GLUL

Chr 1

glutamate-ammonia ligase

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

NCBI Gene: 2752 ENSG00000135821 UniProt: P15104

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.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene belongs to the glutamine synthetase family. It catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. This protein plays a role in ammonia and glutamate detoxification, acid-base homeostasis, cell signaling, and cell proliferation. Glutamine is an abundant amino acid, and is important to the biosynthesis of several amino acids, pyrimidines, and purines. Mutations in this gene are associated with congenital glutamine deficiency, and overexpression of this gene was observed in some primary liver cancer samples. There are six pseudogenes of this gene found on chromosomes 2, 5, 9, 11, and 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtGlutamine deficiency, congenital

UniProtDevelopmental and epileptic encephalopathy 116

Clinical highlights

Gene-disease validity (ClinGen)

congenital brain dysgenesis due to glutamine synthetase deficiency · ARModerateconsider for supplementary testing2 gene-disease associations curated in total

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.18

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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