Developmental and epileptic encephalopathy, 76
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Also known as DEE76developmental and epileptic encephalopathy 76EIEE76EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 76
Summary
Developmental and epileptic encephalopathy, 76 (MONDO:0032768) is a disease caused by ACTL6B (GenCC Definitive), with 3 cohort genes.
At a glance
- Causal gene: ACTL6B (GenCC Definitive)
- Cohort genes: 3
- ClinVar variants: 49
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | developmental and epileptic encephalopathy, 76 |
| Mondo ID | MONDO:0032768 |
| OMIM | 618468 |
| DOID | DOID:0112212 |
| UMLS | C5193113 |
| MedGen | 1673011 |
| GARD | 0016355 |
| Is cancer (heuristic) | no |
Also known as: DEE76 · developmental and epileptic encephalopathy 76 · EIEE76 · EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 76 · epileptic encephalopathy, early infantile, 76
Data availability: 49 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.
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, 76
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, 14, 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, 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
49 retrieved; paginated sample, class counts are floors:
18 likely pathogenic, 15 uncertain significance, 9 pathogenic, 3 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 1 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2500134 | NM_016188.5(ACTL6B):c.1114-1G>A | ACTL6B | Pathogenic | no assertion criteria provided |
| 2500135 | NM_016188.5(ACTL6B):c.1120C>T (p.Arg374Ter) | ACTL6B | Pathogenic | criteria provided, single submitter |
| 2500136 | NM_016188.5(ACTL6B):c.1267C>T (p.Arg423Ter) | ACTL6B | Pathogenic | no assertion criteria provided |
| 2500138 | NM_016188.5(ACTL6B):c.279G>A (p.Trp93Ter) | ACTL6B | Pathogenic | no assertion criteria provided |
| 2500141 | NM_016188.5(ACTL6B):c.628del (p.Met210fs) | ACTL6B | Pathogenic | no assertion criteria provided |
| 3376821 | NM_016188.5(ACTL6B):c.604C>T (p.Gln202Ter) | ACTL6B | Pathogenic | criteria provided, single submitter |
| 4293542 | NM_016188.5(ACTL6B):c.149del (p.Gly50fs) | ACTL6B | Pathogenic | criteria provided, single submitter |
| 635099 | NM_016188.5(ACTL6B):c.999T>A (p.Cys333Ter) | ACTL6B | Pathogenic | criteria provided, single submitter |
| 635102 | NM_016188.5(ACTL6B):c.1279del (p.Ter427AspextTer?) | ACTL6B | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 692138 | NM_016188.5(ACTL6B):c.556C>T (p.Gln186Ter) | ACTL6B | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 828105 | NM_016188.5(ACTL6B):c.1087C>T (p.Arg363Ter) | ACTL6B | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 197187 | NM_001165963.4(SCN1A):c.602+1G>A | SCN1A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1679718 | NM_016188.5(ACTL6B):c.1225del (p.Ser409fs) | ACTL6B | Likely pathogenic | criteria provided, single submitter |
| 2431410 | NM_016188.5(ACTL6B):c.369+1G>C | ACTL6B | Likely pathogenic | criteria provided, single submitter |
| 2500130 | NM_016188.5(ACTL6B):c.70C>T (p.Arg24Cys) | ACTL6B | Likely pathogenic | no assertion criteria provided |
| 2500131 | NM_016188.5(ACTL6B):c.832C>T (p.Gln278Ter) | ACTL6B | Likely pathogenic | criteria provided, single submitter |
| 2500132 | NM_016188.5(ACTL6B):c.880T>G (p.Tyr294Asp) | ACTL6B | Likely pathogenic | no assertion criteria provided |
| 2500133 | NM_016188.5(ACTL6B):c.884G>A (p.Gly295Asp) | ACTL6B | Likely pathogenic | no assertion criteria provided |
| 2500137 | NM_016188.5(ACTL6B):c.85G>A (p.Gly29Arg) | ACTL6B | Likely pathogenic | no assertion criteria provided |
| 2500140 | NM_016188.5(ACTL6B):c.497T>C (p.Val166Ala) | ACTL6B | Likely pathogenic | no assertion criteria provided |
| 2500142 | NM_016188.5(ACTL6B):c.695dup (p.Asn233fs) | ACTL6B | Likely pathogenic | criteria provided, single submitter |
| 3767125 | NM_016188.5(ACTL6B):c.11dup (p.Val5fs) | ACTL6B | Likely pathogenic | criteria provided, single submitter |
| 402140 | NM_016188.5(ACTL6B):c.893G>A (p.Arg298Gln) | ACTL6B | Likely pathogenic | criteria provided, single submitter |
| 635100 | NM_016188.5(ACTL6B):c.820C>T (p.Gln274Ter) | ACTL6B | Likely pathogenic | criteria provided, single submitter |
| 635101 | NM_016188.5(ACTL6B):c.1045G>A (p.Gly349Ser) | ACTL6B | Likely pathogenic | criteria provided, single submitter |
| 635104 | NM_016188.5(ACTL6B):c.724C>T (p.Gln242Ter) | ACTL6B | Likely pathogenic | criteria provided, single submitter |
| 635105 | NM_016188.5(ACTL6B):c.617T>C (p.Leu206Pro) | ACTL6B | Likely pathogenic | criteria provided, single submitter |
| 692137 | NM_016188.5(ACTL6B):c.289C>T (p.Arg97Ter) | ACTL6B | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 692141 | NM_016188.5(ACTL6B):c.852C>G (p.Tyr284Ter) | ACTL6B | Likely pathogenic | criteria provided, single submitter |
| 692142 | NM_016188.5(ACTL6B):c.740G>A (p.Trp247Ter) | ACTL6B | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 10 · Orphanet: 17 · 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 |
|---|---|---|---|---|
| ACTL6B | Definitive | Autosomal recessive | developmental and epileptic encephalopathy, 76 | 10 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| ACTL6B | Orphanet:442835 | Non-specific early-onset epileptic encephalopathy |
| ACTL6B | Orphanet:528084 | Non-specific syndromic intellectual disability |
| SCN1A | Orphanet:1942 | Epilepsy with myoclonic-atonic seizures |
| SCN1A | Orphanet:2382 | Lennox-Gastaut syndrome |
| SCN1A | Orphanet:293181 | Epilepsy of infancy with migrating focal seizures |
| SCN1A | Orphanet:33069 | Dravet syndrome |
| SCN1A | Orphanet:36387 | Genetic epilepsy with febrile seizure plus |
| SCN1A | Orphanet:442835 | Non-specific early-onset epileptic encephalopathy |
| SCN1A | Orphanet:569 | Familial or sporadic hemiplegic migraine |
| SCN2A | Orphanet:140927 | Self-limited neonatal-infantile epilepsy |
| SCN2A | Orphanet:1934 | Early infantile developmental and epileptic encephalopathy |
| SCN2A | Orphanet:2131 | Alternating hemiplegia of childhood |
| SCN2A | Orphanet:293181 | Epilepsy of infancy with migrating focal seizures |
| SCN2A | Orphanet:306 | Self-limited infantile epilepsy |
| SCN2A | Orphanet:33069 | Dravet syndrome |
| SCN2A | Orphanet:36387 | Genetic epilepsy with febrile seizure plus |
| SCN2A | Orphanet:697160 | Infantile epileptic spasms syndrome |
Cohort genes → proteins
3 cohort genes, 3 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 3 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| ACTL6B | HGNC:160 | ENSG00000077080 | O94805 | Actin-like protein 6B | gencc,clinvar |
| SCN1A | HGNC:10585 | ENSG00000144285 | P35498 | Sodium channel protein type 1 subunit alpha | clinvar |
| SCN2A | HGNC:10588 | ENSG00000136531 | Q99250 | Sodium channel protein type 2 subunit alpha | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| ACTL6B | Actin-like protein 6B | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). |
| SCN1A | Sodium channel protein type 1 subunit alpha | Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. |
| SCN2A | Sodium channel protein type 2 subunit alpha | Mediates the voltage-dependent sodium ion permeability of excitable membranes. |
Protein-family classification
Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67
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 | 74.3× | 5e-04 |
| Other/Unknown | 1 | 0.6× | 0.914 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| ACTL6B | Other/Unknown | no | Actin, Actin_CS, ATPase_NBD | |
| SCN1A | Ion channel | yes | Na_channel_asu, Ion_trans_dom, Na_channel_a1su | |
| SCN2A | Ion channel | yes | IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom |
Expression context
Cohort genes with no expression data: 0.
