GADL1

Chr 3

GAD like acidic amino acid decarboxylase 1

Also known as: ADC, CSADC, HuADC, HuCSADC

NCBI Gene: 339896 ENSG00000144644 UniProt: Q6ZQY3 OMIM: 615601

GADL1 encodes a carboxy-lyase that catalyzes the decarboxylation of L-aspartate and sulfur-containing amino acids to produce beta-alanine, hypotaurine, and taurine. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and developmental regression. The gene is not loss-of-function intolerant, consistent with the recessive inheritance pattern observed in affected patients.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable carboxy-lyase activity. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.43

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score -0.29

OE 1.06 (0.79–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.72Z-score

OE missense 1.12 (1.02–1.24)

306 obs / 272.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.06 (0.79–1.43)

0≤0.351.4

Missense OE?1.12 (1.02–1.24)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 31 / 29.3Missense obs/exp: 306 / 272.4Syn Z: -1.08

Background carrier burden — how many people carry a rare variant somewhere in GADL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 63

790 rare PASS variants

Rare truncating (LoF)

1 in 310

169 rare PASS variants

Rare synonymous (reference)

1 in 180

278 rare PASS variants

Rare missense and truncating variants are carried at similar rates in GADL1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 91	1 in 880
South Asian	~43k	1 in 78	1 in 780
Remaining (unassigned)	~30k	1 in 63	1 in 300
European (Finnish)	~27k	1 in 220	1 in 3,800
Admixed American	~22k	1 in 79	1 in 1,100
African / African American	~21k	1 in 61	1 in 560
East Asian	~20k	1 in 61	1 in 510
Ashkenazi Jewish	~13k	1 in 490	none seen
Middle Eastern	~2,883	1 in 87	1 in 360

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 15 coding exons well covered in gnomAD exomes; exons 4, 5, 6, 9, 13 marginal. Genomes: all 15.? see exons ↓