LTC4S
protein-codingleukotriene C4 synthase
Gene summary
The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family includes a number of human proteins, several of which are involved the production of leukotrienes. This gene encodes an enzyme that catalyzes the first step in the biosynthesis of cysteinyl leukotrienes, potent biological compounds derived from arachidonic acid. Leukotrienes have been implicated as mediators of anaphylaxis and inflammatory conditions such as human bronchial asthma. This protein localizes to the nuclear envelope and adjacent endoplasmic reticulum. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: Pharmacogenomic
Rationale: The relative risk/odds ratios of identified variants are overall relatively low, but variants may have pharmacogenomic importance
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LTC4S variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_145867.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 17 | 17 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 19 | 0 | 1 | 20 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_665874.1 | 5 | MANE Select | |
| Ensembl | ENSP00000292596.10 | 5 | MANE Select | |
| Ensembl | ENSP00000385627.3 | 3 | Standard | |
| Ensembl | ENSP00000385627.3 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Arachidonic acid metabolism - Homo sapiens (human)
- Leukotriene modifiers pathway, Pharmacodynamics
- Etodolac Action Pathway
- Ketoprofen Action Pathway
- Ibuprofen Action Pathway
Biological Process
- leukotriene metabolic process
- leukotriene biosynthetic process
- long-chain fatty acid biosynthetic process
- positive regulation of catalytic activity
- cellular oxidant detoxification
Molecular Function
- glutathione transferase activity
- leukotriene-C4 synthase activity
- glutathione peroxidase activity
- protein binding
- enzyme activator activity
Cellular Component
- nuclear envelope
- nuclear outer membrane
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000292596
- Coding exons
- 5
- Length
- 2668
- Individuals with no LoFs
- 125020
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 518
- Defined
- 125539
- p
- 0.00207
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.132 | 72 | 68.9 | 1.04 | 0.00000323 | 892 |
| Missense (PolyPhen) | 32 | 29.749 | 1.0757 | 346 | ||
| Synonymous | -0.810 | 43 | 36.8 | 1.17 | 0.00000180 | 348 |
| Loss of Function | 0.439 | 5 | 6.18 | 0.809 | 2.63e-7 | 75 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00058 | 0.00049 | rare |
| Latino/Admixed American | 0.00062 | 0.00061 | rare |
| Ashkenazi Jewish | 0.013 | 0.012 | notable |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0.0021 | 0.0018 | notable |
| European (Non-Finnish) | 0.0028 | 0.0025 | notable |
| South Asian | 0.0014 | 0.0013 | notable |
| Other | 0.0012 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4.;
Recessive Scores
- pRec
- 0.108
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.934
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |