Benign familial neonatal-infantile seizures 1

Summary

Benign familial neonatal-infantile seizures 1 (MONDO:0042499) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	benign familial neonatal-infantile seizures 1
Mondo ID	MONDO:0042499
OMIM	601764
DOID	DOID:0081114
UMLS	C4551769
MedGen	1638448
GARD	0000856
Is cancer (heuristic)	no

Also known as: benign familial infantile convulsions syndrome · benign infantile familial convulsions · BFIC1 · BFIS1 · seizures, benign familial infantile, 1

Data availability: 3 ClinVar variants.

Disease family

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

Related subtypes (4): seizures, benign familial infantile, 2, seizures, benign familial infantile, 3, seizures, benign familial infantile, 4, seizures, benign familial infantile, 5

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

3 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
39752	NM_145239.3(PRRT2):c.649del (p.Arg217fs)	MVP-DT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
206999	NM_001040142.2(SCN2A):c.4264A>G (p.Lys1422Glu)	SCN2A	Pathogenic	criteria provided, single submitter
392633	NM_001040142.2(SCN2A):c.2767T>C (p.Trp923Arg)	SCN2A	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN2A	HGNC:10588	ENSG00000136531	Q99250	Sodium channel protein type 2 subunit alpha	clinvar
MVP-DT	HGNC:56029	ENSG00000238045		MVP divergent transcript	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN2A	Sodium channel protein type 2 subunit alpha	Mediates the voltage-dependent sodium ion permeability of 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)
SCN2A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
MVP-DT	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
cerebellar vermis	1
middle temporal gyrus	1
mucosa of transverse colon	1
oviduct epithelium	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN2A	187	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis
MVP-DT	191		marker	oviduct epithelium, mucosa of transverse colon, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN2A	2,810
MVP-DT	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN2A	Q99250	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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×	0.010	SCN2A
Phase 0 - rapid depolarisation	1	346.1×	0.010	SCN2A
Sensory perception of taste	1	335.9×	0.010	SCN2A
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	278.5×	0.010	SCN2A
L1CAM interactions	1	120.2×	0.017	SCN2A
Cardiac conduction	1	108.8×	0.017	SCN2A
Sensory Perception	1	95.2×	0.017	SCN2A
Muscle contraction	1	77.2×	0.018	SCN2A
Axon guidance	1	45.1×	0.026	SCN2A
Nervous system development	1	42.9×	0.026	SCN2A
Developmental Biology	1	14.5×	0.069	SCN2A

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
intrinsic apoptotic signaling pathway in response to osmotic stress	1	8426.0×	0.001	SCN2A
cardiac muscle cell action potential involved in contraction	1	702.2×	0.007	SCN2A
neuronal action potential	1	481.5×	0.007	SCN2A
sodium ion transport	1	271.8×	0.007	SCN2A
myelination	1	251.5×	0.007	SCN2A
sodium ion transmembrane transport	1	203.0×	0.007	SCN2A
neuron apoptotic process	1	185.2×	0.007	SCN2A
memory	1	183.2×	0.007	SCN2A
cellular response to hypoxia	1	121.2×	0.009	SCN2A
nervous system development	1	45.9×	0.022	SCN2A

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
SCN2A	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN2A	99	4
MVP-DT	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A
BUPIVACAINE	4	SCN2A
IMIPRAMINE	4	SCN2A
DROPERIDOL	4	SCN2A
DICYCLOMINE	4	SCN2A
TETRABENAZINE	4	SCN2A
PHENIRAMINE	4	SCN2A
PRILOCAINE	4	SCN2A
PROPOXYCAINE	4	SCN2A
PROPARACAINE	4	SCN2A
HEXYLCAINE	4	SCN2A
PRAMOXINE	4	SCN2A
BENOXINATE	4	SCN2A
QUINIDINE	4	SCN2A
FELODIPINE	4	SCN2A
PHENYTOIN	4	SCN2A
QUININE	4	SCN2A
NISOLDIPINE	4	SCN2A
NIFEDIPINE	4	SCN2A
PRAZOSIN	4	SCN2A
DILTIAZEM	4	SCN2A
PRENYLAMINE	4	SCN2A
COCAINE	4	SCN2A
TRIFLUOPERAZINE	4	SCN2A
CINNARIZINE	4	SCN2A
THIORIDAZINE	4	SCN2A
ETIDOCAINE	4	SCN2A
CHLORPHENIRAMINE	4	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

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN2A	203

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	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A
BUPIVACAINE	4	SCN2A
IMIPRAMINE	4	SCN2A
DROPERIDOL	4	SCN2A
DICYCLOMINE	4	SCN2A
TETRABENAZINE	4	SCN2A
PHENIRAMINE	4	SCN2A
PRILOCAINE	4	SCN2A
PROPOXYCAINE	4	SCN2A
PROPARACAINE	4	SCN2A
HEXYLCAINE	4	SCN2A
PRAMOXINE	4	SCN2A
BENOXINATE	4	SCN2A
QUINIDINE	4	SCN2A
FELODIPINE	4	SCN2A
PHENYTOIN	4	SCN2A
QUININE	4	SCN2A
NISOLDIPINE	4	SCN2A
NIFEDIPINE	4	SCN2A
PRAZOSIN	4	SCN2A
DILTIAZEM	4	SCN2A
PRENYLAMINE	4	SCN2A
COCAINE	4	SCN2A
TRIFLUOPERAZINE	4	SCN2A
CINNARIZINE	4	SCN2A
THIORIDAZINE	4	SCN2A
ETIDOCAINE	4	SCN2A
CHLORPHENIRAMINE	4	SCN2A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	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	MVP-DT

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)
MVP-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.