KYNU

Chr 2AR

kynureninase

Also known as: KYNUU, VCRL2

NCBI Gene: 8942 ENSG00000115919 UniProt: Q16719 OMIM: 605197

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 OMIM 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 OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?HydroxykynureninuriaMIM #236800

Vertebral, cardiac, renal, and limb defects syndrome 2MIM #617661

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · vertebral, cardiac, renal, and limb defects syndrome 2 · AR · ClinGen 2022

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.35

LOEUF

Mechanism· predicted

📖

GeneReview available — KYNU

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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

Background carrier burden — how many people carry a rare variant somewhere in KYNU?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 81

658 rare PASS variants

Rare truncating (LoF)

1 in 640

132 rare PASS variants

Rare synonymous (reference)

1 in 250

205 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KYNU. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 97	1 in 600
South Asian	~43k	1 in 80	1 in 830
Remaining (unassigned)	~30k	1 in 71	1 in 910
European (Finnish)	~27k	1 in 250	1 in 2,000
Admixed American	~22k	1 in 110	1 in 1,400
African / African American	~21k	1 in 120	1 in 640
East Asian	~20k	1 in 95	1 in 350
Ashkenazi Jewish	~13k	1 in 720	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 140	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 13 coding exons well covered in gnomAD exomes; exons 4, 5, 6, 7, 9, 11 marginal. Genomes: all 13.? see exons ↓