KMO Gene: Kynurenine 3-Monooxygenase
A key enzyme in the tryptophan metabolism pathway, implicated in neurodegenerative, psychiatric, and inflammatory disorders.
Gene Information Card
| Symbol | KMO |
|---|---|
| Full Name | Kynurenine 3-monooxygenase |
| Gene Type | Protein coding |
| Chromosomal Location | 1q42.12 |
| NCBI Gene ID | 5784 ncbi.nlm.nih.gov/gene/5784 |
| Ensembl ID | ENSG00000117020 |
| UniProt ID | Q15219 |
| OMIM ID | 603538 |
| HGNC ID | 6377 |
| Aliases | KMO; dJ317G16.1 |
Description
The KMO gene encodes kynurenine 3-monooxygenase, a mitochondrial outer membrane enzyme that catalyzes the hydroxylation of L-kynurenine to 3-hydroxykynurenine (3-HK) in the kynurenine pathway of tryptophan metabolism. This enzyme is a critical branch point in the pathway, directing the metabolism of tryptophan towards the production of either neurotoxic metabolites (such as quinolinic acid) or neuroprotective metabolites (such as kynurenic acid). KMO is expressed in various tissues, with high levels in the liver, kidney, and immune cells, and its activity is implicated in the pathogenesis of several neurological and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Huntington's Disease | Increased KMO activity in the brain leads to elevated levels of neurotoxic 3-hydroxykynurenine and quinolinic acid, contributing to neuronal cell death and motor dysfunction. | Evidence from post-mortem brain tissue and animal models (e.g., R6/2 mice) shows increased KMO expression and activity. |
| Alzheimer's Disease | Altered kynurenine pathway metabolism, including increased KMO activity, is associated with neuroinflammation and amyloid-beta toxicity, potentially contributing to cognitive decline. | Studies show elevated 3-HK levels in the brain and cerebrospinal fluid of AD patients. |
| Schizophrenia | A shift in the kynurenine pathway towards the neuroprotective branch (kynurenic acid) is observed, which may be due to reduced KMO activity. Elevated kynurenic acid levels are linked to cognitive deficits and glutamatergic hypofunction. | Genetic association studies and post-mortem analyses show altered KMO expression and kynurenic acid levels in patients. |
| Major Depressive Disorder | Inflammation-induced activation of the kynurenine pathway, including KMO, can lead to increased neurotoxic metabolites, contributing to depressive symptoms. | Clinical studies show increased KMO expression and 3-HK levels in depressed patients, particularly those with inflammation. |
| HIV-Associated Neurocognitive Disorders | HIV infection activates the kynurenine pathway in the brain, leading to increased KMO activity and neurotoxic metabolite production, contributing to cognitive impairment. | Studies in HIV patients and animal models show elevated KMO expression and quinolinic acid levels in the brain. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | High |
| Kidney | High | High |
| Placenta | Medium | Medium |
| Lung | Medium | Medium |
| Brain | Low | Low |
| Spleen | Medium | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (Liver) | High | High expression in liver cancer cell line |
| A549 (Lung) | Medium | Moderate expression in lung carcinoma cell line |
| U87 (Glioblastoma) | Low | Low expression in brain cancer cell line |
| THP-1 (Monocyte) | Medium | Expression inducible by inflammatory stimuli |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1053239 | SNP (Intronic) | ~30% (Minor Allele Frequency) | Associated with altered KMO expression and activity; linked to schizophrenia and inflammatory diseases. |
| rs2275163 | SNP (Intronic) | ~20% (Minor Allele Frequency) | Associated with altered kynurenic acid levels and risk for schizophrenia. |
| rs3789476 | SNP (Intronic) | ~15% (Minor Allele Frequency) | Associated with KMO expression levels in immune cells. |
Mutation functional classification
Loss of Function (LOF)
Complete loss-of-function mutations are rare and not well-documented in humans. However, reduced KMO activity is associated with a shift towards kynurenic acid production, which may be neuroprotective but can also lead to cognitive deficits.
Gain of Function (GOF)
Increased KMO activity, often due to inflammatory stimuli or genetic variants that increase expression, leads to elevated levels of neurotoxic metabolites (3-HK and quinolinic acid), contributing to neurodegeneration.
Dominant Negative (DN)
No dominant-negative mutations have been described for KMO.
View complete mutation data：
Gene Ontology (GO)
| • kynurenine 3-monooxygenase activity | • FAD binding |
| • NADPH binding | • mitochondrial outer membrane |
| • kynurenine metabolic process | • tryptophan catabolic process |
| • response to lipopolysaccharide | • cellular response to interferon-gamma |
Pathways
• Tryptophan metabolism
• Kynurenine pathway
• Superpathway of tryptophan utilization
Protein Summary
Kynurenine 3-monooxygenase (KMO) is a 486-amino acid protein localized to the outer mitochondrial membrane. It is a flavoprotein that requires FAD and NADPH as cofactors. The protein consists of a C-terminal catalytic domain and an N-terminal region that anchors it to the membrane. KMO catalyzes the conversion of L-kynurenine to 3-hydroxykynurenine, a rate-limiting step in the kynurenine pathway. Its activity is tightly regulated by cellular redox state and inflammatory cytokines. The protein is a key target for therapeutic intervention in diseases where the kynurenine pathway is dysregulated.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KMO Knockout HEK293 Cell Line | EDJ-KQ6289 | Human | 8564 | Details Get a Quote |
| KMO Knockout HeLa Cell Line | EDJ-KQ54942 | Human | 8564 | Details Get a Quote |
| KMO Knockout A-549 Cell Line | EDJ-KQ63427 | Human | 8564 | Details Get a Quote |
| KMO Knockout HCT 116 Cell Line | EDJ-KQ71893 | Human | 8564 | Details Get a Quote |
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