GLUL

Chr 1ADAR

glutamate-ammonia ligase

Also known as: DEE116, GLNS, GS, PIG43, PIG59

The protein catalyzes the ATP-dependent synthesis of glutamine from glutamate and ammonia, serving critical functions in ammonia detoxification, acid-base homeostasis, and providing glutamine for amino acid, pyrimidine, and purine biosynthesis. Loss-of-function mutations cause congenital glutamine deficiency and developmental and epileptic encephalopathy 116 through both autosomal dominant and autosomal recessive inheritance patterns. The high pLI score (0.996) indicates this gene is highly intolerant to loss-of-function variants, consistent with its essential metabolic role.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAD/ARLOEUF 0.182 OMIM phenotypes
Clinical SummaryGLUL
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Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ADModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.18LOEUF
pLI 0.996
Z-score 3.72
OE 0.00 (0.000.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.60Z-score
OE missense 0.70 (0.610.80)
156 obs / 223.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.18)
00.351.4
Missense OE0.70 (0.610.80)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 0 / 16.1Missense obs/exp: 156 / 223.5Syn Z: -1.39
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGLUL-related congenital systemic glutamine deficiencyOTHERAR

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

DN
0.3793th %ile
GOF
0.3590th %ile
LOF
0.66top 25%

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GLUL · 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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