developmental and epileptic encephalopathy 6B

Summary

developmental and epileptic encephalopathy 6B (MONDO:0030268) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 135

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy 6B
Mondo ID	MONDO:0030268
OMIM	619317
DOID	DOID:0070379
UMLS	C5543353
MedGen	1779648
GARD	0025526
Is cancer (heuristic)	no

Also known as: DEE6B · developmental and epileptic encephalopathy 6B · developmental and epileptic encephalopathy 6B, non-Dravet

Data availability: 135 ClinVar variants.

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 6B

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 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

135 retrieved; paginated sample, class counts are floors:

34 uncertain significance, 27 pathogenic, 27 conflicting classifications of pathogenicity, 23 pathogenic/likely pathogenic, 18 likely pathogenic, 2 benign, 2 benign/likely benign, 1 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1454054	NM_001165963.4(SCN1A):c.4322C>T (p.Ala1441Val)	LOC102724058	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
167639	NM_001165963.4(SCN1A):c.3733C>T (p.Arg1245Ter)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
1711850	NM_001165963.4(SCN1A):c.5476G>T (p.Glu1826Ter)	LOC102724058	Pathogenic	criteria provided, single submitter
189870	NM_001165963.4(SCN1A):c.4906C>T (p.Arg1636Ter)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
189881	NM_001165963.4(SCN1A):c.5536_5539del (p.Lys1846fs)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
189896	NM_001165963.4(SCN1A):c.5674C>T (p.Arg1892Ter)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
206910	NM_001165963.4(SCN1A):c.3724_3725dup (p.Asp1243fs)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
4292082	NM_001165963.4(SCN1A):c.4933C>G (p.Arg1645Gly)	LOC102724058	Pathogenic	criteria provided, single submitter
429551	NM_001165963.4(SCN1A):c.4044G>C (p.Met1348Ile)	LOC102724058	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
530440	NM_001165963.4(SCN1A):c.5263G>T (p.Asp1755Tyr)	LOC102724058	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
68533	NM_001165963.4(SCN1A):c.3734G>A (p.Arg1245Gln)	LOC102724058	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
68559	NM_001165963.4(SCN1A):c.4970G>A (p.Arg1657His)	LOC102724058	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
68570	NM_001165963.4(SCN1A):c.5347G>A (p.Ala1783Thr)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
1057080	NM_001165963.4(SCN1A):c.1169T>C (p.Leu390Pro)	SCN1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098587	NM_001165963.4(SCN1A):c.1264G>T (p.Val422Leu)	SCN1A	Pathogenic	no assertion criteria provided
1179015	NM_001165963.4(SCN1A):c.2846G>A (p.Cys949Tyr)	SCN1A	Pathogenic	criteria provided, multiple submitters, no conflicts
12889	NM_001165963.4(SCN1A):c.664C>T (p.Arg222Ter)	SCN1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12896	NM_001165963.4(SCN1A):c.434T>C (p.Met145Thr)	SCN1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1323556	NM_001165963.4(SCN1A):c.840G>A (p.Trp280Ter)	SCN1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1418113	NM_001165963.4(SCN1A):c.811G>A (p.Gly271Ser)	SCN1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1515913	NM_001165963.4(SCN1A):c.602+1del	SCN1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1683549	NM_001165963.4(SCN1A):c.1303del (p.Glu435fs)	SCN1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686141	NM_001165963.4(SCN1A):c.5005G>A (p.Ala1669Thr)	SCN1A	Pathogenic	criteria provided, multiple submitters, no conflicts
189938	NM_001165963.4(SCN1A):c.2589+3A>T	SCN1A	Pathogenic	criteria provided, multiple submitters, no conflicts
197187	NM_001165963.4(SCN1A):c.602+1G>A	SCN1A	Pathogenic	criteria provided, multiple submitters, no conflicts
206787	NM_001165963.4(SCN1A):c.2782C>T (p.Gln928Ter)	SCN1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
206914	NM_001165963.4(SCN1A):c.141del (p.Asn47fs)	SCN1A	Pathogenic	criteria provided, multiple submitters, no conflicts
206933	NM_001165963.4(SCN1A):c.985G>T (p.Gly329Cys)	SCN1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2430163	NM_001165963.4(SCN1A):c.2589+2dup	SCN1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2446437	NM_001165963.4(SCN1A):c.1171-1G>A	SCN1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	clinvar
SCN1A-AS1	HGNC:54069	ENSG00000236107		SCN1A and SCN9A antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	55.8×	0.036
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN1A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a1su
SCN1A-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
lateral nuclear group of thalamus	1
primary visual cortex	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN1A	154	tissue_specific	marker	Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex
SCN1A-AS1	129	tissue_specific	marker	sural nerve, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN1A	2,287
SCN1A-AS1	0

