Generalized epilepsy with febrile seizures plus, type 12

disease

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Summary

Generalized epilepsy with febrile seizures plus, type 12 (MONDO:0958324) is a disease caused by SLC32A1 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: SLC32A1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	generalized epilepsy with febrile seizures plus, type 12
Mondo ID	MONDO:0958324
OMIM	620755
UMLS	C5935592
MedGen	1854923
GARD	0027006
Is cancer (heuristic)	no

Data availability: 8 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › hereditary generalized epilepsy › generalized epilepsy with febrile seizures plus › generalized epilepsy with febrile seizures plus, type 12

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

8 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
918042	NM_080552.3(SLC32A1):c.1403T>C (p.Leu468Pro)	SLC32A1	Pathogenic/Likely pathogenic	no assertion criteria provided
918043	NM_080552.3(SLC32A1):c.989T>C (p.Met330Thr)	SLC32A1	Pathogenic/Likely pathogenic	no assertion criteria provided
1329948	NM_080552.3(SLC32A1):c.787G>A (p.Val263Met)	SLC32A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3773699	NM_080552.3(SLC32A1):c.1232A>T (p.Gln411Leu)	SLC32A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4531753	NM_080552.3(SLC32A1):c.506G>A (p.Cys169Tyr)	SLC32A1	Uncertain significance	criteria provided, single submitter
4845397	NM_080552.3(SLC32A1):c.460_462del (p.Phe154del)	SLC32A1	Uncertain significance	criteria provided, single submitter
918044	NM_080552.3(SLC32A1):c.1391C>G (p.Thr464Arg)	SLC32A1	Uncertain significance	criteria provided, single submitter
918046	NM_080552.3(SLC32A1):c.1382G>A (p.Gly461Asp)	SLC32A1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
SLC32A1	Strong	Autosomal dominant	generalized epilepsy with febrile seizures plus, type 12	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC32A1	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SLC32A1	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
SLC32A1	HGNC:11018	ENSG00000101438	Q9H598	Vesicular inhibitory amino acid transporter	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC32A1	Vesicular inhibitory amino acid transporter	Antiporter that exchanges vesicular protons for cytosolic 4-aminobutanoate or to a lesser extend glycine, thus allowing their secretion from nerve terminals.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC32A1	Other/Unknown	no		AA_transpt_TM

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
nucleus accumbens	1
prefrontal cortex	1
putamen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC32A1	69	broad	marker	nucleus accumbens, putamen, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC32A1	3,331

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC32A1	Q9H598	78.69

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
GABA synthesis, release, reuptake and degradation	1	634.4×	0.002	SLC32A1
SLC-mediated transport of neurotransmitters	1	407.9×	0.002	SLC32A1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
beta-alanine transport	1	8426.0×	5e-04	SLC32A1
gamma-aminobutyric acid transport	1	8426.0×	5e-04	SLC32A1
gamma-aminobutyric acid import	1	2808.7×	7e-04	SLC32A1
neurotransmitter loading into synaptic vesicle	1	2808.7×	7e-04	SLC32A1
glycine transport	1	1404.3×	0.001	SLC32A1
neurotransmitter secretion	1	702.2×	0.002	SLC32A1
hippocampus development	1	230.8×	0.005	SLC32A1
monoatomic ion transport	1	156.0×	0.006	SLC32A1

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
SLC32A1	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	1	SLC32A1

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)
SLC32A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: SLC32A1