GLS
glutaminase, the group of Ankyrin repeat domain containing
Basic information
Region (hg38): 2:190880821-190965552
Links
Phenotypes
GenCC
Source:
- developmental and epileptic encephalopathy, 71 (Limited), mode of inheritance: AR
- global developmental delay, progressive ataxia, and elevated glutamine (Strong), mode of inheritance: AR
- infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development (Limited), mode of inheritance: Unknown
- glutaminase deficiency (Moderate), mode of inheritance: AR
- infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development (Moderate), mode of inheritance: AD
- glutaminase deficiency (Definitive), mode of inheritance: AR
- infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development; Epileptic encephalopathy, early infantile, 71; Global developmental delay, progressive ataxia, and elevated glutamine | AD/AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Biochemical; Dermatologic; Neurologic; Ophthalmologic | 30239721; 30575854; 30970188 |
| Global developmental delay, progressive ataxia, and elevated glutamine is caused by triplet repeat expansion upstream of the GLS gene |
ClinVar
This is a list of variants' phenotypes submitted to
- Developmental and epileptic encephalopathy, 71 (4 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLS gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | |||||
| missense | 36 | 46 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 3 | 1 | 4 | |||
| non coding | 10 | |||||
| Total | 4 | 5 | 37 | 17 | 5 |
Variants in GLS
This is a list of pathogenic ClinVar variants found in the GLS region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GLS | protein_coding | protein_coding | ENST00000320717 | 18 | 84726 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.962 | 0.0385 | 125721 | 0 | 14 | 125735 | 0.0000557 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.73 | 133 | 321 | 0.414 | 0.0000151 | 4330 |
| Missense in Polyphen | 16 | 86.415 | 0.18515 | 1095 | ||
| Synonymous | 0.919 | 102 | 115 | 0.891 | 0.00000557 | 1292 |
| Loss of Function | 4.69 | 6 | 36.6 | 0.164 | 0.00000209 | 445 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000926 | 0.0000924 |
| European (Non-Finnish) | 0.0000891 | 0.0000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000654 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate in the brain. Isoform 2 lacks catalytic activity.;
- Pathway
- Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);D-Glutamine and D-glutamate metabolism - Homo sapiens (human);Proximal tubule bicarbonate reclamation - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Arginine biosynthesis - Homo sapiens (human);Amino Acid metabolism;Gene expression (Transcription);Generic Transcription Pathway;Glutamate Glutamine metabolism;Metabolism of amino acids and derivatives;RNA Polymerase II Transcription;Metabolism;glutamine degradation/glutamate biosynthesis;Neuronal System;TP53 Regulates Metabolic Genes;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Glutamate Neurotransmitter Release Cycle;Neurotransmitter release cycle;Transcriptional Regulation by TP53;Transmission across Chemical Synapses;Amino acid synthesis and interconversion (transamination)
(Consensus)
Intolerance Scores
- loftool
- 0.369
- rvis_EVS
- 0.15
- rvis_percentile_EVS
- 64.32
Haploinsufficiency Scores
- pHI
- 0.134
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.516
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.950
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gls
- Phenotype
- normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Gene ontology
- Biological process
- suckling behavior;regulation of respiratory gaseous exchange by neurological system process;glutamate biosynthetic process;glutamine catabolic process;chemical synaptic transmission;cellular amino acid biosynthetic process;glutamate secretion;protein homotetramerization
- Cellular component
- mitochondrion;mitochondrial matrix;cytosol
- Molecular function
- glutaminase activity;protein binding