clinvar
HAR1B	HGNC:33118	ENSG00000231133		highly accelerated region 1B	clinvar
GMEB2	HGNC:4371	ENSG00000101216	Q9UKD1	Glucocorticoid modulatory element-binding protein 2	clinvar
IL6ST	HGNC:6021	ENSG00000134352	P40189	Interleukin-6 receptor subunit beta	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNQ2	Potassium voltage-gated channel subfamily KQT member 2	Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability.
COL20A1	Collagen alpha-1(XX) chain	Probable collagen protein.
ABHD16B	ABHD16B	Hydrolyzes the sn-1 position of glycerophospholipids with high specificity towards phosphatidylserine (PS), PS-PLA1 enzyme.
CHRNA4	Neuronal acetylcholine receptor subunit alpha-4	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…
EEF1A2	Elongation factor 1-alpha 2	Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis.
GMEB2	Glucocorticoid modulatory element-binding protein 2	Trans-acting factor that binds to glucocorticoid modulatory elements (GME) present in the TAT (tyrosine aminotransferase) promoter and increases sensitivity to low concentrations of glucocorticoids.
IL6ST	Interleukin-6 receptor subunit beta	Signal-transducing molecule.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 5 · Druggable fraction: 0.38

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
Antibody/Immunoglobulin	2	7.3×	0.086
Ion channel	1	13.9×	0.104
Other/Unknown	5	1.1×	0.496

Per-gene assignment

Symbol	Family	Druggable?	InterPro (top 3)
KCNQ2	Ion channel	yes	K_chnl_volt-dep_KCNQ, K_chnl_volt-dep_KCNQ2, Ion_trans_dom
COL20A1	Antibody/Immunoglobulin	yes	VWF_A, FN3_dom, Collagen
ABHD16B	Other/Unknown	no	AB_hydrolase_1, AB_hydrolase_fold
CHRNA4	Other/Unknown	no	Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
EEF1A2	Other/Unknown	no	T_Tr_GTP-bd_dom, EFTu-like_2, Transl_elong_EF1A_euk/arc
HAR1B	Other/Unknown	no
GMEB2	Other/Unknown	no	SAND_dom, SAND-like_dom_sf, GMEB1/2/Spe-44_dom
IL6ST	Antibody/Immunoglobulin	yes	Hematopoietin_rcpt_Gp130_CS, FN3_dom, IgC2-like_lig-bd

Expression context

Cohort genes with no expression data: 0.

4 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	2
right testis	2
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
anterior cingulate cortex	1
testis	1
cingulate cortex	1
cortical plate	1
right lobe of liver	1
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	1
nucleus accumbens	1
primordial germ cell in gonad	1
buccal mucosa cell	1
parotid gland	1
thymus	1
germinal epithelium of ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNQ2	183	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
COL20A1	133	tissue_specific	marker	right testis, left testis, anterior cingulate cortex
ABHD16B	106		yes	right testis, left testis, testis
CHRNA4	138	tissue_specific	yes	right lobe of liver, cortical plate, cingulate cortex
EEF1A2	247	ubiquitous	marker	gastrocnemius, apex of heart, hindlimb stylopod muscle
HAR1B	123	broad	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, nucleus accumbens
GMEB2	269	ubiquitous	yes	parotid gland, buccal mucosa cell, thymus
IL6ST	295	ubiquitous	marker	parietal pleura, pleura, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNQ2	3,388
CHRNA4	1,989
IL6ST	1,530
GMEB2	1,200
COL20A1	975
EEF1A2	745
ABHD16B	427
HAR1B	0

