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Early onset or syndromic epilepsy v8.88 GLUL Achchuthan Shanmugasundram changed review comment from: PMID:38579670 (2024) reported nine unrelated individuals with severe global developmental delay, seizures, and white matter abnormalities but normal plasma and cerebrospinal fluid biochemistry. The epilepsy was characterized as generalized (4 individuals), combined general and focal (3), focal (1), or unknown (1). Most individuals had a developmental and epileptic encephalopathy, with one individual meeting diagnostic criteria for infantile epileptic spasms syndrome. 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 developmental delays 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.

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).; to: PMID:38579670 (2024) reported nine unrelated individuals with severe global developmental delay, seizures, and white matter abnormalities but normal plasma and cerebrospinal fluid biochemistry. The epilepsy was characterized as generalized (4 individuals), combined general and focal (3), focal (1), or unknown (1). Most individuals had a developmental and epileptic encephalopathy, with one individual meeting diagnostic criteria for infantile epileptic spasms syndrome. 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 developmental delays 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.

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).
Early onset or syndromic epilepsy v8.88 GLUL Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are >10 unrelated individuals reported with developmental and epileptic encephalopathy and monoallelic GLUL variants. Hence, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.
Early onset or syndromic epilepsy v8.88 GLUL Achchuthan Shanmugasundram Mode of inheritance for gene: GLUL was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v8.87 GLUL Achchuthan Shanmugasundram Phenotypes for gene: GLUL were changed from Glutamine deficiency, congenital, 610015; seizures 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
Early onset or syndromic epilepsy v8.86 GLUL Achchuthan Shanmugasundram Publications for gene: GLUL were set to 21353613; 16267323; 30158707
Early onset or syndromic epilepsy v8.85 GLUL Achchuthan Shanmugasundram Tag Q1_26_MOI tag was added to gene: GLUL.
Early onset or syndromic epilepsy v8.85 GLUL Achchuthan Shanmugasundram commented on gene: GLUL: PMID:38579670 (2024) reported nine unrelated individuals with severe global developmental delay, seizures, and white matter abnormalities but normal plasma and cerebrospinal fluid biochemistry. The epilepsy was characterized as generalized (4 individuals), combined general and focal (3), focal (1), or unknown (1). Most individuals had a developmental and epileptic encephalopathy, with one individual meeting diagnostic criteria for infantile epileptic spasms syndrome. 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 developmental delays 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.

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).
Early onset or syndromic epilepsy v8.85 GLUL Achchuthan Shanmugasundram reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: 38579670, 39985170, 41083803; 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; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.191 GLUL Rebecca Foulger Source Wessex and West Midlands GLH was added to GLUL.
Early onset or syndromic epilepsy v1.190 GLUL Rebecca Foulger Source NHS GMS was added to GLUL.
Early onset or syndromic epilepsy v1.189 GLUL Rebecca Foulger reviewed gene: GLUL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v1.188 GLUL Tracy Lester reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: ; Publications: 21353613, 16267323 ; Phenotypes: Glutamine deficiency, congenital, 610015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.954 GLUL Louise Daugherty Marked gene: GLUL as ready
Early onset or syndromic epilepsy v0.954 GLUL Louise Daugherty Gene: glul has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.954 GLUL Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Early onset or syndromic epilepsy v0.954 GLUL Louise Daugherty Publications for gene: GLUL were set to
Early onset or syndromic epilepsy v0.953 GLUL Louise Daugherty Classified gene: GLUL as Green List (high evidence)
Early onset or syndromic epilepsy v0.953 GLUL Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association.
Early onset or syndromic epilepsy v0.953 GLUL Louise Daugherty Gene: glul has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.914 GLUL Louise Daugherty Added comment: Comment on mode of inheritance: changed MOI from OMIM and publication PMID:16267323
Early onset or syndromic epilepsy v0.914 GLUL Louise Daugherty Mode of inheritance for gene: GLUL was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.913 GLUL Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.913 GLUL Louise Daugherty Phenotypes for gene: GLUL were changed from to Glutamine deficiency, congenital, 610015; seizures
Early onset or syndromic epilepsy GLUL Zornitza Stark reviewed gene: GLUL
Early onset or syndromic epilepsy GLUL Sarah Leigh Added gene to panel