GLS2
protein-codingglutaminase 2, the group of Ankyrin repeat domain containing
Gene summary
The protein encoded by this gene is a mitochondrial phosphate-activated glutaminase that catalyzes the hydrolysis of glutamine to stoichiometric amounts of glutamate and ammonia. Originally thought to be liver-specific, this protein has been found in other tissues as well. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GLS2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_013267.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 66 | 1 | 67 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 72 | 2 | 1 | 75 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_037399.2 | 18 | MANE Select | |
| Ensembl | ENSP00000310447.4 | 18 | MANE Select | |
| RefSeq | NP_001267725.1 | 10 | Standard | |
| RefSeq | NP_001267726.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- cellular amino acid metabolic process
- glutamate biosynthetic process
- glutamine catabolic process
- cellular amino acid biosynthetic process
- glutamate secretion
Molecular Function
- glutaminase activity
- protein binding
Cellular Component
- mitochondrion
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000311966
- Coding exons
- 18
- Length
- 17463
- Individuals with no LoFs
- 125670
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 78
- Defined
- 125748
- p
- 0.000310
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.35 | 221 | 344 | 0.643 | 0.0000185 | 3940 |
| Missense (PolyPhen) | 58 | 103.41 | 0.56086 | 1159 | ||
| Synonymous | 0.0718 | 126 | 127 | 0.992 | 0.00000650 | 1158 |
| Loss of Function | 2.38 | 22 | 37.8 | 0.582 | 0.00000230 | 395 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00032 | 0.00032 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00037 | 0.00033 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation. {ECO:0000269|PubMed:20378837}.;
Recessive Scores
- pRec
- 0.281
Intolerance Scores
- LoFtool
- 0.778
- RVIS EVS
- -0.54
- RVIS percentile EVS
- 20.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.740
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |