FMO2 (Flavin Containing Dimethylaniline Monoxygenase 2): Genetics, Function, and Clinical Significance
A comprehensive biomedical overview of the FMO2 gene, including genomic context, expression, mutations, and disease associations.
Gene Information Card
| Symbol | FMO2 |
|---|---|
| Full Name | flavin containing dimethylaniline monoxygenase 2 |
| Gene Type | protein coding |
| Chromosomal Location | 1q24.3 |
| NCBI Gene ID | 2327 ncbi.nlm.nih.gov/gene/2327 |
| Ensembl ID | ENSG00000094914 |
| UniProt ID | Q99518 |
| OMIM ID | 603134 |
| HGNC ID | 3771 |
| Aliases | FMO2, dimethylaniline monooxygenase [N-oxide-forming] 2 |
Description
The FMO2 gene encodes flavin-containing monooxygenase 2 (FMO2), a microsomal enzyme that catalyzes the oxygenation of various xenobiotics, including drugs and environmental toxins. FMO2 is primarily expressed in the lung and kidney, and its activity is critical for the metabolism of compounds containing nucleophilic nitrogen, sulfur, or phosphorus atoms. A common polymorphism (p.Leu236Ser) results in a truncated, inactive protein in many populations, affecting drug metabolism and susceptibility to certain pulmonary diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lung cancer | FMO2 activity may influence the metabolism of tobacco-specific nitrosamines, potentially modulating carcinogen activation or detoxification. The inactive FMO2 variant (p.Leu236Ser) has been associated with altered risk in some studies. | PMID: 20442288; PMID: 23696453 |
| Pulmonary hypertension | FMO2 is expressed in pulmonary endothelial cells and may metabolize endogenous substrates that affect vascular tone. Reduced FMO2 activity could contribute to endothelial dysfunction. | PMID: 21900221 |
| Trimethylaminuria (fish odor syndrome) | Although primarily caused by FMO3 mutations, FMO2 variants may modulate the phenotype due to overlapping substrate specificity. | PMID: 11280720 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.4 | Medium |
| Kidney | 8.1 | Medium |
| Liver | 3.2 | Low |
| Small intestine | 2.5 | Low |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 15.2 | High expression; used for FMO2 functional studies |
| HepG2 (hepatocellular carcinoma) | 4.5 | Moderate expression |
| HEK293 (embryonic kidney) | 2.1 | Low expression; often used for recombinant FMO2 |
| MCF7 (breast carcinoma) | 0.3 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Leu236Ser (c.707T>C) | Missense (creates premature stop codon) | Allele frequency ~0.15 in African/African-American populations; rare in Europeans | Results in truncated, non-functional protein; loss of FMO2 activity |
| p.Pro153Leu (c.458C>T) | Missense | Rare (MAF <0.01) | May affect protein stability; functional impact uncertain |
| p.Arg238* (c.712C>T) | Nonsense | Very rare | Premature termination; loss of function |
Mutation functional classification
Loss of Function (LOF)
The p.Leu236Ser variant is the most common loss-of-function allele, producing a truncated protein lacking the NADPH-binding domain, resulting in complete loss of catalytic activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for FMO2.
Dominant Negative (DN)
No dominant-negative effects have been described; FMO2 is likely haploinsufficient, but heterozygotes may have reduced activity.
View complete mutation data：
Gene Ontology (GO)
| • N (GO:0004499) | • iron ion binding (GO:0005506) |
| • oxidoreductase activity (GO:0016491) | • NADP binding (GO:0050661) |
| • endoplasmic reticulum membrane (GO:0005783) | • microsome (GO:0005792) |
| • xenobiotic metabolic process (GO:0006805) | • oxidation-reduction process (GO:0055114) |
Pathways
• Xenobiotics metabolism (Reactome: R-HSA-211981)
• Drug metabolism - cytochrome P450 (KEGG: hsa00982) - FMO2 is not a P450 but participates in similar pathways
• Metabolism of xenobiotics by cytochrome P450 (KEGG: hsa00980) - FMO2 is often co-regulated
Protein Summary
FMO2 is a 60 kDa microsomal enzyme belonging to the flavin-containing monooxygenase family. It contains a FAD-binding domain and an NADPH-binding domain, and uses NADPH as a cofactor to oxygenate nucleophilic heteroatoms in xenobiotics. The enzyme is anchored to the endoplasmic reticulum membrane via a C-terminal transmembrane domain. FMO2 is highly expressed in the lung, where it plays a role in the metabolism of inhaled toxins and drugs. The common p.Leu236Ser polymorphism leads to a truncated protein that is retained in the ER and degraded, resulting in loss of enzyme activity. This polymorphism is associated with population-specific differences in drug metabolism and disease susceptibility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FMO2 Knockout HEK293 Cell Line | EDJ-KQ4615 | Human | 2327 | Details Get a Quote |
| FMO2 Knockout HeLa Cell Line | EDJ-KQ53254 | Human | 2327 | Details Get a Quote |
| FMO2 Knockout A-549 Cell Line | EDJ-KQ61736 | Human | 2327 | Details Get a Quote |
| FMO2 Knockout HCT 116 Cell Line | EDJ-KQ70223 | Human | 2327 | Details Get a Quote |
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