Seizures, benign familial neonatal, 1

Summary

Seizures, benign familial neonatal, 1 (MONDO:0007365) is a disease caused by KCNQ2 (GenCC Definitive), with 9 cohort genes.

At a glance

• Causal gene: KCNQ2 (GenCC Definitive)
• Cohort genes: 9
• ClinVar variants: 265

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	seizures, benign familial neonatal, 1
Mondo ID	MONDO:0007365
MeSH	C567743
OMIM	121200
UMLS	C3149074
MedGen	460425
GARD	0009765
Is cancer (heuristic)	no

Also known as: benign neonatal seizures caused by mutation in KCNQ2 · BFNS1 · KCNQ2 benign neonatal seizures · myokymia · seizures, benign familial neonatal, 1 · seizures, benign familial neonatal, type 1 · seizures, benign neonatal, 1

Data availability: 265 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › epilepsy syndrome › neonatal epilepsy syndrome › benign neonatal seizures › seizures, benign familial neonatal, 1

Related subtypes (3): seizures, benign familial neonatal, 2, seizures, benign familial neonatal, autosomal recessive, seizures, benign familial neonatal, 3

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

265 retrieved; paginated sample, class counts are floors:

93 pathogenic, 43 likely pathogenic, 37 pathogenic/likely pathogenic, 35 not provided, 27 conflicting classifications of pathogenicity, 21 uncertain significance, 5 benign, 2 benign/likely benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1264345	NM_152296.5(ATP1A3):c.1115del (p.Thr372fs)	ATP1A3	Pathogenic	no assertion criteria provided
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
120176	NM_172107.4(KCNQ2):c.794C>T (p.Ala265Val)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
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
167208	NM_172107.4(KCNQ2):c.821C>T (p.Thr274Met)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685897	NM_172107.4(KCNQ2):c.761A>C (p.Glu254Ala)	KCNQ2	Pathogenic	criteria provided, single submitter
1685898	NM_172107.4(KCNQ2):c.700A>G (p.Thr234Ala)	KCNQ2	Pathogenic	criteria provided, single submitter
1685899	NM_172107.4(KCNQ2):c.638G>T (p.Arg213Leu)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685900	NM_172107.4(KCNQ2):c.3G>A (p.Met1Ile)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
1700189	NM_172107.4(KCNQ2):c.807G>T (p.Trp269Cys)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
1701799	NM_172107.4(KCNQ2):c.836G>A (p.Gly279Asp)	KCNQ2	Pathogenic/Likely pathogenic	no assertion criteria provided
1805909	NM_172107.4(KCNQ2):c.195_198del (p.Lys66fs)	KCNQ2	Pathogenic	criteria provided, single submitter
2034758	NM_172107.4(KCNQ2):c.387+1G>A	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
205861	NM_172107.4(KCNQ2):c.297-2A>G	KCNQ2	Pathogenic	criteria provided, single submitter
205863	NM_172107.4(KCNQ2):c.380A>G (p.Tyr127Cys)	KCNQ2	Pathogenic/Likely 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
205873	NM_172107.4(KCNQ2):c.628C>T (p.Arg210Cys)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
205878	NM_172107.4(KCNQ2):c.740C>T (p.Ser247Leu)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
205886	NM_172107.4(KCNQ2):c.881C>T (p.Ala294Val)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
205888	NM_172107.4(KCNQ2):c.916G>C (p.Ala306Pro)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
205892	NM_172107.4(KCNQ2):c.1004C>T (p.Pro335Leu)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
205898	NM_172107.4(KCNQ2):c.1057C>T (p.Arg353Cys)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
205912	NM_172107.4(KCNQ2):c.1639C>T (p.Arg547Trp)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
205913	NM_172107.4(KCNQ2):c.1657C>T (p.Arg553Trp)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
205917	NM_172107.4(KCNQ2):c.1687G>A (p.Asp563Asn)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
205940	NM_172107.4(KCNQ2):c.333_334del (p.Ser113fs)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 13 · 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	seizures, benign familial neonatal, 1	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
ATP1A3	Orphanet:1171	Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome
ATP1A3	Orphanet:2131	Alternating hemiplegia of childhood
ATP1A3	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
ATP1A3	Orphanet:71517	Rapid-onset dystonia-parkinsonism

Cohort genes → proteins

9 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

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
PPDPF	HGNC:16142	ENSG00000125534	Q9H3Y8	Pancreatic progenitor cell differentiation and proliferation factor	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
ATP1A3	HGNC:801	ENSG00000105409	P13637	Sodium/potassium-transporting ATPase subunit alpha-3	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.
PPDPF	Pancreatic progenitor cell differentiation and proliferation factor	Probable regulator of exocrine pancreas development.
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.
ATP1A3	Sodium/potassium-transporting ATPase subunit alpha-3	This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 6 · Druggable fraction: 0.22

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	1	12.4×	0.312
Antibody/Immunoglobulin	1	3.2×	0.507
Other/Unknown	6	1.2×	0.507
Transcription factor	1	0.9×	0.687

Per-gene assignment

Symbol	Family	Druggable?	EC	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
PPDPF	Other/Unknown	no		PPDPF
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
ATP1A3	Transcription factor	no		P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC

Expression context

Cohort genes with no expression data: 0.