3 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) | 3 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| Brodmann (1909) area 23 | 2 |
| cerebellar hemisphere | 1 |
| cortical plate | 1 |
| right hemisphere of cerebellum | 1 |
| lateral nuclear group of thalamus | 1 |
| primary visual cortex | 1 |
| cerebellar vermis | 1 |
| middle temporal gyrus | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| ACTL6B | 164 | broad | marker | cortical plate, right hemisphere of cerebellum, cerebellar hemisphere |
| SCN1A | 154 | tissue_specific | marker | Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex |
| SCN2A | 187 | broad | marker | middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ACTL6B | 4,543 |
| SCN2A | 2,810 |
| SCN1A | 2,287 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| SCN1A | SCN2A | biogrid_interaction, string_interaction |
Structural data
PDB: 2 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SCN2A | Q99250 | 5 |
| SCN1A | P35498 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ACTL6B | O94805 | 91.52 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Interaction between L1 and Ankyrins | 2 | 245.6× | 2e-04 | SCN1A, SCN2A |
| Phase 0 - rapid depolarisation | 2 | 230.7× | 2e-04 | SCN1A, SCN2A |
| L1CAM interactions | 2 | 80.1× | 0.001 | SCN1A, SCN2A |
| Cardiac conduction | 2 | 72.5× | 0.001 | SCN1A, SCN2A |
| Muscle contraction | 2 | 51.4× | 0.002 | SCN1A, SCN2A |
| Axon guidance | 2 | 30.1× | 0.005 | SCN1A, SCN2A |
| Nervous system development | 2 | 28.6× | 0.005 | SCN1A, SCN2A |
| Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 1 | 152.3× | 0.016 | ACTL6B |
| Sensory perception of taste | 1 | 112.0× | 0.020 | SCN2A |
| RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known | 1 | 100.2× | 0.020 | ACTL6B |
| Sensory perception of sweet, bitter, and umami (glutamate) taste | 1 | 92.8× | 0.020 | SCN2A |
| Developmental Biology | 2 | 9.6× | 0.023 | SCN1A, SCN2A |
| RMTs methylate histone arginines | 1 | 48.8× | 0.029 | ACTL6B |
| Transcriptional regulation by RUNX1 | 1 | 48.8× | 0.029 | ACTL6B |
| Sensory Perception | 1 | 31.7× | 0.042 | SCN2A |
| Chromatin organization | 1 | 27.2× | 0.045 | ACTL6B |
| Chromatin modifying enzymes | 1 | 24.1× | 0.048 | ACTL6B |
| RNA Polymerase II Transcription | 1 | 7.5× | 0.142 | ACTL6B |
| Gene expression (Transcription) | 1 | 6.0× | 0.167 | ACTL6B |
| Generic Transcription Pathway | 1 | 5.0× | 0.186 | ACTL6B |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| cardiac muscle cell action potential involved in contraction | 2 | 468.1× | 2e-04 | SCN1A, SCN2A |
| neuronal action potential | 2 | 321.0× | 2e-04 | SCN1A, SCN2A |
| sodium ion transport | 2 | 181.2× | 5e-04 | SCN1A, SCN2A |
| sodium ion transmembrane transport | 2 | 135.4× | 6e-04 | SCN1A, SCN2A |
| intrinsic apoptotic signaling pathway in response to osmotic stress | 1 | 2808.7× | 0.002 | SCN2A |
| nervous system development | 2 | 30.6× | 0.008 | ACTL6B, SCN2A |
| membrane depolarization during action potential | 1 | 561.7× | 0.009 | SCN1A |
| neuronal action potential propagation | 1 | 468.1× | 0.009 | SCN1A |
| detection of mechanical stimulus involved in sensory perception of pain | 1 | 374.5× | 0.010 | SCN1A |
| neuromuscular process controlling posture | 1 | 351.1× | 0.010 | SCN1A |
| nerve development | 1 | 312.1× | 0.010 | SCN1A |
| neuron maturation | 1 | 267.5× | 0.011 | ACTL6B |
| regulation of G0 to G1 transition | 1 | 224.7× | 0.012 | ACTL6B |
| regulation of nucleotide-excision repair | 1 | 200.6× | 0.012 | ACTL6B |
| adult walking behavior | 1 | 165.2× | 0.013 | SCN1A |
| regulation of mitotic metaphase/anaphase transition | 1 | 165.2× | 0.013 | ACTL6B |
| positive regulation of T cell differentiation | 1 | 151.8× | 0.013 | ACTL6B |
| determination of adult lifespan | 1 | 144.0× | 0.013 | SCN1A |
| dendrite development | 1 | 130.6× | 0.013 | ACTL6B |
