KMO
Chr 1kynurenine 3-monooxygenase
Also known as: dJ317G22.1
The KMO protein is a mitochondrial outer membrane enzyme that catalyzes the hydroxylation of L-kynurenine to form 3-hydroxy-L-kynurenine, which is required for synthesis of quinolinic acid, a neurotoxic compound that affects NMDA receptor signaling during brain development. Mutations cause autosomal recessive developmental delay and seizures, with the gene being loss-of-function intolerant (pLI near 0, LOEUF 0.698). The phenotype involves neurological manifestations affecting brain development, with potential effects on other organ systems including pancreatic, cardiac, and gastrointestinal function.
No known disease relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
153 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 61 | 0 | 61 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 2 | 48 | 19 | 0 | 69 |
Likely Benign | 0 | 6 | 1 | 0 | 7 |
Benign | 0 | 1 | 1 | 1 | 3 |
| Total | 2 | 55 | 85 | 1 | 143 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KMO · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools