GCLC encodes glutamate-cysteine ligase catalytic subunit (637 aa). Catalyzes the ATP-dependent ligation of L-glutamate and L-cysteine and participates in the first and rate-limiting step in glutathione biosynthesis Highest expression in Bladder (33.0 TPM) and Spleen (27.6 TPM).

Gamma-glutamylcysteine synthetase deficiency is associated with mutations in the GCLC gene on chromosome 6.

The GCLC protein participates in Response to metal ions pathway.

GCLC is classified as a druggable target (Druggable Genome and Enzyme categories) with score 2.6.

Gamma-glutamylcysteine synthetase deficiency is included in newborn screening programs (Galactokinase Deficiency) in 11 states.

Genetic testing for GCLC is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 4 always present features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

No clinical trials have been registered for gamma-glutamylcysteine synthetase deficiency.

10 publications have been identified in PubMed for gamma-glutamylcysteine synthetase deficiency. Research spans Basic Science / Preclinical (40%), Case Report / Case Series (20%), and Clinical Trial Publication (20%).

Recent Publications

• He J (2025). [PMID: 39859401](https://pubmed.ncbi.nlm.nih.gov/39859401/). *Int J Mol Sci*. [Basic Science / Preclinical]

• Naamansen AB (2025). [PMID: 39651840](https://pubmed.ncbi.nlm.nih.gov/39651840/). *American journal of hematology*. [Epidemiology / Natural History]

• Ma TY (2025). [PMID: 41463922](https://pubmed.ncbi.nlm.nih.gov/41463922/). *Animals : an open access journal from MDPI*. [Case Report / Case Series]

• Haimi M (2025). [PMID: 40277844](https://pubmed.ncbi.nlm.nih.gov/40277844/). *Hematology reports*. [Case Report / Case Series]

• Kuo KHM (2024). [PMID: 38712615](https://pubmed.ncbi.nlm.nih.gov/38712615/). *American journal of hematology*. [Clinical Trial Publication]

• O'Shaughnessy S (2024). [PMID: 39544255](https://pubmed.ncbi.nlm.nih.gov/39544255/). *Immunometabolism (Cobham)*. [Basic Science / Preclinical]

• Glenthøj A (2024). [PMID: 39118415](https://pubmed.ncbi.nlm.nih.gov/39118415/). *British journal of haematology*. [Epidemiology / Natural History]

• Glenthøj A (2024). [PMID: 39079928](https://pubmed.ncbi.nlm.nih.gov/39079928/). *BMJ open*. [Clinical Trial Publication]

• Al-Hatou M (2024). [PMID: 39359943](https://pubmed.ncbi.nlm.nih.gov/39359943/). *Molecular syndromology*. [Basic Science / Preclinical]

• Bartnik M (2024). [PMID: 39766843](https://pubmed.ncbi.nlm.nih.gov/39766843/). *Genes*. [Basic Science / Preclinical]