GLS

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]

Glutaminase

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, the main excitatory neurotransmitter in the brain (PubMed:30575854, PubMed:30239721, PubMed:30970188).

Isoform 2:
Lacks catalytic activity.

Chemical synaptic transmission Source: Ensembl
Glutamate biosynthetic process Source: UniProtKB
Glutamate homeostasis Source: UniProtKB
Glutamine catabolic process Source: UniProtKB
Protein homotetramerization Source: UniProtKB
Regulation of respiratory gaseous exchange by nervous system process Source: Ensembl
Suckling behavior Source: Ensembl

Isoform 1: Mitochondrion; Cytosol. The 74-kDa cytosolic precursor is translocated into the mitochondria and processed via a 72-kDa intermediate to yield the mature 68- and 65-kDa subunits.
Isoform 3: Mitochondrion; Mitochondrion matrix. Produced by the proteolytic processing of the 74-kDa cytosolic precursor.
Mitochondrion matrix. Produced by the proteolytic processing of the 74-kDa cytosolic precursor.

Developmental and epileptic encephalopathy 71 (DEE71):
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE71 is an autosomal recessive form with onset at birth. Death occurs in first weeks of life.
Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development (CASGID):
An autosomal dominant disease characterized by infantile-onset cataract, erythematic subcutaneous nodules, profound developmental delay, self-injurious behavior, and intracerebral glutamate excess. Histopathologic analysis of skin lesions show deep perivascular and periglandular lymphohistiocytic infiltrates and pronounced leukocytoclasia at the surface of the dermis, focal vacuolar alterations, hyperkeratosis, and parakeratosis of the epidermis.
Global developmental delay, progressive ataxia, and elevated glutamine (GDPAG):
An autosomal recessive disease characterized by early-onset delay in motor skills, delayed speech, progressive ataxia, and neurologic deterioration. Plasma glutamine is persistently elevated by a factor of 2.5 despite normal plasma ammonia levels.

Synthesized as a 74-kDa cytosolic precursor which is proteolytically processed by the mitochondrial-processing peptidase (MPP) via a 72-kDa intermediate to yield the mature mitochondrial 68- and 65-kDa subunits.