5 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	2
right testis	2
cortical plate	2
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
anterior cingulate cortex	1
testis	1
lower esophagus mucosa	1
mucosa of transverse colon	1
right coronary artery	1
cingulate cortex	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

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
PPDPF	262	ubiquitous	marker	lower esophagus mucosa, right coronary artery, mucosa of transverse colon
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
ATP1A3	129	broad	marker	superior frontal gyrus, primary visual cortex, cortical plate

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP1A3	3,876
KCNQ2	3,388
CHRNA4	1,989
GMEB2	1,200
COL20A1	975
EEF1A2	745
PPDPF	439
ABHD16B	427
HAR1B	0

Intra-cohort edges

A	B	Sources
CHRNA4	KCNQ2	string_interaction
GMEB2	PPDPF	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 3 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNQ2	O43526	39
CHRNA4	P43681	12
ATP1A3	P13637	5
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
PPDPF	Q9H3Y8	60.64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 30. Enrichment computed across 9 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×	0.026	CHRNA4
Highly calcium permeable nicotinic acetylcholine receptors	1	253.8×	0.026	CHRNA4
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	1	207.6×	0.026	CHRNA4
Presynaptic nicotinic acetylcholine receptors	1	190.3×	0.026	CHRNA4
Acetylcholine binding and downstream events	1	163.1×	0.026	CHRNA4
Postsynaptic nicotinic acetylcholine receptors	1	163.1×	0.026	CHRNA4
Neuronal System	2	17.7×	0.026	KCNQ2, CHRNA4
Interaction between L1 and Ankyrins	1	73.7×	0.051	KCNQ2
Eukaryotic Translation Elongation	1	55.7×	0.056	EEF1A2
Collagen chain trimerization	1	51.9×	0.056	COL20A1
Voltage gated Potassium channels	1	48.6×	0.056	KCNQ2
Ion transport by P-type ATPases	1	41.5×	0.056	ATP1A3
Ion homeostasis	1	40.8×	0.056	ATP1A3
Collagen biosynthesis and modifying enzymes	1	34.1×	0.062	COL20A1
Potassium Channels	1	26.9×	0.073	KCNQ2
L1CAM interactions	1	24.0×	0.075	KCNQ2
Potential therapeutics for SARS	1	22.8×	0.075	ATP1A3
Cardiac conduction	1	21.8×	0.075	ATP1A3
Neurotransmitter receptors and postsynaptic signal transmission	1	20.0×	0.077	CHRNA4
Ion channel transport	1	19.2×	0.077	ATP1A3
Muscle contraction	1	15.4×	0.087	ATP1A3
Transmission across Chemical Synapses	1	15.2×	0.087	CHRNA4
SARS-CoV Infections	1	11.1×	0.113	ATP1A3
Axon guidance	1	9.0×	0.132	KCNQ2
Nervous system development	1	8.6×	0.133	KCNQ2
Viral Infection Pathways	1	6.2×	0.176	ATP1A3
Transport of small molecules	1	5.0×	0.199	ATP1A3
Infectious disease	1	5.0×	0.199	ATP1A3
Developmental Biology	1	2.9×	0.312	KCNQ2
Disease	1	2.6×	0.328	ATP1A3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 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	102.4×	0.008	KCNQ2, CHRNA4
positive regulation of lipid kinase activity	1	2407.4×	0.010	EEF1A2
phosphatidylserine catabolic process	1	601.9×	0.019	ABHD16B
regulation of chaperone-mediated autophagy	1	481.5×	0.019	EEF1A2
monoacylglycerol catabolic process	1	343.9×	0.019	ABHD16B
response to glycoside	1	343.9×	0.019	ATP1A3
behavioral response to nicotine	1	267.5×	0.019	CHRNA4
inhibitory postsynaptic potential	1	240.7×	0.019	CHRNA4
cell communication by electrical coupling involved in cardiac conduction	1	200.6×	0.019	ATP1A3
regulation of resting membrane potential	1	185.2×	0.019	ATP1A3
translational elongation	1	172.0×	0.019	EEF1A2
regulation of dopamine secretion	1	172.0×	0.019	CHRNA4
nervous system process	1	172.0×	0.019	CHRNA4
neuron projection maintenance	1	160.5×	0.019	ATP1A3
sodium ion export across plasma membrane	1	150.5×	0.019	ATP1A3
cellular response to steroid hormone stimulus	1	150.5×	0.019	ATP1A3
chemical synaptic transmission	2	22.1×	0.019	KCNQ2, CHRNA4
intracellular potassium ion homeostasis	1	141.6×	0.019	ATP1A3
synaptic transmission, cholinergic	1	114.6×	0.021	CHRNA4
TORC1 signaling	1	114.6×	0.021	PPDPF
intracellular sodium ion homeostasis	1	109.4×	0.021	ATP1A3
acetylcholine receptor signaling pathway	1	89.2×	0.024	CHRNA4
neuromuscular synaptic transmission	1	86.0×	0.024	CHRNA4
membrane depolarization	1	73.0×	0.027	CHRNA4
B cell activation	1	65.1×	0.028	CHRNA4
presynaptic modulation of chemical synaptic transmission	1	65.1×	0.028	CHRNA4
response to nicotine	1	60.2×	0.029	CHRNA4
cellular response to amyloid-beta	1	56.0×	0.030	ATP1A3
sensory perception of pain	1	53.5×	0.030	CHRNA4
potassium ion import across plasma membrane	1	52.3×	0.030	ATP1A3

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 9 evidence-associated genes (44%) 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
ATP1A3	OMEPRAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHRNA4	64	4
ATP1A3	5	4
KCNQ2	4	4
COL20A1	0	0
ABHD16B	0	0
PPDPF	0	0
EEF1A2	0	0
HAR1B	0	0
GMEB2	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
ATP1A3	45	Binding:45
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: 9; 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)	3	KCNQ2, CHRNA4, ATP1A3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	COL20A1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	ABHD16B, PPDPF, 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	—
PPDPF	0	—
EEF1A2	8	—
HAR1B	0	—
GMEB2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.