Human Disease Model Report: myoclonic-atonic epilepsy

General Information

Name

myoclonic-atonic epilepsy

FlyBase ID

FBhh0001504

Disease Ontology Term

myoclonic-atonic epilepsy

Parent Disease

OMIM

MYOCLONIC-ATONIC EPILEPSY; MAE

Overview

This report describes myoclonic-atonic epilepsy, a seizure disorder that exhibits autosomal dominant inheritance. The human gene implicated is SLC6A1, which encodes solute carrier family 6 member 1, a GABA transporter. There is one high-scoring fly ortholog, Dmel\Gat, for which amorphic function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

UAS constructs of the human Hsap\SLC6A1 gene, including wild-type SLC6A1 and variants implicated in disease, have been introduced into flies. See the 'Disease-Implicated Variants' table below.

Dmel\Gat is expressed exclusively in astrocytes. When driven in astrocytes, wild-type Hsap\SLC6A1 colocalizes with cell membrane markers, while the human A288V mutant colocalizes only with ER markers. Astrocyte-specific expression of the human A288V mutant displays a heat-induced seizure phenotype; subsequently the same phenotype has been observed for G443V and G443D variants. Pharmaceutical interventions have been assessed using this disease model.

[updated Jun. 2025 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: myoclonic-atonic epilepsy

OMIM report

[MYOCLONIC-ATONIC EPILEPSY; MAE](https://omim.org/entry/616421)

Human gene(s) implicated

[SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, GABA), MEMBER 1; SLC6A1](https://omim.org/entry/137165)

Symptoms and phenotype

Myoclonic-atonic epilepsy (MAE) is an autosomal dominant disorder characterized by onset of absence and myoclonic seizures in early childhood. Patients have delayed development before the onset of seizures and show varying degrees of impaired intellectual development following seizure onset (summary by Carvill et al., 2015, pubmed:25865495). [from MIM:616421; 2022.11.08]

(OMIM, 2013-)

Genetics

Myoclonic-atonic epilepsy (MAE) is caused by heterozygous mutation in the SLC6A1 gene on chromosome 3p25. [from MIM:616421; 2022.11.08]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

The SLC6A1 gene encodes a gamma-aminobutyric acid (GABA) transporter, which removes GABA from the synaptic cleft (Hirunsatit et al., 2009, pubmed:19077666). [from MIM:137165; 2023.03.15]

(OMIM, 2013-)

External links

Gene2Function (human gene): SLC6A1
Gene Cards: SLC6A1
MedlinePlus (gene): SLC6A1
MARRVEL (human gene): SLC6A1
NCBI MedGen: Myoclonic-atonic epilepsy (MAE)
NCBI (Entrez) gene: SLC6A1; solute carrier family 6 member 1

Disease synonyms

MAE

Related Diseases

Related human health report(s)

epilepsy

Ortholog Information

Human gene(s) in FlyBase

Hsap\SLC6A1

Human gene (HGNC)

Symbol / Name

SLC6A1; solute carrier family 6 member 1

D. melanogaster ortholog (based on DIOPT)

Dmel\Gat

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one (many human to 1 Drosophila); SLC6A1 has one high-scoring Drosophila ortholog, Gat.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Gat

Gene Snapshot

GABA transporter (Gat) encodes a protein belonging to the SLC family that is expressed primarily in astrocytes, where it is thought to be required for uptake of GABA and other small molecules. It likely plays an important role in setting the excitatory/inhibitory balance of the CNS. [Date last reviewed: 2019-03-07]

Molecular function (GO)