GLUL glutamate-ammonia ligase [Homo sapiens (human)] - Gene

Summary

Official Symbol: GLULprovided by HGNC
Official Full Name: glutamate-ammonia ligaseprovided by HGNC
Primary source: HGNC:HGNC:4341
See related: Ensembl:ENSG00000135821 MIM:138290; AllianceGenome:HGNC:4341
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GS; GLNS; PIG43; PIG59; DEE116
Summary: 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]
Expression: Ubiquitous expression in fat (RPKM 227.2), brain (RPKM 128.5) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q25.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (182378098..182391790, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (181737671..181751363, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (182347233..182360925, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.
Title: Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.
Leat-associated seizures the possible role of EAAT2, pyruvate carboxylase and glutamine synthetase.
Title: Leat-associated seizures the possible role of EAAT2, pyruvate carboxylase and glutamine synthetase.
Glutamine synthetase and hepatocellular carcinoma.
Title: Glutamine synthetase and hepatocellular carcinoma.
PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma.
Title: PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma.
Single-cell and spatial analyses reveal the association between gene expression of glutamine synthetase with the immunosuppressive phenotype of APOE+CTSZ+TAM in cancers.
Title: Single-cell and spatial analyses reveal the association between gene expression of glutamine synthetase with the immunosuppressive phenotype of APOE+CTSZ+TAM in cancers.
Multiple oxidative post-translational modifications of human glutamine synthetase mediate peroxynitrite-dependent enzyme inactivation and aggregation.
Title: Multiple oxidative post-translational modifications of human glutamine synthetase mediate peroxynitrite-dependent enzyme inactivation and aggregation.
Glutamine synthetase limits beta-catenin-mutated liver cancer growth by maintaining nitrogen homeostasis and suppressing mTORC1.
Title: Glutamine synthetase limits β-catenin-mutated liver cancer growth by maintaining nitrogen homeostasis and suppressing mTORC1.
Glutamine synthetase regulates the immune microenvironment and cancer development through the inflammatory pathway.
Title: Glutamine synthetase regulates the immune microenvironment and cancer development through the inflammatory pathway.
Crystal structure of N-terminal degron-truncated human glutamine synthetase.
Title: Crystal structure of N-terminal degron-truncated human glutamine synthetase.
Downregulation of Glutamine Synthetase, not glutaminolysis, is responsible for glutamine addiction in Notch1-driven acute lymphoblastic leukemia.
Title: Downregulation of Glutamine Synthetase, not glutaminolysis, is responsible for glutamine addiction in Notch1-driven acute lymphoblastic leukemia.

Submit: New GeneRIF Correction See all GeneRIFs (67)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Congenital brain dysgenesis due to glutamine synthetase deficiency MedGen: C1864910 OMIM: 610015 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Association between a genetic variant related to glutamic acid metabolism and coronary heart disease in individuals with type 2 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 significantly reduces the activity of glutamine synthase (GS) in human cultured astroglial cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70547 (e-PCR)
- UniSTS:90670

D1S2009E (e-PCR)
- UniSTS:151347

D1S2414 (e-PCR)
- UniSTS:51019

D1S290E (e-PCR)
- UniSTS:147539

D1S1423 (e-PCR)
- UniSTS:149619

D1S2075E (e-PCR)
- UniSTS:151695

D1S290E (e-PCR)
- UniSTS:61583

SGC30288 (e-PCR)
- UniSTS:82622

Cda0jg12 (e-PCR)
- UniSTS:90082

D1S290E (e-PCR)
- UniSTS:78318

SHGC-75989 (e-PCR)
- UniSTS:38644

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables glutamine synthetase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glutamine synthetase activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-cysteine S-palmitoyltransferase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to starvation	IEA Inferred from Electronic Annotation more info
involved_in glutamate catabolic process	TAS Traceable Author Statement more info	PubMed
involved_in glutamine biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glutamine biosynthetic process	TAS Traceable Author Statement more info	PubMed
involved_in protein palmitoylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of protein localization to nucleolus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of sprouting angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in response to glucose	IEA Inferred from Electronic Annotation more info
involved_in ribosome biogenesis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cell body	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in glial cell projection	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in nucleus	HDA more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: glutamine synthetase

Names: cell proliferation-inducing protein 59; glutamate decarboxylase; glutamine synthase; palmitoyltransferase GLUL; proliferation-inducing protein 43

NP_001028216.1

EC 2.3.1.225

EC 6.3.1.2

NP_001028228.1

EC 2.3.1.225

EC 6.3.1.2

NP_002056.2

EC 2.3.1.225

EC 6.3.1.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.