Febrile seizures, familial, 4

Summary

Febrile seizures, familial, 4 (MONDO:0011443) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 216

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	febrile seizures, familial, 4
Mondo ID	MONDO:0011443
MeSH	C565788
OMIM	604352
DOID	DOID:0111305
UMLS	C1858493
MedGen	347652
Is cancer (heuristic)	no

Also known as: ADGRV1 febrile seizures, familial · FEB4 · febrile seizures, familial caused by mutation in ADGRV1 · febrile seizures, familial, 4 · febrile seizures, familial, type 4

Data availability: 216 ClinVar variants · 2 GenCC gene-disease records.

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, 4

Related subtypes (12): febrile seizures, familial, 1, febrile seizures, familial, 2, 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

216 retrieved; paginated sample, class counts are floors:

69 conflicting classifications of pathogenicity, 51 uncertain significance, 26 pathogenic/likely pathogenic, 22 likely pathogenic, 17 benign/likely benign, 13 pathogenic, 12 benign, 6 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1067661	NM_032119.4(ADGRV1):c.1239-1G>T	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075638	NM_032119.4(ADGRV1):c.2612del (p.Gly871fs)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
1075639	NM_032119.4(ADGRV1):c.14404C>T (p.Arg4802Ter)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
1098772	NM_032119.4(ADGRV1):c.9749-2del	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1371066	NM_032119.4(ADGRV1):c.11547_11550del (p.Ile3849fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1385369	NM_032119.4(ADGRV1):c.14854dup (p.His4952fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1446555	NM_032119.4(ADGRV1):c.14971C>T (p.Arg4991Ter)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
1458724	NM_032119.4(ADGRV1):c.8875C>T (p.Arg2959Ter)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
179121	NM_032119.4(ADGRV1):c.17303_17315del (p.Gly5768fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
179305	NM_032119.4(ADGRV1):c.12631C>T (p.Arg4211Ter)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
1967432	NM_032119.4(ADGRV1):c.6491-1G>A	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1969864	NM_032119.4(ADGRV1):c.4371dup (p.Thr1458fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2125215	NM_032119.4(ADGRV1):c.3364dup (p.Ser1122fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
228353	NM_032119.4(ADGRV1):c.7129C>T (p.Arg2377Ter)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265623	NM_032119.4(ADGRV1):c.10213C>T (p.Arg3405Ter)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2734742	NM_032119.4(ADGRV1):c.14455_14456del (p.Arg4819fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2734743	NM_032119.4(ADGRV1):c.17386C>T (p.Gln5796Ter)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
2852958	NM_032119.4(ADGRV1):c.12542del (p.Pro4181fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2867641	NM_032119.4(ADGRV1):c.4571C>G (p.Ser1524Ter)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3008485	NM_032119.4(ADGRV1):c.3908dup (p.Leu1303fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3014150	NM_032119.4(ADGRV1):c.582del (p.Asp195fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3641492	NM_032119.4(ADGRV1):c.2871del (p.Asn957fs)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
372373	NM_032119.4(ADGRV1):c.956dup (p.Asn319fs)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
372375	NM_032119.4(ADGRV1):c.11410C>T (p.Arg3804Ter)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
438168	NM_032119.4(ADGRV1):c.12798T>A (p.Tyr4266Ter)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
46275	NM_032119.4(ADGRV1):c.14973-2A>G	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
46306	NM_032119.4(ADGRV1):c.2398C>T (p.Arg800Ter)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
503620	NM_032119.4(ADGRV1):c.17668_17669del (p.Met5890fs)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
503694	NM_032119.4(ADGRV1):c.17062C>T (p.Arg5688Ter)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
562081	NM_032119.4(ADGRV1):c.1055C>T (p.Pro352Leu)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
ADGRV1	Moderate	Autosomal dominant	febrile seizures, familial, 4	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADGRV1	Orphanet:231178	Usher syndrome type 2
ADGRV1	Orphanet:36387	Genetic epilepsy with febrile seizure plus

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
ADGRV1	HGNC:17416	ENSG00000164199	Q8WXG9	Adhesion G-protein coupled receptor V1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADGRV1	GPCR	yes		GPCR_2_secretin-like, Calx_beta, EPTP

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
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADGRV1	196	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADGRV1	1,658

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADGRV1	Q8WXG9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	368.4×	0.008	ADGRV1
Nervous system development	1	42.9×	0.035	ADGRV1
Developmental Biology	1	14.5×	0.069	ADGRV1

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
maintenance of animal organ identity	1	3370.4×	0.003	ADGRV1
inner ear receptor cell differentiation	1	3370.4×	0.003	ADGRV1
sensory perception of light stimulus	1	1872.4×	0.003	ADGRV1
self proteolysis	1	1532.0×	0.003	ADGRV1
nervous system process	1	1203.7×	0.003	ADGRV1
detection of mechanical stimulus involved in sensory perception of sound	1	936.2×	0.003	ADGRV1
inner ear receptor cell stereocilium organization	1	842.6×	0.003	ADGRV1
establishment of protein localization	1	432.1×	0.005	ADGRV1
positive regulation of bone mineralization	1	391.9×	0.005	ADGRV1
inner ear development	1	374.5×	0.005	ADGRV1
photoreceptor cell maintenance	1	358.6×	0.005	ADGRV1
cellular response to calcium ion	1	200.6×	0.008	ADGRV1
regulation of protein stability	1	125.8×	0.012	ADGRV1
cell-cell adhesion	1	101.5×	0.013	ADGRV1
sensory perception of sound	1	100.9×	0.013	ADGRV1
visual perception	1	79.5×	0.015	ADGRV1
cell surface receptor signaling pathway	1	64.1×	0.017	ADGRV1
nervous system development	1	45.9×	0.023	ADGRV1
G protein-coupled receptor signaling pathway	1	36.2×	0.028	ADGRV1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADGRV1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

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

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)
ADGRV1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.