| positive regulation of myoblast differentiation | 1 | 122.1× | 0.013 | ACTL6B |
| positive regulation of stem cell population maintenance | 1 | 114.6× | 0.013 | ACTL6B |
| positive regulation of double-strand break repair | 1 | 114.6× | 0.013 | ACTL6B |
| regulation of G1/S transition of mitotic cell cycle | 1 | 102.1× | 0.014 | ACTL6B |
| negative regulation of cell differentiation | 1 | 95.2× | 0.015 | ACTL6B |
| positive regulation of cell differentiation | 1 | 89.2× | 0.015 | ACTL6B |
| myelination | 1 | 83.8× | 0.016 | SCN2A |
| neuron apoptotic process | 1 | 61.7× | 0.020 | SCN2A |
| memory | 1 | 61.1× | 0.020 | SCN2A |
| establishment of localization in cell | 1 | 53.5× | 0.022 | SCN1A |
| cellular response to hypoxia | 1 | 40.4× | 0.028 | SCN2A |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 1
Druggability breadth: 2 of 3 evidence-associated genes (67%) 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 |
|---|---|
| SCN1A | MEXILETINE HYDROCHLORIDE |
| SCN2A | BEPRIDIL |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| SCN2A | 99 | 4 |
| SCN1A | 94 | 4 |
| ACTL6B | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| MEXILETINE HYDROCHLORIDE | 4 | SCN1A |
| BEPRIDIL | 4 | SCN1A, SCN2A |
| DIBUCAINE | 4 | SCN1A, SCN2A |
| ARTICAINE | 4 | SCN1A, SCN2A |
| BUPIVACAINE | 4 | SCN1A, SCN2A |
| IMIPRAMINE | 4 | SCN1A, SCN2A |
| DROPERIDOL | 4 | SCN1A, SCN2A |
| DICYCLOMINE | 4 | SCN1A, SCN2A |
| TETRABENAZINE | 4 | SCN1A, SCN2A |
| PHENIRAMINE | 4 | SCN1A, SCN2A |
| PRILOCAINE | 4 | SCN1A, SCN2A |
| PROPOXYCAINE | 4 | SCN1A, SCN2A |
| PROPARACAINE | 4 | SCN1A, SCN2A |
| HEXYLCAINE | 4 | SCN1A, SCN2A |
| PRAMOXINE | 4 | SCN1A, SCN2A |
| BENOXINATE | 4 | SCN1A, SCN2A |
| QUINIDINE | 4 | SCN1A, SCN2A |
| FELODIPINE | 4 | SCN1A, SCN2A |
| PHENYTOIN | 4 | SCN1A, SCN2A |
| QUININE | 4 | SCN1A, SCN2A |
| NISOLDIPINE | 4 | SCN1A, SCN2A |
| NIFEDIPINE | 4 | SCN1A, SCN2A |
| PRAZOSIN | 4 | SCN1A, SCN2A |
| DILTIAZEM | 4 | SCN1A, SCN2A |
| PRENYLAMINE | 4 | SCN1A, SCN2A |
| COCAINE | 4 | SCN1A, SCN2A |
| TRIFLUOPERAZINE | 4 | SCN1A, SCN2A |
| CINNARIZINE | 4 | SCN1A, SCN2A |
| THIORIDAZINE | 4 | SCN1A, SCN2A |
| ETIDOCAINE | 4 | SCN1A, SCN2A |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| SCN2A | 203 | Binding:172, Functional:20, ADMET:10, Toxicity:1 |
| SCN1A | 149 | Binding:115, Functional:18, ADMET:14, Toxicity:2 |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| SCN1A | 149 |
| SCN2A | 203 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 3; 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) |
|---|---|---|
| MEXILETINE HYDROCHLORIDE | 4 | SCN1A |
| BEPRIDIL | 4 | SCN1A, SCN2A |
| DIBUCAINE | 4 | SCN1A, SCN2A |
| ARTICAINE | 4 | SCN1A, SCN2A |
| BUPIVACAINE | 4 | SCN1A, SCN2A |
| IMIPRAMINE | 4 | SCN1A, SCN2A |
| DROPERIDOL | 4 | SCN1A, SCN2A |
| DICYCLOMINE | 4 | SCN1A, SCN2A |
| TETRABENAZINE | 4 | SCN1A, SCN2A |
| PHENIRAMINE | 4 | SCN1A, SCN2A |
| PRILOCAINE | 4 | SCN1A, SCN2A |
| PROPOXYCAINE | 4 | SCN1A, SCN2A |
| PROPARACAINE | 4 | SCN1A, SCN2A |
| HEXYLCAINE | 4 | SCN1A, SCN2A |
| PRAMOXINE | 4 | SCN1A, SCN2A |
| BENOXINATE | 4 | SCN1A, SCN2A |
| QUINIDINE | 4 | SCN1A, SCN2A |
| FELODIPINE | 4 | SCN1A, SCN2A |
| PHENYTOIN | 4 | SCN1A, SCN2A |
| QUININE | 4 | SCN1A, SCN2A |
| NISOLDIPINE | 4 | SCN1A, SCN2A |
| NIFEDIPINE | 4 | SCN1A, SCN2A |
| PRAZOSIN | 4 | SCN1A, SCN2A |
| DILTIAZEM | 4 | SCN1A, SCN2A |
| PRENYLAMINE | 4 | SCN1A, SCN2A |
| COCAINE | 4 | SCN1A, SCN2A |
| TRIFLUOPERAZINE | 4 | SCN1A, SCN2A |
| CINNARIZINE | 4 | SCN1A, SCN2A |
| THIORIDAZINE | 4 | SCN1A, SCN2A |
| ETIDOCAINE | 4 | SCN1A, SCN2A |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | SCN1A, SCN2A |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | ACTL6B |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| ACTL6B | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.