KYNU

Chr 2AR

kynureninase

Also known as: KYNUU, VCRL2

NCBI Gene: 8942ENSG00000115919UniProt: Q16719

Kynureninase is a pyridoxal-5'-phosphate (pyridoxal-P) dependent enzyme that catalyzes the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic acids, respectively. Kynureninase is involved in the biosynthesis of NAD cofactors from tryptophan through the kynurenine pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

Primary Disease Associations & Inheritance

?HydroxykynureninuriaMIM #236800
AR
Vertebral, cardiac, renal, and limb defects syndrome 2MIM #617661
AR
143
ClinVar variants
43
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— KYNU
🧬
Gene-Disease Validity (ClinGen)
vertebral, cardiac, renal, and limb defects syndrome 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 79 VUS of 143 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.
1.35LOEUF
pLI 0.000
Z-score 0.09
OE 0.98 (0.72–1.35)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.41Z-score
OE missense 1.07 (0.97–1.19)
267 obs / 248.7 exp
Tolerant

Tolerant to missense variation

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.0.98 (0.72–1.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.97–1.19)
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.0.89
0≤1.21.6
LoF obs/exp: 27 / 27.5Missense obs/exp: 267 / 248.7Syn Z: 0.83

ClinVar Variant Classifications

143 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic14
VUS79
Likely Benign12
Benign7
Conflicting2
29
Pathogenic
14
Likely Pathogenic
79
VUS
12
Likely Benign
7
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
5
19
0
29
Likely Pathogenic
4
3
7
0
14
VUS
0
70
8
1
79
Likely Benign
0
3
4
5
12
Benign
0
1
2
4
7
Conflicting
—2
Total9824010143

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KYNU · 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
KYNURENINASE; KYNU
MIM #605197 · *

?Hydroxykynureninuria

MIM #236800

Molecular basis of disorder known

Autosomal recessive

Vertebral, cardiac, renal, and limb defects syndrome 2

MIM #617661

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — KYNU
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Tryptophan Metabolism Acts as a New Anti-Ferroptotic Pathway to Mediate Tumor Growth.
Liu D et al.·Adv Sci (Weinh)
2023
GPX4 knockdown suppresses M2 macrophage polarization in gastric cancer by modulating kynurenine metabolism.
Xu J et al.·Theranostics
2025
NAD Deficiency, Congenital Malformations, and Niacin Supplementation.
Shi H et al.·N Engl J Med
2017
Organ Protection by Caloric Restriction Depends on Activation of the De Novo NAD+ Synthesis Pathway.
Späth MR et al.·J Am Soc Nephrol
2023
Glutathione peroxidase 2 knockdown suppresses gastric cancer progression and metastasis via regulation of kynurenine metabolism.
Xu H et al.·Oncogene
2023
Multi-omics analysis-based clinical and functional significance of a novel prognostic and immunotherapeutic gene signature derived from amino acid metabolism pathways in lung adenocarcinoma.
Xiang H et al.·Front Immunol
2024Functional
Two new cases of KYNU deficiency: Further delineation of the phenotypic and biochemical spectrum and exploration of treatment options.
Goorden SMI et al.·Mol Genet Metab
2025Case report
The Kynurenine Pathway in Psoriasis: Mechanisms and Therapeutic Opportunities.
Huang S et al.·Inflammation
2025Review
Re-sequencing of candidate genes FOXF1, HSPA6, HAAO, and KYNU in 522 individuals with VATER/VACTERL, VACTER/VACTERL-like association, and isolated anorectal malformation.
Thiem CE et al.·Birth Defects Res
2022
A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder.
Szot JO et al.·J Clin Invest
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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