Aminoacidopathy

Gene: GLS

Green List (high evidence)

DEFINITIVE for bi-allelic disease by ClinGen. LIMITED for mono-allelic.

Created: 7 Aug 2024, 9:25 p.m. | Last Modified: 7 Aug 2024, 9:25 p.m.

Panel Version: 1.128

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Glutaminase deficiency MONDO:0600001; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685

I don't know

Classified as Moderate by ClinGen Aminoacidopathy GCEP on 26/07/2024 - https://search.clinicalgenome.org/CCID:004966

Two unrelated probands have been reported with an increased glutamate production level. Two missense variants have been reported (Ser482Cys and His461Leu - both absent from gnomAD v4.1). A zebrafish model partially recapitulated the disease.

Created: 5 Aug 2024, 12:14 a.m. | Last Modified: 5 Aug 2024, 12:14 a.m.

Panel Version: 1.128

Classified Definitive by ClinGen Aminoacidopathy GCEP on 09/07/2021 - https://search.clinicalgenome.org/CCID:004965

6 probands have been reported with glutaminase deficiency. Nonsense, framshift and missense variants have been reported. 5’UTR repeat expansion (680-1500 repeats; normal range 8-16 repeats) has also been reported.
Mouse model was also conducted that recapitulates the human phenotype (PMID: 16641247).
Sources: ClinGen

Created: 5 Jun 2024, 7:49 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685

Publications

• 30239721, 37151363

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments