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Atlas / Disease / Epilepsy, familial focal, with variable foci 4

Epilepsy, familial focal, with variable foci 4

disease
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Also known as FFEVF4

Summary

Epilepsy, familial focal, with variable foci 4 (MONDO:0054776) 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: 71

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameepilepsy, familial focal, with variable foci 4
Mondo IDMONDO:0054776
OMIM617935
DOIDDOID:0081424
UMLSC4693694
MedGen1644614
GARD0025973
Is cancer (heuristic)no

Also known as: FFEVF4

Data availability: 71 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › focal epilepsy › familial partial epilepsy › familial focal epilepsy with variable foci › epilepsy, familial focal, with variable foci 4

Related subtypes (3): epilepsy, familial focal, with variable foci 2, epilepsy, familial focal, with variable foci 3, epilepsy, familial focal, with variable foci 1

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

71 retrieved; paginated sample, class counts are floors:

44 uncertain significance, 10 benign, 7 conflicting classifications of pathogenicity, 4 pathogenic, 3 benign/likely benign, 1 pathogenic/likely pathogenic, 1 likely pathogenic, 1 likely benign

ClinVarVariant (HGVS)GeneClassificationReview
1329938NM_006922.4(SCN3A):c.5295G>A (p.Met1765Ile)SCN3APathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1802268NM_006922.4(SCN3A):c.2017G>T (p.Glu673Ter)SCN3APathogeniccriteria provided, single submitter
373960NM_006922.4(SCN3A):c.2624T>C (p.Ile875Thr)SCN3APathogenicreviewed by expert panel
4819726NM_006922.4(SCN3A):c.3393+2T>GSCN3APathogeniccriteria provided, single submitter
522566NM_006922.3(SCN3A):c.742T>C (p.Ser248Pro)SCN3APathogenicno assertion criteria provided
4293969NM_006922.4(SCN3A):c.19del (p.Val7fs)SCN3ALikely pathogeniccriteria provided, single submitter
194238NM_006922.4(SCN3A):c.2003G>A (p.Gly668Glu)SCN3AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
194858NM_006922.4(SCN3A):c.3253A>G (p.Ile1085Val)SCN3AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
403870NM_006922.4(SCN3A):c.791T>C (p.Ile264Thr)SCN3AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
522563NM_006922.4(SCN3A):c.1070G>A (p.Arg357Gln)SCN3AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
859687NM_006922.4(SCN3A):c.560G>A (p.Arg187His)SCN3AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
859810NM_006922.4(SCN3A):c.4236A>G (p.Gln1412=)SCN3AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
944297NM_006922.4(SCN3A):c.3682A>G (p.Ile1228Val)SCN3AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1008548NM_006922.4(SCN3A):c.3133A>G (p.Ile1045Val)SCN3AUncertain significancecriteria provided, multiple submitters, no conflicts
1019843NM_006922.4(SCN3A):c.694+3G>TSCN3AUncertain significancecriteria provided, single submitter
1033165NM_006922.4(SCN3A):c.1580A>C (p.Glu527Ala)SCN3AUncertain significancecriteria provided, single submitter
1062741NM_006922.4(SCN3A):c.3629C>T (p.Thr1210Ile)SCN3AUncertain significancecriteria provided, multiple submitters, no conflicts
1342364NM_006922.4(SCN3A):c.1663C>A (p.Pro555Thr)SCN3AUncertain significancecriteria provided, single submitter
1422176NM_006922.4(SCN3A):c.4G>A (p.Ala2Thr)SCN3AUncertain significancecriteria provided, multiple submitters, no conflicts
1480919NM_006922.4(SCN3A):c.83G>A (p.Arg28His)SCN3AUncertain significancecriteria provided, multiple submitters, no conflicts
1491713NM_006922.4(SCN3A):c.5612G>A (p.Arg1871Gln)SCN3AUncertain significancecriteria provided, multiple submitters, no conflicts
1675128NM_006922.4(SCN3A):c.5734A>C (p.Arg1912=)SCN3AUncertain significancecriteria provided, single submitter
1679624NM_006922.4(SCN3A):c.-50-2312T>CSCN3AUncertain significancecriteria provided, single submitter
1708494NM_006922.4(SCN3A):c.603-119C>TSCN3AUncertain significancecriteria provided, single submitter
1803147NM_006922.4(SCN3A):c.595G>A (p.Val199Met)SCN3AUncertain significancecriteria provided, single submitter
1878573NM_006922.4(SCN3A):c.5047G>T (p.Glu1683Ter)SCN3AUncertain significancecriteria provided, single submitter
1878603NM_006922.4(SCN3A):c.3683T>C (p.Ile1228Thr)SCN3AUncertain significancecriteria provided, multiple submitters, no conflicts
2042360NM_006922.4(SCN3A):c.764T>C (p.Val255Ala)SCN3AUncertain significancecriteria provided, multiple submitters, no conflicts
2067945NM_006922.4(SCN3A):c.2285T>C (p.Val762Ala)SCN3AUncertain significancecriteria provided, multiple submitters, no conflicts
240708NM_006922.4(SCN3A):c.2021G>A (p.Gly674Asp)SCN3AUncertain significancecriteria provided, multiple submitters, no conflicts

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.

