GAD1

Chr 2

glutamate decarboxylase 1

Also known as: CPSQ1, DEE89, GAD, GAD-67, SCP

NCBI Gene: 2571 ENSG00000128683 UniProt: Q99259

This enzyme catalyzes the synthesis of gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter, using pyridoxal 5'-phosphate as a cofactor. Autosomal recessive mutations cause developmental and epileptic encephalopathy 89, characterized by pyridoxine-dependent seizures due to deficient GABA production. Loss of enzyme function reduces inhibitory neurotransmission, leading to seizure susceptibility that responds to pyridoxine supplementation.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes one of several forms of glutamic acid decarboxylase, identified as a major autoantigen in insulin-dependent diabetes. The enzyme encoded is responsible for catalyzing the production of gamma-aminobutyric acid from L-glutamic acid. A pathogenic role for this enzyme has been identified in the human pancreas since it has been identified as an autoantigen and an autoreactive T cell target in insulin-dependent diabetes. This gene may also play a role in the stiff man syndrome. Deficiency in this enzyme has been shown to lead to pyridoxine dependency with seizures. Alternative splicing of this gene results in two products, the predominant 67-kD form and a less-frequent 25-kD form. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 89

Clinical highlights

Gene-disease validity (ClinGen)

obsolete early infantile epileptic encephalopathy · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

113

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.47

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)