Febrile seizures, familial, 1

Summary

Febrile seizures, familial, 1 (MONDO:0007367) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	febrile seizures, familial, 1
Mondo ID	MONDO:0007367
MeSH	C565162
OMIM	121210
DOID	DOID:0111307
SNOMED CT	230432008
UMLS	C1852577
MedGen	338959
Is cancer (heuristic)	no

Also known as: FEB1 · febrile seizures, familial, 1

Data availability: 7 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › febrile seizures, familial › febrile seizures, familial, 1

Related subtypes (12): febrile seizures, familial, 2, febrile seizures, familial, 4, generalized epilepsy with febrile seizures plus, type 2, febrile seizures, familial, 8, febrile seizures, familial, 6, febrile seizures, familial, 5, febrile seizures, familial, 7, familial febrile seizures 9, febrile seizures, familial, 10, febrile seizures, familial, 11, febrile seizures, familial, 3a, febrile seizures, familial, 3b

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

7 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 conflicting classifications of pathogenicity, 1 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
850219	NM_001165963.4(SCN1A):c.238dup (p.Leu80fs)	SCN1A	Pathogenic	criteria provided, single submitter
961713	NM_001165963.4(SCN1A):c.2369A>T (p.Tyr790Phe)	SCN1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
158655	NM_032119.4(ADGRV1):c.9650C>T (p.Ala3217Val)	ADGRV1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
548618	NM_001365536.1(SCN9A):c.1285C>T (p.Arg429Cys)	SCN1A-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
522916	NM_032119.4(ADGRV1):c.1093G>T (p.Asp365Tyr)	ADGRV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
587575	NM_032119.4(ADGRV1):c.13537C>A (p.Pro4513Thr)	ADGRV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1052445	NM_001165963.4(SCN1A):c.5822C>A (p.Thr1941Lys)	LOC102724058	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · 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
ADGRV1	Orphanet:231178	Usher syndrome type 2
ADGRV1	Orphanet:36387	Genetic epilepsy with febrile seizure plus

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	clinvar
ADGRV1	HGNC:17416	ENSG00000164199	Q8WXG9	Adhesion G-protein coupled receptor V1	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.
ADGRV1	Adhesion G-protein coupled receptor V1	G-protein coupled receptor which has an essential role in the development of hearing and vision.

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	1	37.2×	0.080
GPCR	1	8.0×	0.180
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN1A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a1su
ADGRV1	GPCR	yes		GPCR_2_secretin-like, Calx_beta, EPTP
SCN1A-AS1	Other/Unknown	no

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	1
lateral nuclear group of thalamus	1
primary visual cortex	1
left adrenal gland	1
right adrenal gland	1
right adrenal gland 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
ADGRV1	196	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
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
ADGRV1	1,658
SCN1A-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN1A	P35498	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADGRV1	Q8WXG9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nervous system development	2	42.9×	0.005	SCN1A, ADGRV1
Interaction between L1 and Ankyrins	1	184.2×	0.010	SCN1A
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	184.2×	0.010	ADGRV1
Phase 0 - rapid depolarisation	1	173.0×	0.010	SCN1A
Developmental Biology	2	14.5×	0.010	SCN1A, ADGRV1
L1CAM interactions	1	60.1×	0.024	SCN1A
Cardiac conduction	1	54.4×	0.024	SCN1A
Muscle contraction	1	38.6×	0.029	SCN1A
Axon guidance	1	22.6×	0.044	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
maintenance of animal organ identity	1	1685.2×	0.006	ADGRV1
inner ear receptor cell differentiation	1	1685.2×	0.006	ADGRV1
sensory perception of light stimulus	1	936.2×	0.006	ADGRV1
membrane depolarization during action potential	1	842.6×	0.006	SCN1A
self proteolysis	1	766.0×	0.006	ADGRV1
neuronal action potential propagation	1	702.2×	0.006	SCN1A
nervous system process	1	601.9×	0.006	ADGRV1
detection of mechanical stimulus involved in sensory perception of pain	1	561.7×	0.006	SCN1A
neuromuscular process controlling posture	1	526.6×	0.006	SCN1A
nerve development	1	468.1×	0.006	SCN1A
detection of mechanical stimulus involved in sensory perception of sound	1	468.1×	0.006	ADGRV1
inner ear receptor cell stereocilium organization	1	421.3×	0.006	ADGRV1
cardiac muscle cell action potential involved in contraction	1	351.1×	0.007	SCN1A
adult walking behavior	1	247.8×	0.008	SCN1A
neuronal action potential	1	240.7×	0.008	SCN1A
determination of adult lifespan	1	216.1×	0.008	SCN1A
establishment of protein localization	1	216.1×	0.008	ADGRV1
positive regulation of bone mineralization	1	195.9×	0.009	ADGRV1
inner ear development	1	187.2×	0.009	ADGRV1
photoreceptor cell maintenance	1	179.3×	0.009	ADGRV1
sodium ion transport	1	135.9×	0.011	SCN1A
sodium ion transmembrane transport	1	101.5×	0.013	SCN1A
cellular response to calcium ion	1	100.3×	0.013	ADGRV1
establishment of localization in cell	1	80.2×	0.016	SCN1A
regulation of protein stability	1	62.9×	0.020	ADGRV1
cell-cell adhesion	1	50.8×	0.023	ADGRV1
sensory perception of sound	1	50.5×	0.023	ADGRV1
visual perception	1	39.8×	0.028	ADGRV1
cell surface receptor signaling pathway	1	32.0×	0.033	ADGRV1
nervous system development	1	23.0×	0.045	ADGRV1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
ADGRV1	0	0
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: 2; 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	1	ADGRV1
E	Difficult family or no structure, no drug	1	SCN1A-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ADGRV1	0	—
SCN1A-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.