GeneClassificationInheritanceDiseaseRecords
SCN3AStrongAutosomal dominantepilepsy, familial focal, with variable foci 47

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SCN3AOrphanet:442835Non-specific early-onset epileptic encephalopathy
SCN3AOrphanet:98820Familial focal epilepsy with variable foci

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SCN3AHGNC:10590ENSG00000153253Q9NY46Sodium channel protein type 3 subunit alphagencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SCN3ASodium channel protein type 3 subunit alphaPore-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.

FamilyGenesFoldFDR
Ion channel1111.5×0.009

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SCN3AIon channelyesNa_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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
cortical plate1
endothelial cell1
middle temporal gyrus1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SCN3A221broadmarkerendothelial cell, cortical plate, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
SCN3A1,454

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
SCN3AQ9NY462

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.

PathwayCohort genesFoldFDRSample cohort genes
Interaction between L1 and Ankyrins1368.4×0.010SCN3A
Phase 0 - rapid depolarisation1346.1×0.010SCN3A
Sensory perception of taste1335.9×0.010SCN3A
Sensory perception of sweet, bitter, and umami (glutamate) taste1278.5×0.010SCN3A
L1CAM interactions1120.2×0.017SCN3A
Cardiac conduction1108.8×0.017SCN3A
Sensory Perception195.2×0.017SCN3A
Muscle contraction177.2×0.018SCN3A
Axon guidance145.1×0.026SCN3A
Nervous system development142.9×0.026SCN3A
Developmental Biology114.5×0.069SCN3A

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 termCohort genesFoldFDRSample cohort genes
membrane depolarization during action potential11685.2×0.002SCN3A
behavioral response to pain1887.0×0.002SCN3A
cardiac muscle cell action potential involved in contraction1702.2×0.002SCN3A
sodium ion transport1271.8×0.005SCN3A
sodium ion transmembrane transport1203.0×0.005SCN3A

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.

SymbolExample approved molecule
SCN3ABEPRIDIL

Top cohort targets by molecule count

SymbolMoleculesMax phase
SCN3A934

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
BEPRIDIL4SCN3A
DIBUCAINE4SCN3A
ARTICAINE4SCN3A
BUPIVACAINE4SCN3A
IMIPRAMINE4SCN3A
DROPERIDOL4SCN3A
DICYCLOMINE4SCN3A
TETRABENAZINE4SCN3A
PHENIRAMINE4SCN3A
PRILOCAINE4SCN3A
PROPOXYCAINE4SCN3A
PROPARACAINE4SCN3A
HEXYLCAINE4SCN3A
PRAMOXINE4SCN3A
BENOXINATE4SCN3A
QUINIDINE4SCN3A
FELODIPINE4SCN3A
PHENYTOIN4SCN3A
QUININE4SCN3A
NISOLDIPINE4SCN3A
NIFEDIPINE4SCN3A
PRAZOSIN4SCN3A
DILTIAZEM4SCN3A
PRENYLAMINE4SCN3A
COCAINE4SCN3A
TRIFLUOPERAZINE4SCN3A
CINNARIZINE4SCN3A
THIORIDAZINE4SCN3A
ETIDOCAINE4SCN3A
CHLORPHENIRAMINE4SCN3A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
SCN3A102Binding: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.

SymbolChEMBL assays
SCN3A102

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.

CompoundMax phaseCohort target (bioactivity)
BEPRIDIL4SCN3A
DIBUCAINE4SCN3A
ARTICAINE4SCN3A
BUPIVACAINE4SCN3A
IMIPRAMINE4SCN3A
DROPERIDOL4SCN3A
DICYCLOMINE4SCN3A
TETRABENAZINE4SCN3A
PHENIRAMINE4SCN3A
PRILOCAINE4SCN3A
PROPOXYCAINE4SCN3A
PROPARACAINE4SCN3A
HEXYLCAINE4SCN3A
PRAMOXINE4SCN3A
BENOXINATE4SCN3A
QUINIDINE4SCN3A
FELODIPINE4SCN3A
PHENYTOIN4SCN3A
QUININE4SCN3A
NISOLDIPINE4SCN3A
NIFEDIPINE4SCN3A
PRAZOSIN4SCN3A
DILTIAZEM4SCN3A
PRENYLAMINE4SCN3A
COCAINE4SCN3A
TRIFLUOPERAZINE4SCN3A
CINNARIZINE4SCN3A
THIORIDAZINE4SCN3A
ETIDOCAINE4SCN3A
CHLORPHENIRAMINE4SCN3A

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1SCN3A
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

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.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 69

This page pulls from 69 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot