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Intellectual disability

Gene: GLUL

Green List (high evidence)
GLUL (glutamate-ammonia ligase)
EnsemblGeneIds (GRCh38): ENSG00000135821
EnsemblGeneIds (GRCh37): ENSG00000135821
OMIM: 138290, Gene2Phenotype
GLUL is in 7 panels

5 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on mode of inheritance: There are >10 unrelated individuals reported with developmental and epileptic encephalopathy, including global developmental delay and monoallelic GLUL variants. Hence, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.
Created: 7 Jan 2026, 11:51 a.m. | Last Modified: 7 Jan 2026, 11:51 a.m.
Panel Version: 9.227
PMID:38579670 (2024) reported nine unrelated individuals with severe global developmental delay, seizures, and white matter abnormalities but normal plasma and cerebrospinal fluid biochemistry. They were identified with heterozygous de novo variants in GLUL gene via whole-exome sequencing. Seven out of nine were start-loss variants and two out of nine disrupted 5' UTR splicing resulting in splice exclusion of the initiation codon.

PMID:39985170 (2025) reported a male proband with a phenotype of refractory focal and generalized seizures and global developmental delay and identified with a heterozygous de novo start-codon-disrupting variant in GLUL (c.-13-2A>G).

PMID:41083803 (2025) reported three additional unrelated patients with heterozygous de novo GLUL variants identified via trio whole-exome sequencing and with developmental and epileptic encephalopathy. All three patients had global developmental delay.

Both monoallelic and biallelic variants in this gene have been associated with relevant phenotypes in OMIM (MIMs #610015 & #620806, last accessed 07 January 2026) and ClinGen (both AR and AD diseases with 'moderate' rating). Only biallelic variants are currently associated with phenotype in Gene2Phenotype ('definitive' rating on DD panel).
Created: 7 Jan 2026, 11:48 a.m. | Last Modified: 7 Jan 2026, 11:48 a.m.
Panel Version: 9.224

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Glutamine deficiency, congenital, OMIM:610015; Developmental and epileptic encephalopathy 116, OMIM:620806; congenital brain dysgenesis due to glutamine synthetase deficiency, MONDO:0012393; developmental and epileptic encephalopathy 116, MONDO:0970945

Publications

Created: 7 Jan 2026, 11:48 a.m.
Last Modified: 7 Jan 2026, 11:48 a.m.
Panel version: 9.224

Caroline Wright (Sanger)

I don't know

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
CONGENITAL SYSTEMIC GLUTAMINE DEFICIENCY (CSGD)

Publications

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf . Main mutation mechanism : Uncertain
Created: 27 Jul 2017, 6:19 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; GEL_ID_green_20160217; neuro_20160418_strict; Uncertain. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 12:33 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 2 Aug 2017, 6:33 p.m.

Panel version: 1.354

Lu Raymond (university of cambridge )

I don't know

Created: 23 Feb 2016, 10:06 a.m.

Panel version: 0.306

Richard Scott (Genomics England Curator)

Comment on list classification: Confirmed DD gene
Created: 7 Feb 2016, 8:50 p.m.
Created: 7 Feb 2016, 8:50 p.m.

Panel version: 0.139

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Victorian Clinical Genetics Services
  • Expert Review Green
Phenotypes
  • Glutamine deficiency, congenital, OMIM:610015
  • Developmental and epileptic encephalopathy 116, OMIM:620806
  • congenital brain dysgenesis due to glutamine synthetase deficiency, MONDO:0012393
  • developmental and epileptic encephalopathy 116, MONDO:0970945
Tags
Q1_26_MOI
OMIM
138290
Clinvar variants
Variants in GLUL
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

7 Jan 2026, Gel status: 3

Set mode of inheritance

Achchuthan Shanmugasundram (Genomics England Curator)

Mode of inheritance for gene: GLUL was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

7 Jan 2026, Gel status: 3

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GLUL were changed from CONGENITAL SYSTEMIC GLUTAMINE DEFICIENCY (CSGD) to Glutamine deficiency, congenital, OMIM:610015; Developmental and epileptic encephalopathy 116, OMIM:620806; congenital brain dysgenesis due to glutamine synthetase deficiency, MONDO:0012393; developmental and epileptic encephalopathy 116, MONDO:0970945

7 Jan 2026, Gel status: 3

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: GLUL were set to 21353613; 16267323

7 Jan 2026, Gel status: 3

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q1_26_MOI tag was added to gene: GLUL.

28 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to GLUL.

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

7 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

7 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

GLUL was created by ellenmcdonagh

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

GLUL was added to Intellectual disabilitypanel. Sources: Expert Review Amber