GLS2

glutaminase 2, the group of Ankyrin repeat domain containing

Basic information

Region (hg38): 12:56470944-56488414

Links

ENSG00000135423 ∙ NCBI:27165 ∙ OMIM:606365 ∙ HGNC:29570 ∙ Uniprot:Q9UI32 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GLS2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLS2 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				1		1
missense			18	1	1	20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	18	2	1

Variants in GLS2

This is a list of pathogenic ClinVar variants found in the GLS2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-56471555-G-A		not specified	Uncertain significance (Jun 22, 2021)
12-56471611-T-A		not specified	Uncertain significance (Mar 19, 2024)
12-56471836-C-T		not specified	Uncertain significance (May 31, 2023)
12-56473229-C-T		not specified	Uncertain significance (Nov 27, 2023)
12-56473266-G-A		not specified	Uncertain significance (Jun 02, 2023)
12-56473561-C-T		not specified	Uncertain significance (Nov 08, 2022)
12-56474590-A-C		not specified	Uncertain significance (May 16, 2024)
12-56474667-G-A			Likely benign (May 01, 2022)
12-56474684-C-T		not specified	Uncertain significance (Jun 11, 2021)
12-56474882-C-T			Benign (Mar 29, 2018)
12-56475067-C-T		not specified	Uncertain significance (Oct 18, 2021)
12-56475081-C-T		not specified	Uncertain significance (Jan 24, 2024)
12-56475621-T-C			Likely benign (Apr 10, 2018)
12-56475643-T-C		not specified	Uncertain significance (Jun 29, 2023)
12-56475655-C-T		not specified	Uncertain significance (May 25, 2022)
12-56477954-T-G		not specified	Uncertain significance (Sep 12, 2023)
12-56477955-G-C		not specified	Uncertain significance (Sep 12, 2023)
12-56478013-A-C		not specified	Uncertain significance (Jan 30, 2024)
12-56478028-A-G		not specified	Uncertain significance (May 24, 2023)
12-56479090-G-A		not specified	Uncertain significance (Feb 26, 2024)
12-56479795-C-T		not specified	Uncertain significance (Dec 03, 2021)
12-56480313-C-T		not specified	Likely benign (Sep 20, 2023)
12-56480370-C-T		not specified	Uncertain significance (Dec 17, 2021)
12-56488102-G-A		not specified	Uncertain significance (Nov 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GLS2	protein_coding	protein_coding	ENST00000311966	18	17463

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.32e-10	0.985	125670	0	78	125748	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.35	221	344	0.643	0.0000185	3940
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000749	0.000749
Ashkenazi Jewish	0.00	0.00
East Asian	0.000652	0.000653
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000366	0.000325
Middle Eastern	0.000652	0.000653
South Asian	0.000328	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• 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);Warburg Effect;Argininemia;2-Hydroxyglutric Aciduria (D And L Form);Ammonia Recycling;Citrullinemia Type I;Carbamoyl Phosphate Synthetase Deficiency;Argininosuccinic Aciduria;Urea Cycle;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;Homocarnosinosis;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Hyperinsulinism-Hyperammonemia Syndrome;Succinic semialdehyde dehydrogenase deficiency;Ornithine Transcarbamylase Deficiency (OTC Deficiency);4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency;Glutamate Metabolism;TP53 Regulates Metabolic Genes;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)

Recessive Scores

• pRec: 0.281

Intolerance Scores

• loftool: 0.778
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

• pHI: 0.677
• hipred: Y
• hipred_score: 0.563
• ghis: 0.561

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.740

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gls2

Gene ontology

• Biological process: cellular amino acid metabolic process;glutamate biosynthetic process;glutamine catabolic process;cellular amino acid biosynthetic process;glutamate secretion;regulation of apoptotic process;reactive oxygen species metabolic process
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: glutaminase activity;protein binding