GAD1

Chr 2AR

glutamate decarboxylase 1

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 0.471 OMIM phenotype
Clinical SummaryGAD1
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Gene-Disease Validity (ClinGen)
obsolete early infantile epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.046
Z-score 3.89
OE 0.27 (0.160.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.32Z-score
OE missense 0.64 (0.580.72)
217 obs / 336.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.27 (0.160.47)
00.351.4
Missense OE0.64 (0.580.72)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 9 / 33.1Missense obs/exp: 217 / 336.5Syn Z: 0.29
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedGAD1-related cerebral palsy spastic quadriplegicOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6937th %ile
GOF
0.6443th %ile
LOF
0.3744th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GAD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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