LTC4S Gene - Leukotriene C4 Synthase | Function, Mutations & Disease

LTC4S encodes leukotriene C4 synthase, an integral membrane protein that conjugates leukotriene A4 with reduced glutathione to form leukotriene C4. This enzyme is a key component of the 5-lipoxygenase pathway and is primarily expressed in eosinophils, mast cells, and macrophages. LTC4S activity is critical for the biosynthesis of cysteinyl leukotrienes (LTC4, LTD4, LTE4), which are potent mediators of bronchoconstriction, vascular permeability, and inflammation. Genetic variants in LTC4S have been associated with asthma susceptibility and response to leukotriene receptor antagonists.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Leukotriene biosynthesis (Reactome: R-HSA-2142691)

• Arachidonic acid metabolism (KEGG: hsa00590)

• Metabolism of lipids and lipoproteins (Reactome: R-HSA-556833)

Leukotriene C4 synthase (LTC4S) is a 150-amino acid integral membrane protein localized to the nuclear envelope and endoplasmic reticulum. It belongs to the MAPEG (membrane-associated proteins in eicosanoid and glutathione metabolism) family. The enzyme catalyzes the conjugation of leukotriene A4 with glutathione to form leukotriene C4, the first committed step in cysteinyl leukotriene synthesis. LTC4S exists as a homotrimer and requires Mg2+ for activity. Its expression is regulated by cytokines (e.g., IL-4, IL-13) and transcription factors such as GATA-1. Structural studies reveal a four-helix bundle architecture with a glutathione-binding site. LTC4S is a therapeutic target for asthma and allergic inflammation; inhibitors such as zafirlukast and montelukast target downstream receptors rather than the enzyme itself.