Intra-cohort edges

A	B	Sources
CHRNA4	KCNQ2	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNQ2	O43526	39
IL6ST	P40189	20
CHRNA4	P43681	12
COL20A1	Q9P218	4
EEF1A2	Q05639	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABHD16B	Q9H3Z7	86.64
GMEB2	Q9UKD1	61.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 8 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
Highly sodium permeable postsynaptic acetylcholine nicotinic receptors	1	326.3×	0.013	CHRNA4
Highly calcium permeable nicotinic acetylcholine receptors	1	253.8×	0.013	CHRNA4
MAPK1 (ERK2) activation	1	228.4×	0.013	IL6ST
MAPK3 (ERK1) activation	1	207.6×	0.013	IL6ST
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	1	207.6×	0.013	CHRNA4
Interleukin-27 signaling	1	207.6×	0.013	IL6ST
Interleukin-6 signaling	1	190.3×	0.013	IL6ST
Presynaptic nicotinic acetylcholine receptors	1	190.3×	0.013	CHRNA4
Interleukin-35 Signalling	1	190.3×	0.013	IL6ST
Acetylcholine binding and downstream events	1	163.1×	0.013	CHRNA4
Postsynaptic nicotinic acetylcholine receptors	1	163.1×	0.013	CHRNA4
Neuronal System	2	17.7×	0.013	KCNQ2, CHRNA4
IL-6-type cytokine receptor ligand interactions	1	126.9×	0.016	IL6ST
Interaction between L1 and Ankyrins	1	73.7×	0.025	KCNQ2
Eukaryotic Translation Elongation	1	55.7×	0.031	EEF1A2
Collagen chain trimerization	1	51.9×	0.031	COL20A1
Voltage gated Potassium channels	1	48.6×	0.031	KCNQ2
Collagen biosynthesis and modifying enzymes	1	34.1×	0.041	COL20A1
Activation of STAT3 by cadherin engagement	1	32.6×	0.041	IL6ST
Potassium Channels	1	26.9×	0.048	KCNQ2
L1CAM interactions	1	24.0×	0.051	KCNQ2
Neurotransmitter receptors and postsynaptic signal transmission	1	20.0×	0.058	CHRNA4
Transmission across Chemical Synapses	1	15.2×	0.072	CHRNA4
Axon guidance	1	9.0×	0.115	KCNQ2
Nervous system development	1	8.6×	0.116	KCNQ2
Developmental Biology	1	2.9×	0.301	KCNQ2

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
action potential	2	119.5×	0.007	KCNQ2, CHRNA4
positive regulation of lipid kinase activity	1	2808.7×	0.011	EEF1A2
negative regulation of interleukin-6-mediated signaling pathway	1	1404.3×	0.012	IL6ST
phosphatidylserine catabolic process	1	702.2×	0.012	ABHD16B
oncostatin-M-mediated signaling pathway	1	702.2×	0.012	IL6ST
leukemia inhibitory factor signaling pathway	1	702.2×	0.012	IL6ST
interleukin-11-mediated signaling pathway	1	561.7×	0.012	IL6ST
ciliary neurotrophic factor-mediated signaling pathway	1	561.7×	0.012	IL6ST
regulation of chaperone-mediated autophagy	1	561.7×	0.012	EEF1A2
monoacylglycerol catabolic process	1	401.2×	0.012	ABHD16B
interleukin-27-mediated signaling pathway	1	401.2×	0.012	IL6ST
chemical synaptic transmission	2	25.8×	0.012	KCNQ2, CHRNA4
positive regulation of adaptive immune response	1	351.1×	0.013	IL6ST
behavioral response to nicotine	1	312.1×	0.013	CHRNA4
inhibitory postsynaptic potential	1	280.9×	0.013	CHRNA4
intestinal epithelial cell development	1	255.3×	0.013	IL6ST
T-helper 17 cell lineage commitment	1	255.3×	0.013	IL6ST
positive regulation of acute inflammatory response	1	234.1×	0.013	IL6ST
positive regulation of astrocyte differentiation	1	234.1×	0.013	IL6ST
positive regulation of platelet aggregation	1	216.1×	0.013	IL6ST
translational elongation	1	200.6×	0.013	EEF1A2
regulation of dopamine secretion	1	200.6×	0.013	CHRNA4
nervous system process	1	200.6×	0.013	CHRNA4
interleukin-6-mediated signaling pathway	1	187.2×	0.013	IL6ST
synaptic transmission, cholinergic	1	133.8×	0.018	CHRNA4
positive regulation of cardiac muscle hypertrophy	1	122.1×	0.019	IL6ST
acetylcholine receptor signaling pathway	1	104.0×	0.021	CHRNA4
neuromuscular synaptic transmission	1	100.3×	0.021	CHRNA4
cell surface receptor signaling pathway via STAT	1	93.6×	0.022	IL6ST
glycogen metabolic process	1	87.8×	0.022	IL6ST

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 6

Druggability breadth: 4 of 8 evidence-associated genes (50%) 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
KCNQ2	FLUPIRTINE
CHRNA4	VARENICLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHRNA4	64	4
KCNQ2	4	4
COL20A1	0	0
ABHD16B	0	0
EEF1A2	0	0
HAR1B	0	0
GMEB2	0	0
IL6ST	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FLUPIRTINE	4	KCNQ2
EZOGABINE	4	KCNQ2
VARENICLINE	4	CHRNA4
PONATINIB	4	CHRNA4
CHLOROPROCAINE	4	CHRNA4
ANISOTROPINE	4	CHRNA4
PALONOSETRON	4	CHRNA4
CHLORPHENTERMINE	4	CHRNA4
PYRVINIUM	4	CHRNA4
DIPHEMANIL	4	CHRNA4
SERTINDOLE	4	CHRNA4
ATRACURIUM	4	CHRNA4
NITAZOXANIDE	4	CHRNA4
ILOPERIDONE	4	CHRNA4
MOXISYLYTE	4	CHRNA4
RIFAXIMIN	4	CHRNA4
DAUNORUBICIN	4	CHRNA4
PALBOCICLIB	4	CHRNA4
OXYPERTINE	4	CHRNA4
VANDETANIB	4	CHRNA4
MEDAZEPAM	4	CHRNA4
RIFAMPIN	4	CHRNA4
ZIMELDINE	4	CHRNA4
THIORIDAZINE	4	CHRNA4
SUNITINIB	4	CHRNA4
EPALRESTAT	4	CHRNA4
NIMESULIDE	4	CHRNA4
TROPISETRON	4	CHRNA4
FENTANYL	4	CHRNA4
CRIZOTINIB	4	CHRNA4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CHRNA4	624	Binding:497, Functional:125, Toxicity:1, ADMET:1
KCNQ2	145	Binding:136, Functional:7, ADMET:1, Toxicity:1
IL6ST	21	Binding:21
EEF1A2	8	Binding:8

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
KCNQ2	145
CHRNA4	624

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
FLUPIRTINE	4	KCNQ2
EZOGABINE	4	KCNQ2
VARENICLINE	4	CHRNA4
PONATINIB	4	CHRNA4
CHLOROPROCAINE	4	CHRNA4
ANISOTROPINE	4	CHRNA4
PALONOSETRON	4	CHRNA4
CHLORPHENTERMINE	4	CHRNA4
PYRVINIUM	4	CHRNA4
DIPHEMANIL	4	CHRNA4
SERTINDOLE	4	CHRNA4
ATRACURIUM	4	CHRNA4
NITAZOXANIDE	4	CHRNA4
ILOPERIDONE	4	CHRNA4
MOXISYLYTE	4	CHRNA4
RIFAXIMIN	4	CHRNA4
DAUNORUBICIN	4	CHRNA4
PALBOCICLIB	4	CHRNA4
OXYPERTINE	4	CHRNA4
VANDETANIB	4	CHRNA4
MEDAZEPAM	4	CHRNA4
RIFAMPIN	4	CHRNA4
ZIMELDINE	4	CHRNA4
THIORIDAZINE	4	CHRNA4
SUNITINIB	4	CHRNA4
EPALRESTAT	4	CHRNA4
NIMESULIDE	4	CHRNA4
TROPISETRON	4	CHRNA4
FENTANYL	4	CHRNA4
CRIZOTINIB	4	CHRNA4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	KCNQ2, CHRNA4
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	COL20A1, IL6ST
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	ABHD16B, EEF1A2, HAR1B, GMEB2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL20A1	0	—
ABHD16B	0	—
EEF1A2	8	—
HAR1B	0	—
GMEB2	0	—
IL6ST	21	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: KCNQ2, COL20A1, ABHD16B, CHRNA4, EEF1A2, HAR1B, GMEB2, IL6ST