Seizures, benign familial infantile, 2

Summary

Seizures, benign familial infantile, 2 (MONDO:0011593) is a disease caused by PRRT2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: PRRT2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 49

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	seizures, benign familial infantile, 2
Mondo ID	MONDO:0011593
MeSH	C565296
OMIM	605751
DOID	DOID:0081115
UMLS	C1853995
MedGen	381313
GARD	0016504
Is cancer (heuristic)	no

Also known as: BFIS2 · seizures, benign familial infantile, 2 · seizures, benign familial infantile, type 2

Data availability: 49 ClinVar variants · 2 GenCC gene-disease records.

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 › seizures, benign familial infantile, 2

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

49 retrieved; paginated sample, class counts are floors:

13 pathogenic, 9 conflicting classifications of pathogenicity, 9 pathogenic/likely pathogenic, 7 likely pathogenic, 4 uncertain significance, 4 benign/likely benign, 2 likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1694791	NM_145239.3(PRRT2):c.250del (p.Ala84fs)	MVP-DT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2627914	NM_145239.3(PRRT2):c.284C>A (p.Ser95Ter)	MVP-DT	Pathogenic	criteria provided, multiple submitters, no conflicts
31171	NM_145239.3(PRRT2):c.629dup (p.Ala211fs)	MVP-DT	Pathogenic	criteria provided, multiple submitters, no conflicts
31174	NM_145239.3(PRRT2):c.718C>T (p.Arg240Ter)	MVP-DT	Pathogenic	criteria provided, multiple submitters, no conflicts
39752	NM_145239.3(PRRT2):c.649del (p.Arg217fs)	MVP-DT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39754	NM_145239.3(PRRT2):c.629del (p.Pro210fs)	MVP-DT	Pathogenic	criteria provided, multiple submitters, no conflicts
39756	NM_145239.3(PRRT2):c.748C>T (p.Gln250Ter)	MVP-DT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4530616	NM_145239.3(PRRT2):c.433del (p.Arg145fs)	MVP-DT	Pathogenic	criteria provided, single submitter
468617	NM_145239.3(PRRT2):c.649C>T (p.Arg217Ter)	MVP-DT	Pathogenic	criteria provided, multiple submitters, no conflicts
4796525	NM_145239.3(PRRT2):c.766del (p.Val256fs)	MVP-DT	Pathogenic	criteria provided, single submitter
65758	NM_145239.3(PRRT2):c.649dup (p.Arg217fs)	MVP-DT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
871891	NM_145239.3(PRRT2):c.971dup (p.Val325fs)	MVP-DT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
932548	NM_145239.3(PRRT2):c.880-34G>A	MVP-DT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333727	NM_145239.3(PRRT2):c.-65-1G>A	PRRT2	Pathogenic	criteria provided, single submitter
1802974	NM_145239.3(PRRT2):c.397del (p.Glu133fs)	PRRT2	Pathogenic	no assertion criteria provided
1809610	NM_145239.3(PRRT2):c.46G>T (p.Glu16Ter)	PRRT2	Pathogenic	no assertion criteria provided
183020	NM_145239.3(PRRT2):c.650del (p.Arg217fs)	PRRT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2504178	NM_145239.3(PRRT2):c.640delinsCC (p.Ala214fs)	PRRT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31173	NM_145239.3(PRRT2):c.879+5G>A	PRRT2	Pathogenic	no assertion criteria provided
3580043	NM_145239.3(PRRT2):c.107_110del (p.Gln36fs)	PRRT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39755	NM_145239.3(PRRT2):c.291del (p.Asn98fs)	PRRT2	Pathogenic	no assertion criteria provided
813798	NC_000016.10:g.(?29813054)(29813955_?)del	PRRT2	Pathogenic	criteria provided, single submitter
2500700	NM_145239.3(PRRT2):c.1001T>A (p.Ile334Asn)	MVP-DT	Likely pathogenic	criteria provided, single submitter
626000	NM_145239.3(PRRT2):c.304del (p.Glu102fs)	MVP-DT	Likely pathogenic	criteria provided, single submitter
813802	NM_145239.3(PRRT2):c.835C>G (p.Pro279Ala)	MVP-DT	Likely pathogenic	criteria provided, single submitter
1707531	NM_145239.3(PRRT2):c.914G>A (p.Gly305Glu)	PRRT2	Likely pathogenic	criteria provided, single submitter
1709866	NM_145239.3(PRRT2):c.515_516del (p.Leu171_Ser172insTer)	PRRT2	Likely pathogenic	criteria provided, single submitter
4796776	NM_145239.3(PRRT2):c.827G>A (p.Cys276Tyr)	PRRT2	Likely pathogenic	criteria provided, single submitter
976325	NM_145239.3(PRRT2):c.341_342del (p.Val114fs)	PRRT2	Likely pathogenic	criteria provided, single submitter
130039	NM_145239.3(PRRT2):c.67G>A (p.Glu23Lys)	MVP-DT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 6 · 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
PRRT2	Definitive	Autosomal dominant	infantile convulsions and choreoathetosis	18

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRRT2	Orphanet:306	Self-limited infantile epilepsy
PRRT2	Orphanet:36387	Genetic epilepsy with febrile seizure plus
PRRT2	Orphanet:569	Familial or sporadic hemiplegic migraine
PRRT2	Orphanet:98809	Paroxysmal kinesigenic dyskinesia
PRRT2	Orphanet:98810	Paroxysmal non-kinesigenic dyskinesia
PRRT2	Orphanet:98811	Paroxysmal exertion-induced dyskinesia

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
PRRT2	HGNC:30500	ENSG00000167371	Q7Z6L0	Proline-rich transmembrane protein 2	gencc,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)
PRRT2	Proline-rich transmembrane protein 2	As a component of the outer core of AMPAR complex, may be involved in synaptic transmission in the central nervous system.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRRT2	Other/Unknown	no		CD225/Dispanin_fam, CD225/Dispanin
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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	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
PRRT2	202	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
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
PRRT2	1,545
MVP-DT	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRRT2	Q7Z6L0	51.86

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

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
negative regulation of short-term synaptic potentiation	1	16852.0×	3e-04	PRRT2
negative regulation of SNARE complex assembly	1	8426.0×	3e-04	PRRT2
regulation of calcium-dependent activation of synaptic vesicle fusion	1	5617.3×	3e-04	PRRT2
synaptic vesicle fusion to presynaptic active zone membrane	1	1685.2×	7e-04	PRRT2
neuromuscular process controlling posture	1	1053.2×	9e-04	PRRT2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
PRRT2	0	0
MVP-DT	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	0
E	Difficult family or no structure, no drug	2	PRRT2, MVP-DT

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)
PRRT2	0	—
MVP-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.