KYNU

Chr 2

kynureninase

Also known as: KYNUU, VCRL2

NCBI Gene: 8942 ENSG00000115919 UniProt: Q16719

Kynureninase catalyzes the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic acids in the tryptophan-to-NAD biosynthesis pathway. Autosomal recessive mutations cause hydroxykynureninuria and vertebral, cardiac, renal, and limb defects syndrome 2, affecting multiple organ systems including the skeletal, cardiovascular, and genitourinary systems.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

DNmechanismLOEUF 1.35

Clinical Summary— KYNU

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Gene-Disease Validity (ClinGen)

vertebral, cardiac, renal, and limb defects syndrome 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

24 unique Pathogenic / Likely Pathogenic· 72 VUS of 133 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — KYNU

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.41Z-score

OE missense 1.07 (0.97–1.19)

267 obs / 248.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.98 (0.72–1.35)

0≤0.351.4

Missense OE?1.07 (0.97–1.19)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 27 / 27.5Missense obs/exp: 267 / 248.7Syn Z: 0.83

This gene — mechanism propensity

0.6259th %ile

GOF

0.5071th %ile

LOF

0.3940th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

133 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic13

VUS72

Likely Benign11

Benign7

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	4	1	0	11
Likely Pathogenic	8	5	0	0	13
VUS	0	71	0	1	72
Likely Benign	0	3	3	5	11
Benign	0	1	2	4	7
Conflicting	—				2
Total	14	84	6	10	116

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap KYNU — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →