GLUL

Chr 1q25.3

glutamate-ammonia ligase

MANE:: ENST00000331872.11

OMIM: 138290 ↗NCBI: 2752 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

GLUL · P15104

v62025-08-01

Predicted Aligned Error matrix for GLUL — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

97.5/ 100

Very high

373 residues

Confidence breakdown

Very high(≥ 90)97%
Confident(70–90)2%
Low(50–70)1%
Very low(< 50)0%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders
BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder

Disease associations (Open Targets)

congenital brain dysgenesis due to glutamine synthetase deficiency
0.79
developmental and epileptic encephalopathy 116
0.66
neurodegenerative disease
0.52
progressive myoclonic epilepsy with dystonia
0.49
malignant migrating partial seizures of infancy
0.49
hereditary disease
0.19
genetic developmental and epileptic encephalopathy
0.18
hepatocellular carcinoma
0.11
neoplasm
0.10
gastrointestinal disease
0.09

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Glutamine synthetase

Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (PubMed:16267323, PubMed:30158707, PubMed:36289327). Its role depends on tissue localization: in the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia (By similarity). Plays a key role in ammonium detoxification during erythropoiesis: the glutamine synthetase activity is required to remove ammonium generated by porphobilinogen deaminase (HMBS) during heme biosynthesis to prevent ammonium accumulation and oxidative stress (By similarity). Essential for proliferation of fetal skin fibroblasts (PubMed:18662667). Independently of its glutamine synthetase activity, required for endothelial cell migration during vascular development: acts by regulating membrane localization and activation of the GTPase RHOJ, possibly by promoting RHOJ palmitoylation (PubMed:30158707). May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ (PubMed:30158707). Plays a role in ribosomal 40S subunit biogenesis (PubMed:26711351). Through the interaction with BEST2, inhibits BEST2 channel activity by affecting the gating at the aperture in the absence of intracellular L-glutamate, but sensitizes BEST2 to intracellular L-glutamate, which promotes the opening of BEST2 and thus relieves its inhibitory effect on BEST2 (PubMed:36289327)