Protein Dossier — KYNU (Kynureninase)
MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
1. Published MR estimates (retrieved, not computed)
| Outcome |
beta |
se |
p |
method |
nSNP |
cis/trans |
coloc |
| Forced vital capacity (FVC) |
-0.0105 |
0.00246 |
1.87e-05 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0102 |
0.0026 |
8.52e-05 |
Wald ratio |
1 |
cis |
NA |
| Heel bone mineral density (BMD) T-score automated |
-0.0144 |
0.00389 |
2.22e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: asthma |
0.0301 |
0.00816 |
2.27e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hayfever or allergic rhinitis |
0.041 |
0.0118 |
5.37e-04 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K44 Diaphragmatic hernia |
0.0726 |
0.0223 |
0.00116 |
Wald ratio |
1 |
cis |
NA |
| Weight |
-0.0079 |
0.00265 |
0.00288 |
Wald ratio |
1 |
cis |
NA |
| Eye problems or disorders: Cataract |
0.0425 |
0.0158 |
0.00703 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypothyroidism or myxoedema |
0.0344 |
0.0129 |
0.00754 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: depression |
0.0281 |
0.012 |
0.0194 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R35 Polyuria |
0.101 |
0.0435 |
0.0198 |
Wald ratio |
1 |
cis |
NA |
| Alcohol intake frequency |
0.0102 |
0.00444 |
0.0217 |
Wald ratio |
1 |
cis |
NA |
| …and 98 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4559_64_2 |
KYNU |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
99 association rows across 44 traits (91 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.
| Trait |
best p |
lead SNP |
n assoc |
study |
MR status |
| Kynureninase levels |
1e-519 |
rs73961713 |
7 |
GCST90248219 |
no MR -> candidate analysis |
| Circulating KYNU levels |
1e-372 |
rs6711280 |
5 |
GCST90859740 |
no MR -> candidate analysis |
| Bone mineral density mean |
1e-300 |
rs71423227 |
21 |
GCST90321120 |
no MR -> candidate analysis |
| Serum levels of protein KYNU |
1e-145 |
rs12477146 |
1 |
GCST90088740 |
no MR -> candidate analysis |
| DCXR/KYNU protein level ratio |
2e-124 |
rs17808482 |
1 |
GCST90314438 |
no MR -> candidate analysis |
| KYNU protein levels |
4e-123 |
rs17808482 |
3 |
GCST90469722 |
no MR -> candidate analysis |
| Blood protein levels |
7e-83 |
rs3768844 |
1 |
GCST006585 |
no MR -> candidate analysis |
| Kynureninase levels (KYNU.4559.64.2) |
2e-58 |
rs3816193 |
1 |
GCST90241721 |
no MR -> candidate analysis |
| Hematological traits (multi-trait analysis) |
2e-57 |
rs7607734 |
3 |
GCST90838671 |
no MR -> candidate analysis |
| Protein quantitative trait loci |
5e-41 |
rs3768844 |
1 |
GCST010900 |
no MR -> candidate analysis |
| X-15503 levels |
1e-40 |
rs354687 |
6 |
GCST90245602 |
no MR -> candidate analysis |
| Lymphocyte count (UKB data field 30120) |
2e-39 |
rs74847330 |
1 |
GCST90468082 |
no MR -> candidate analysis |
| …and 32 more traits (see JSON) |
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4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 1349 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.
| Disease |
genetic assoc. |
burden (ExWAS) |
causal status |
MR status |
| vertebral, cardiac, renal, and limb defects syndrome 2 |
0.837 |
— |
established (curated) |
no MR -> candidate analysis |
| congenital vertebral-cardiac-renal anomalies syndrome |
0.804 |
— |
established (curated) |
no MR -> candidate analysis |
| encephalopathy due to hydroxykynureninuria |
0.669 |
— |
established (curated) |
no MR -> candidate analysis |
| Catel-Manzke syndrome |
0.796 |
— |
established (curated) |
no MR -> candidate analysis |
| cataract |
0.66 |
— |
common-variant locus |
MR: beta=0.0425, p=0.00703 (cis) |
| pulmonary vascular congestion |
0.536 |
— |
common-variant locus |
no MR -> candidate analysis |
| macular degeneration |
0.501 |
— |
common-variant locus |
no MR -> candidate analysis |
| respiratory system disorder |
0.447 |
— |
common-variant locus |
no MR -> candidate analysis |
| malunion fracture |
0.427 |
— |
common-variant locus |
no MR -> candidate analysis |
| placental abruption |
0.419 |
— |
common-variant locus |
no MR -> candidate analysis |
| transient ischemic attack |
0.408 |
— |
common-variant locus |
no MR -> candidate analysis |
| lens disorder |
0.409 |
— |
common-variant locus |
no MR -> candidate analysis |
| Age-related cataract |
0.409 |
— |
common-variant locus |
no MR -> candidate analysis |
| injury |
0.396 |
— |
common-variant locus |
no MR -> candidate analysis |
| ovarian neoplasm |
0.396 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 14 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.
5. Downstream annotation (druggability & safety preview)
| Layer |
Result |
| ChEMBL druggability |
0 known modulators (Kynureninase) |
| gnomAD constraint |
pLI=2.8e-17, LOEUF=1.14 — LoF-tolerant |
| GWAS Catalog |
93 unique SNPs / 186 rows |
| ClinVar |
162 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1349 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘KYNU’ and resolved to ‘Kynureninase’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 162 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 44 traits by best p-value, aggregated from 99 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/Q16719 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000115919/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL5100/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/KYNU — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/KYNU — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=KYNU%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/KYNU — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:26:48 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none