GAD2

Chr 10

glutamate decarboxylase 2

Also known as: GAD65

The protein catalyzes the production of GABA (gamma-aminobutyric acid) from glutamic acid, serving as a key enzyme in GABAergic neurotransmission. Mutations cause early-onset epileptic encephalopathy, typically presenting in infancy with seizures and developmental delays. The gene shows high constraint against loss-of-function variants (LOEUF 0.372), and inheritance follows an autosomal recessive pattern.

Summary from RefSeq, UniProt
Research Assistant →
3
Active trials
68
Pubs (1 yr)
11
P/LP submissions
0%
P/LP missense
0.37
LOEUF
Mechanism
Clinical SummaryGAD2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 80 VUS of 105 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.37LOEUF
pLI 0.751
Z-score 4.42
OE 0.20 (0.110.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.53Z-score
OE missense 0.77 (0.690.85)
258 obs / 337.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.110.37)
00.351.4
Missense OE0.77 (0.690.85)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 7 / 35.4Missense obs/exp: 258 / 337.0Syn Z: 0.03

ClinVar Variant Classifications

105 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS80
Likely Benign4
Benign7
10
Pathogenic
1
Likely Pathogenic
80
VUS
4
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
78
2
0
80
Likely Benign
0
2
1
1
4
Benign
0
2
2
3
7
Total082164102

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GAD2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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