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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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LTC4S
leukotriene C4 synthase
Chromosome 5 · 5q35.3
NCBI Gene: 4056Ensembl: ENSG00000213316.11HGNC: HGNC:6719UniProt: Q16873
99PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
leukotriene-C4 synthase activitynuclear envelopeendoplasmic reticulumnuclear membraneAbnormality of the skeletal systemGenu varumGenu valgumasthma, nasal polyps, and aspirin intolerance
✦AI Summary

LTC4S (leukotriene C4 synthase) is a membrane-bound enzyme that catalyzes the conjugation of leukotriene A4 with glutathione to produce leukotriene C4, a critical inflammatory mediator 1. The enzyme is highly expressed in mast cells, where over 95% of bronchial mast cells express high levels of LTC4S, making them the dominant cellular source rather than eosinophils 1. Beyond classical leukotriene biosynthesis, LTC4S also produces resolution-phase mediators by converting epoxide precursors to specialized proresolving molecules like MCTR1 and RCTR1, which have anti-inflammatory and tissue regeneration properties 23. The enzyme plays a significant role in asthma pathogenesis, with genetic polymorphisms in the LTC4S gene (-444A/C) showing associations with asthma risk in specific populations, particularly Caucasians and aspirin-tolerant individuals 4. In aspirin-exacerbated respiratory disease (AERD), LTC4S overexpression contributes to excessive cysteinyl leukotriene production 5. Clinically, higher densities of LTC4S-positive mast cells correlate with reduced lung function and greater bronchial reversibility in asthma patients 1, making LTC4S both a therapeutic target for anti-inflammatory drugs and a potential biomarker for asthma severity.

Sources cited
1
LTC4S catalyzes leukotriene C4 production and is highly expressed in bronchial mast cells (>95%) rather than eosinophils, correlating with lung function and bronchial reversibility
PMID: 12816731
2
LTC4S produces specialized proresolving mediators MCTR1 and PCTR1 from epoxide precursors, contributing to resolution of inflammation
PMID: 31589826
3
LTC4S converts 7,8(S,S)-epoxytetraene intermediate to RCTR1 in human macrophages and neutrophils
PMID: 39236243
4
The -444A/C polymorphism in LTC4S gene is associated with asthma risk in Caucasians and aspirin-tolerant populations
PMID: 22884858
5
LTC4S overexpression contributes to excessive cysteinyl leukotriene production in aspirin-exacerbated respiratory disease
PMID: 25590316
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.29Weak
Genu valgumOpen Targets
0.27Weak
Genu varumOpen Targets
0.27Weak
asthma, nasal polyps, and aspirin intoleranceOpen Targets
0.12Weak
hypotonia-failure to thrive-microcephaly syndromeOpen Targets
0.12Weak
neoplasmOpen Targets
0.10Weak
lung adenocarcinomaOpen Targets
0.07Suggestive
chronic myelogenous leukemiaOpen Targets
0.05Suggestive
autoimmune diseaseOpen Targets
0.05Suggestive
immune system diseaseOpen Targets
0.05Suggestive
type II hypersensitivity reaction diseaseOpen Targets
0.05Suggestive
dermatitis herpetiformis, familialOpen Targets
0.05Suggestive
pruritus, hereditary localizedOpen Targets
0.05Suggestive
Alzheimer diseaseOpen Targets
0.05Suggestive
C1 inhibitor deficiencyOpen Targets
0.05Suggestive
idiopathic membranous glomerulonephritisOpen Targets
0.05Suggestive
Morvan syndromeOpen Targets
0.05Suggestive
pemphigus vulgarisOpen Targets
0.05Suggestive
Hashimoto's thyroiditisOpen Targets
0.04Suggestive
Autosomal recessive systemic lupus erythematosusOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GGT1Protein interaction92%GGT5Protein interaction92%LTB4R2Protein interaction89%PTGESProtein interaction87%ALOX5APProtein interaction81%CYSLTR1Protein interaction79%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
23%
Ovary
4%
Lung
3%
Brain
0%
Liver
0%
Gene Interaction Network
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LTC4SGGT1GGT5LTB4R2PTGESALOX5APCYSLTR1
PROTEIN STRUCTURE
Preparing viewer…
PDB3PCV · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.68LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.14 [0.79–1.68]
RankingsWhere LTC4S stands among ~20K protein-coding genes
  • #4,844of 20,598
    Most Researched99 · top quartile
  • #16,005of 17,882
    Most Constrained (LOEUF)1.68
Genes detectedLTC4S
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The -444A/C polymorphism in the LTC4S gene and the risk of asthma: a meta-analysis.
PMID: 22884858
Arch Med Res · 2012
1.00
2
Pharmacogenetics of asthma.
PMID: 19077707
Curr Opin Pulm Med · 2009
0.90
3
Biosynthesis of resolvin D1, resolvin D2, and RCTR1 from 7,8(S,S)-epoxytetraene in human neutrophils and macrophages.
PMID: 39236243
Proc Natl Acad Sci U S A · 2024
0.80
4
Common structural and pharmacophoric features of mPGES-1 and LTC4S.
PMID: 29355395
Future Med Chem · 2018
0.70
5
Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthma.
PMID: 12728163
Thorax · 2003
0.60