Seroatlas · Human Serome Atlas

GLS

Glutaminase kidney isoform, mitochondrial

Also known as: GAC, GAM, GLS1, GLSK_HUMAN, KGA, KIAA0838

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: O94925
Gene: GLS
Ensembl: ENSG00000115419
Chromosome: 2
Canonical length: 669 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location: Mitochondria
Quaternary structure: Homotetramer

OverviewNCBI Gene

This gene encodes the K-type mitochondrial glutaminase. The encoded protein is an phosphate-activated amidohydrolase that catalyzes the hydrolysis of glutamine to glutamate and ammonia. This protein is primarily expressed in the brain and kidney plays an essential role in generating energy for metabolism, synthesizing the brain neurotransmitter glutamate and maintaining acid-base balance in the kidney. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

Canonical amino-acid sequenceUniProt

669 residues, UniProt reviewed canonical sequence.

>O94925|GLS
     1  MMRLRGSGML RDLLLRSPAG VSATLRRAQP LVTLCRRPRG GGRPAAGPAA AARLHPWWGG
    61  GGWPAEPLAR GLSSSPSEIL QELGKGSTHP QPGVSPPAAP AAPGPKDGPG ETDAFGNSEG
   121  KELVASGENK IKQGLLPSLE DLLFYTIAEG QEKIPVHKFI TALKSTGLRT SDPRLKECMD
   181  MLRLTLQTTS DGVMLDKDLF KKCVQSNIVL LTQAFRRKFV IPDFMSFTSH IDELYESAKK
   241  QSGGKVADYI PQLAKFSPDL WGVSVCTVDG QRHSTGDTKV PFCLQSCVKP LKYAIAVNDL
   301  GTEYVHRYVG KEPSGLRFNK LFLNEDDKPH NPMVNAGAIV VTSLIKQGVN NAEKFDYVMQ
   361  FLNKMAGNEY VGFSNATFQS ERESGDRNFA IGYYLKEKKC FPEGTDMVGI LDFYFQLCSI
   421  EVTCESASVM AATLANGGFC PITGERVLSP EAVRNTLSLM HSCGMYDFSG QFAFHVGLPA
   481  KSGVAGGILL VVPNVMGMMC WSPPLDKMGN SVKGIHFCHD LVSLCNFHNY DNLRHFAKKL
   541  DPRREGGDQR VKSVINLLFA AYTGDVSALR RFALSAMDME QRDYDSRTAL HVAAAEGHVE
   601  VVKFLLEACK VNPFPKDRWN NTPMDEALHF GHHDVFKILQ EYQVQYTPQG DSDNGKENQT
   661  VHKNLDGLL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GLS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.35
Highest tissue expression: 144 nTPM

Expression across tissuesHPA

Tissue

kidney: 144 nTPM
cerebral cortex: 79 nTPM
blood vessel: 78 nTPM
cerebellum: 72 nTPM
adrenal gland: 66 nTPM
small intestine: 62 nTPM

Single-cell type

renal connecting tubule cells: 847 nCPM
podocytes: 821 nCPM
renal collecting duct principal cells: 812 nCPM
ocular epithelial cells: 737 nCPM
distal convoluted tubule cells: 652 nCPM
alveolar cells type 1: 542 nCPM

Immune cell

basophil: 6.2 nTPM
MAIT T-cell: 4.7 nTPM
naive CD8 T-cell: 3.9 nTPM
memory CD8 T-cell: 3.7 nTPM
naive CD4 T-cell: 3.3 nTPM
memory CD4 T-cell: 3.1 nTPM

Brain region

cerebral cortex: 168 nTPM
pons: 133 nTPM
basal ganglia: 115 nTPM
white matter: 112 nTPM
hypothalamus: 98 nTPM
cerebellum: 96 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GLS.

Disease | AllUniProt

Conditions GLS is implicated in, by any mechanism.

Developmental and epileptic encephalopathy 71 (DEE71) MIM:618328
CASGID syndrome (CASGID) MIM:618339
Global developmental delay, progressive ataxia, and elevated glutamine (GDPAG) MIM:618412

Disease | GeneticClinVar

19 pathogenic / likely-pathogenic of 176 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Developmental and epileptic encephalopathy, 71
Global developmental delay, progressive ataxia, and elevated glutamine
Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development
Esophageal atresia/tracheoesophageal fistula
Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.32
gnomAD pLI: 0.96
gnomAD missense Z: 3.73
DepMap mean gene effect: -0.21
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

glutaminase activity

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of GLS in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads GLS as an antibody target. Whether an autoantibody or antibody against GLS could matter depends on whether native GLS is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

GLS is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label GLS as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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