Familial sleep-related hypermotor epilepsy: genes and variants
Familial sleep-related hypermotor epilepsy is linked to 2 analyzed proteins (CHRNA4 and GABRG2). 5 DNA variants are known to cause it; 386 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Familial sleep-related hypermotor epilepsy
CHRNA4: Neuronal acetylcholine receptor subunit alpha-4
It contributes to neuronal nicotinic acetylcholine responses that regulate excitability and neurotransmitter release. Dominant gain-of-function variants classically cause sleep-related hypermotor epilepsy, formerly termed autosomal dominant nocturnal frontal-lobe epilepsy.
3 disease-causing and 386 uncertain variants in CHRNA4 are linked to Familial sleep-related hypermotor epilepsy.
GABRG2: Gamma-aminobutyric acid receptor subunit gamma-2
The gene product supplies the gamma-2 subunit of synaptic GABA-A receptors, which are pentameric chloride channels activated by the inhibitory neurotransmitter GABA. The subunit helps receptor assembly and localization at neuronal membranes, and GABRG2 variants are associated with several epilepsy syndromes.
2 disease-causing and 0 uncertain variants in GABRG2 are linked to Familial sleep-related hypermotor epilepsy.
Known disease-causing variants in Familial sleep-related hypermotor epilepsy
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CHRNA4 I275F | 275 | Transmembrane | Disease-causing (★★) |
| CHRNA4 S280F | 280 | Transmembrane | Disease-causing (★★) |
| CHRNA4 S284L | 284 | Transmembrane | Disease-causing (★★) |
| GABRG2 T317N | 317 | Transmembrane | Disease-causing |
| GABRG2 T316N | 316 | Transmembrane | Disease-causing |
Same protein, different disease
- Febrile seizures, familial, 3a is also caused by GABRG2 variants; they fall mostly in different places as the Familial sleep-related hypermotor epilepsy variants (31 disease-causing).
- EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2 is also caused by GABRG2 variants; they fall mostly in different places as the Familial sleep-related hypermotor epilepsy variants (28 disease-causing).
Diseases related to Familial sleep-related hypermotor epilepsy
- Generalized epilepsy with febrile seizures plus, also linked to GABRG2
- EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2, also linked to GABRG2
- Febrile seizures, familial, 3a, also linked to GABRG2
- Epilepsy, also linked to GABRG2
- Self-limited epilepsy with centrotemporal spikes, also linked to GABRG2
- Genetic developmental and epileptic encephalopathy, also linked to GABRG2
- Lennox-Gastaut syndrome, also linked to GABRG2
- Autosomal dominant nocturnal frontal lobe epilepsy, also linked to CHRNA4
Frequently asked questions
Which genes are linked to Familial sleep-related hypermotor epilepsy?
In CATVariant, Familial sleep-related hypermotor epilepsy is linked to 2 analyzed proteins: CHRNA4 (Neuronal acetylcholine receptor subunit alpha-4) and GABRG2 (Gamma-aminobutyric acid receptor subunit gamma-2).
How many genetic variants are linked to Familial sleep-related hypermotor epilepsy?
459 variants: 5 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 386 are of uncertain significance or have conflicting reports.
Which uncertain variants in Familial sleep-related hypermotor epilepsy look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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