KMO

Chr 1

kynurenine 3-monooxygenase

Also known as: dJ317G22.1

NCBI Gene: 8564ENSG00000117009UniProt: O15229

This gene encodes a mitochondrion outer membrane protein that catalyzes the hydroxylation of L-tryptophan metabolite, L-kynurenine, to form L-3-hydroxykynurenine. Studies in yeast identified this gene as a therapeutic target for Huntington disease. [provided by RefSeq, Oct 2011]

153
ClinVar variants
64
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— KMO
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
64 Pathogenic / Likely Pathogenic· 69 VUS of 153 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.70LOEUF
pLI 0.000
Z-score 2.79
OE 0.43 (0.28–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.83Z-score
OE missense 0.68 (0.60–0.77)
180 obs / 263.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.43 (0.28–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.60–0.77)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.19
0≤1.21.6
LoF obs/exp: 12 / 27.9Missense obs/exp: 180 / 263.4Syn Z: -1.40

ClinVar Variant Classifications

153 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic3
VUS69
Likely Benign7
Benign3
61
Pathogenic
3
Likely Pathogenic
69
VUS
7
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
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
Total255851143

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Molecular mechanisms and therapeutic significance of Tryptophan Metabolism and signaling in cancer.
Yan J et al.·Mol Cancer
2024Review
Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond.
Platten M et al.·Nat Rev Drug Discov
2019Review
Tryptophan metabolites modulate inflammatory bowel disease and colorectal cancer by affecting immune system.
Ala M·Int Rev Immunol
2022Review
Gene Variant Frequencies of IDO1, IDO2, TDO, and KMO in Substance Use Disorder Cohorts.
Contella L et al.·Genes (Basel)
2024Cohort
Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.
Pocivavsek A et al.·Pharmacol Rev
2024Review
Kynurenines as a Novel Target for the Treatment of Inflammatory Disorders.
Mor A et al.·Cells
2024Review
The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors.
Hughes TD et al.·Molecules
2022Review
Mitochondrial-related genes as prognostic and metastatic markers in breast cancer: insights from comprehensive analysis and clinical models.
Fang Y et al.·Front Immunol
2024Functional
The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression.
Lavebratt C et al.·Mol Psychiatry
2014
[Biomarker in gynecologic malignancies].
Isonishi S·Gan To Kagaku Ryoho
2004Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Host kynurenine monooxygenase (KMO) serves as a critical immune defense factor restricting Toxoplasma gondii proliferation.
Tang SJ et al.·Acta Trop
2026
KMO downregulation promotes hepatocellular carcinoma growth via 3‑HAA‑mediated mitochondrial mass and function imbalances.
Liu M et al.·Int J Oncol
2026🔓 Open Access
Renal and hepatic function is preserved following inducible knockout of kynurenine pathway enzymes KMO or QPRT in adult mice.
Summers BS et al.·PLoS One
2025🔓 Open Access
Multi-tapered optical fiber-based plasmonic biosensor with KMO nanoflowers and MWCNTs for highly sensitive detection of tetrodotoxin in real food samples.
Liu W et al.·Opt Express
2025
Kmo restricts Salmonella in a whole organism infection model by promoting macrophage lysosomal acidification through kainate receptor antagonism.
Goering ER et al.·PLoS Pathog
2025🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Schizophrenia

Tryptophan-Kynurenine Pathway Metabolism in the Pathophysiology of Cognitive Impairment in Schizophrenia.

ENROLLING BY INVITATION
NCT07162467Tianjin Anding HospitalStarted 2024-02-19

External Resources

Links to major genomics databases and tools