Developmental and epileptic encephalopathy, 62

Summary

Developmental and epileptic encephalopathy, 62 (MONDO:0033371) is a disease caused by SCN3A (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SCN3A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 92

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 62
Mondo ID	MONDO:0033371
OMIM	617938
DOID	DOID:0080420
UMLS	C4693699
MedGen	1631233
GARD	0016271
Is cancer (heuristic)	no

Also known as: DEE62 · developmental and epileptic encephalopathy 62 · EIEE62 · epileptic encephalopathy, early infantile, 62

Data availability: 92 ClinVar variants · 1 GenCC gene-disease record.

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, 62

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, 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, 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

92 retrieved; paginated sample, class counts are floors:

50 uncertain significance, 13 likely pathogenic, 10 benign, 10 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 3 benign/likely benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1329934	NM_006922.4(SCN3A):c.4457C>T (p.Thr1486Ile)	SCN3A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1329938	NM_006922.4(SCN3A):c.5295G>A (p.Met1765Ile)	SCN3A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1802268	NM_006922.4(SCN3A):c.2017G>T (p.Glu673Ter)	SCN3A	Pathogenic	criteria provided, single submitter
373960	NM_006922.4(SCN3A):c.2624T>C (p.Ile875Thr)	SCN3A	Pathogenic	reviewed by expert panel
379838	NM_006922.4(SCN3A):c.3998C>T (p.Pro1333Leu)	SCN3A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
432534	NM_006922.4(SCN3A):c.4862G>A (p.Arg1621Gln)	SCN3A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1320056	NM_006922.4(SCN3A):c.5621T>G (p.Met1874Arg)	SCN3A	Likely pathogenic	criteria provided, single submitter
1329932	NM_006922.4(SCN3A):c.2564T>C (p.Leu855Pro)	SCN3A	Likely pathogenic	criteria provided, single submitter
1329933	NM_006922.4(SCN3A):c.2653C>T (p.Leu885Phe)	SCN3A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1329935	NM_006922.4(SCN3A):c.4518del (p.Lys1506fs)	SCN3A	Likely pathogenic	criteria provided, single submitter
1329936	NM_006922.4(SCN3A):c.4937T>C (p.Phe1646Ser)	SCN3A	Likely pathogenic	criteria provided, single submitter
1329937	NM_006922.4(SCN3A):c.5006A>G (p.Tyr1669Cys)	SCN3A	Likely pathogenic	criteria provided, single submitter
3063575	NM_006922.4(SCN3A):c.694+2T>G	SCN3A	Likely pathogenic	criteria provided, single submitter
3367041	NM_006922.4(SCN3A):c.4431+1A>G	SCN3A	Likely pathogenic	criteria provided, single submitter
431726	NM_006922.4(SCN3A):c.626T>C (p.Leu209Pro)	SCN3A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4813627	NM_006922.4(SCN3A):c.2565+1G>C	SCN3A	Likely pathogenic	criteria provided, single submitter
521063	NM_006922.4(SCN3A):c.5306T>C (p.Val1769Ala)	SCN3A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
801773	NM_006922.4(SCN3A):c.2947TTG[1] (p.Leu984del)	SCN3A	Likely pathogenic	criteria provided, single submitter
808839	NM_006922.4(SCN3A):c.4403T>G (p.Ile1468Arg)	SCN3A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1320212	NM_006922.4(SCN3A):c.694+1G>T	SCN3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1485226	NM_006922.4(SCN3A):c.1840C>G (p.Pro614Ala)	SCN3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1806345	NM_006922.4(SCN3A):c.4484C>T (p.Ala1495Val)	SCN3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194238	NM_006922.4(SCN3A):c.2003G>A (p.Gly668Glu)	SCN3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194858	NM_006922.4(SCN3A):c.3253A>G (p.Ile1085Val)	SCN3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3062221	NM_006922.4(SCN3A):c.1945dup (p.Asp649fs)	SCN3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
641086	NM_006922.4(SCN3A):c.4712G>C (p.Gly1571Ala)	SCN3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
644906	NM_006922.4(SCN3A):c.1748G>A (p.Arg583Gln)	SCN3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
859687	NM_006922.4(SCN3A):c.560G>A (p.Arg187His)	SCN3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
859810	NM_006922.4(SCN3A):c.4236A>G (p.Gln1412=)	SCN3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1038181	NM_006922.4(SCN3A):c.1670A>T (p.Gln557Leu)	SCN3A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
SCN3A	Definitive	Autosomal dominant	genetic developmental and epileptic encephalopathy	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN3A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SCN3A	Orphanet:98820	Familial focal epilepsy with variable foci

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN3A	HGNC:10590	ENSG00000153253	Q9NY46	Sodium channel protein type 3 subunit alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN3A	Sodium channel protein type 3 subunit alpha	Pore-forming subunit of Nav1.3, 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: 0 · Druggable fraction: 1.0

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	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN3A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
endothelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN3A	221	broad	marker	endothelial cell, cortical plate, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN3A	1,454

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN3A	Q9NY46	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 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×	0.010	SCN3A
Phase 0 - rapid depolarisation	1	346.1×	0.010	SCN3A
Sensory perception of taste	1	335.9×	0.010	SCN3A
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	278.5×	0.010	SCN3A
L1CAM interactions	1	120.2×	0.017	SCN3A
Cardiac conduction	1	108.8×	0.017	SCN3A
Sensory Perception	1	95.2×	0.017	SCN3A
Muscle contraction	1	77.2×	0.018	SCN3A
Axon guidance	1	45.1×	0.026	SCN3A
Nervous system development	1	42.9×	0.026	SCN3A
Developmental Biology	1	14.5×	0.069	SCN3A

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×	0.002	SCN3A
behavioral response to pain	1	887.0×	0.002	SCN3A
cardiac muscle cell action potential involved in contraction	1	702.2×	0.002	SCN3A
sodium ion transport	1	271.8×	0.005	SCN3A
sodium ion transmembrane transport	1	203.0×	0.005	SCN3A

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
SCN3A	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN3A	93	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN3A
DIBUCAINE	4	SCN3A
ARTICAINE	4	SCN3A
BUPIVACAINE	4	SCN3A
IMIPRAMINE	4	SCN3A
DROPERIDOL	4	SCN3A
DICYCLOMINE	4	SCN3A
TETRABENAZINE	4	SCN3A
PHENIRAMINE	4	SCN3A
PRILOCAINE	4	SCN3A
PROPOXYCAINE	4	SCN3A
PROPARACAINE	4	SCN3A
HEXYLCAINE	4	SCN3A
PRAMOXINE	4	SCN3A
BENOXINATE	4	SCN3A
QUINIDINE	4	SCN3A
FELODIPINE	4	SCN3A
PHENYTOIN	4	SCN3A
QUININE	4	SCN3A
NISOLDIPINE	4	SCN3A
NIFEDIPINE	4	SCN3A
PRAZOSIN	4	SCN3A
DILTIAZEM	4	SCN3A
PRENYLAMINE	4	SCN3A
COCAINE	4	SCN3A
TRIFLUOPERAZINE	4	SCN3A
CINNARIZINE	4	SCN3A
THIORIDAZINE	4	SCN3A
ETIDOCAINE	4	SCN3A
CHLORPHENIRAMINE	4	SCN3A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCN3A	102	Binding:79, Functional:18, ADMET:4, Toxicity:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN3A	102

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)
BEPRIDIL	4	SCN3A
DIBUCAINE	4	SCN3A
ARTICAINE	4	SCN3A
BUPIVACAINE	4	SCN3A
IMIPRAMINE	4	SCN3A
DROPERIDOL	4	SCN3A
DICYCLOMINE	4	SCN3A
TETRABENAZINE	4	SCN3A
PHENIRAMINE	4	SCN3A
PRILOCAINE	4	SCN3A
PROPOXYCAINE	4	SCN3A
PROPARACAINE	4	SCN3A
HEXYLCAINE	4	SCN3A
PRAMOXINE	4	SCN3A
BENOXINATE	4	SCN3A
QUINIDINE	4	SCN3A
FELODIPINE	4	SCN3A
PHENYTOIN	4	SCN3A
QUININE	4	SCN3A
NISOLDIPINE	4	SCN3A
NIFEDIPINE	4	SCN3A
PRAZOSIN	4	SCN3A
DILTIAZEM	4	SCN3A
PRENYLAMINE	4	SCN3A
COCAINE	4	SCN3A
TRIFLUOPERAZINE	4	SCN3A
CINNARIZINE	4	SCN3A
THIORIDAZINE	4	SCN3A
ETIDOCAINE	4	SCN3A
CHLORPHENIRAMINE	4	SCN3A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCN3A
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.