FMO5 (Flavin Containing Dimethylaniline Monoxygenase 5): Gene, Function, and Clinical Significance
A comprehensive overview of the FMO5 gene, including its genomic context, protein function, expression patterns, and associated diseases.
Gene Information Card
| Symbol | FMO5 |
|---|---|
| Full Name | flavin containing dimethylaniline monoxygenase 5 |
| Gene Type | protein coding |
| Chromosomal Location | 1q21.1 |
| NCBI Gene ID | 2330 ncbi.nlm.nih.gov/gene/2330 |
| Ensembl ID | ENSG00000131738 |
| UniProt ID | P49326 |
| OMIM ID | 603957 |
| HGNC ID | 3772 |
| Aliases | FMO5 |
Description
FMO5 (flavin containing dimethylaniline monoxygenase 5) is a protein-coding gene located on chromosome 1q21.1. It encodes a member of the flavin-containing monooxygenase (FMO) family, which are microsomal enzymes that catalyze the oxygenation of various xenobiotics and endogenous compounds. FMO5 is expressed in multiple tissues, with highest levels in liver and kidney, and plays a role in drug metabolism and detoxification. Unlike other FMO family members, FMO5 has a distinct substrate specificity, preferentially oxidizing certain nucleophilic heteroatoms. Mutations in FMO5 have been associated with altered drug metabolism and potential susceptibility to certain diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Trimethylaminuria (TMAU) | FMO5 mutations may contribute to reduced N-oxidation of trimethylamine, leading to its accumulation and fishy odor. However, FMO5 is not the primary enzyme; FMO3 is the main contributor. FMO5 variants may modulate the phenotype. | ClinVar: some variants reported; limited direct evidence. |
| Drug metabolism variations | FMO5 polymorphisms can affect the metabolism of drugs such as sulindac sulfide and benzydamine, potentially altering therapeutic efficacy and toxicity. | PubMed studies; ClinVar. |
| Potential cancer susceptibility | Altered FMO5 expression has been observed in certain cancers, but direct causal mutations are not well established. FMO5 may influence metabolism of carcinogens. | COSMIC: somatic mutations in some cancer samples; functional significance unclear. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 20.1 | High |
| Kidney | 12.3 | Medium |
| Small Intestine | 8.5 | Medium |
| Lung | 4.2 | Low |
| Brain | 1.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.0 | Liver cancer cell line; high expression |
| A549 | 3.5 | Lung carcinoma; low expression |
| HEK293 | 2.0 | Embryonic kidney; low expression |
| MCF7 | 1.5 | Breast cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Pro152Leu (rs2014355) | Missense | 0.5% (global) | May alter enzyme activity; clinical significance uncertain. |
| p.Arg253Gln (rs202086642) | Missense | 0.1% | Potential impact on substrate specificity; not well characterized. |
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare | Loss-of-function; may affect drug metabolism. |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein likely result in loss of enzymatic activity, leading to reduced metabolism of FMO5 substrates.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; some missense variants may alter substrate specificity but not necessarily increase activity.
Dominant Negative (DN)
No evidence for dominant-negative effects; FMO5 is likely haploinsufficient, but data are limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004497 (GO:0004497) | • GO:0016709 (GO:0016709) |
| • GO:0050661 (GO:0050661) | • GO:0005789 (GO:0005789) |
| • GO:0016021 (GO:0016021) |
Pathways
• Drug metabolism - cytochrome P450 (shared with FMO)
• Xenobiotics metabolism
• Biological oxidations
Protein Summary
FMO5 is a 533-amino acid microsomal flavoprotein that uses FAD and NADPH to oxygenate nucleophilic nitrogen, sulfur, and phosphorus atoms in various substrates. It is anchored to the endoplasmic reticulum membrane via a C-terminal transmembrane domain. FMO5 has a unique substrate profile compared to other FMOs, including the oxidation of certain drugs and endogenous compounds. Its expression is highest in liver and kidney, and it contributes to the first-pass metabolism of xenobiotics. Structural studies reveal a conserved FAD-binding domain and a NADPH-binding domain, with a catalytic mechanism involving a C4a-hydroperoxyflavin intermediate.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FMO5 Knockout HEK293 Cell Line | EDJ-KQ4620 | Human | 2330 | Details Get a Quote |
| FMO5 Knockout HeLa Cell Line | EDJ-KQ53257 | Human | 2330 | Details Get a Quote |
| FMO5 Knockout A-549 Cell Line | EDJ-KQ61739 | Human | 2330 | Details Get a Quote |
| FMO5 Knockout HCT 116 Cell Line | EDJ-KQ70225 | Human | 2330 | Details Get a Quote |
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