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN1A	P35498	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (1 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 1 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	1	368.4×	0.012	SCN1A
Phase 0 - rapid depolarisation	1	346.1×	0.012	SCN1A
L1CAM interactions	1	120.2×	0.018	SCN1A
Cardiac conduction	1	108.8×	0.018	SCN1A
Muscle contraction	1	77.2×	0.021	SCN1A
Axon guidance	1	45.1×	0.027	SCN1A
Nervous system development	1	42.9×	0.027	SCN1A
Developmental Biology	1	14.5×	0.069	SCN1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
membrane depolarization during action potential	1	1685.2×	0.003	SCN1A
neuronal action potential propagation	1	1404.3×	0.003	SCN1A
detection of mechanical stimulus involved in sensory perception of pain	1	1123.5×	0.003	SCN1A
neuromuscular process controlling posture	1	1053.2×	0.003	SCN1A
nerve development	1	936.2×	0.003	SCN1A
cardiac muscle cell action potential involved in contraction	1	702.2×	0.003	SCN1A
adult walking behavior	1	495.6×	0.003	SCN1A
neuronal action potential	1	481.5×	0.003	SCN1A
determination of adult lifespan	1	432.1×	0.003	SCN1A
sodium ion transport	1	271.8×	0.004	SCN1A
sodium ion transmembrane transport	1	203.0×	0.005	SCN1A
establishment of localization in cell	1	160.5×	0.006	SCN1A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 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
SCN1A	MEXILETINE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN1A	94	4
SCN1A-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MEXILETINE HYDROCHLORIDE	4	SCN1A
BEPRIDIL	4	SCN1A
DIBUCAINE	4	SCN1A
ARTICAINE	4	SCN1A
BUPIVACAINE	4	SCN1A
IMIPRAMINE	4	SCN1A
DROPERIDOL	4	SCN1A
DICYCLOMINE	4	SCN1A
TETRABENAZINE	4	SCN1A
PHENIRAMINE	4	SCN1A
PRILOCAINE	4	SCN1A
PROPOXYCAINE	4	SCN1A
PROPARACAINE	4	SCN1A
HEXYLCAINE	4	SCN1A
PRAMOXINE	4	SCN1A
BENOXINATE	4	SCN1A
QUINIDINE	4	SCN1A
FELODIPINE	4	SCN1A
PHENYTOIN	4	SCN1A
QUININE	4	SCN1A
NISOLDIPINE	4	SCN1A
NIFEDIPINE	4	SCN1A
PRAZOSIN	4	SCN1A
DILTIAZEM	4	SCN1A
PRENYLAMINE	4	SCN1A
COCAINE	4	SCN1A
TRIFLUOPERAZINE	4	SCN1A
CINNARIZINE	4	SCN1A
THIORIDAZINE	4	SCN1A
ETIDOCAINE	4	SCN1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
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

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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
DIBUCAINE	4	SCN1A
ARTICAINE	4	SCN1A
BUPIVACAINE	4	SCN1A
IMIPRAMINE	4	SCN1A
DROPERIDOL	4	SCN1A
DICYCLOMINE	4	SCN1A
TETRABENAZINE	4	SCN1A
PHENIRAMINE	4	SCN1A
PRILOCAINE	4	SCN1A
PROPOXYCAINE	4	SCN1A
PROPARACAINE	4	SCN1A
HEXYLCAINE	4	SCN1A
PRAMOXINE	4	SCN1A
BENOXINATE	4	SCN1A
QUINIDINE	4	SCN1A
FELODIPINE	4	SCN1A
PHENYTOIN	4	SCN1A
QUININE	4	SCN1A
NISOLDIPINE	4	SCN1A
NIFEDIPINE	4	SCN1A
PRAZOSIN	4	SCN1A
DILTIAZEM	4	SCN1A
PRENYLAMINE	4	SCN1A
COCAINE	4	SCN1A
TRIFLUOPERAZINE	4	SCN1A
CINNARIZINE	4	SCN1A
THIORIDAZINE	4	SCN1A
ETIDOCAINE	4	SCN1A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCN1A
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	SCN1A-AS1

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)
SCN1A-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.