Protein Dossier — PLAU (Urokinase-type plasminogen activator)
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 |
| Crohn’s disease |
-0.408 |
0.0565 |
4.72e-13 |
Wald ratio |
1 |
cis |
1 |
| Inflammatory bowel disease |
-0.281 |
0.0463 |
1.28e-09 |
Wald ratio |
1 |
cis |
0.996 |
| Years of schooling |
0.0575 |
0.0164 |
4.65e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypothyroidism or myxoedema |
-0.138 |
0.0443 |
0.00178 |
Inverse variance weighted |
2 |
trans |
NA |
| Non-cancer illness code self-reported: hypothyroidism or myxoedema |
-0.138 |
0.0443 |
0.00178 |
Inverse variance weighted |
2 |
cis |
NA |
| Cancer code self-reported: malignant melanoma |
0.232 |
0.0784 |
0.00309 |
Inverse variance weighted |
2 |
trans |
NA |
| Cancer code self-reported: malignant melanoma |
0.232 |
0.0784 |
0.00309 |
Inverse variance weighted |
2 |
cis |
NA |
| Diagnoses - main ICD10: R14 Flatulence and related conditions |
0.6 |
0.208 |
0.00395 |
Inverse variance weighted |
2 |
trans |
NA |
| Diagnoses - main ICD10: R14 Flatulence and related conditions |
0.6 |
0.208 |
0.00395 |
Inverse variance weighted |
2 |
cis |
NA |
| Diagnoses - main ICD10: N81 Female genital prolapse |
0.168 |
0.0614 |
0.00637 |
Inverse variance weighted |
2 |
trans |
NA |
| Diagnoses - main ICD10: N81 Female genital prolapse |
0.168 |
0.0614 |
0.00637 |
Inverse variance weighted |
2 |
cis |
NA |
| Juvenile idiopathic arthritis |
0.641 |
0.24 |
0.00744 |
Wald ratio |
1 |
cis |
NA |
| …and 180 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4158_54_2 |
uPA |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
29 association rows across 19 traits (28 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 |
| Circulating PLAU levels (id: OID00631_OID21124) |
6e-192 |
rs55744193 |
2 |
GCST90859976 |
no MR -> candidate analysis |
| Circulating PLAU levels (id: OID00481_OID21124) |
6e-155 |
rs55744193 |
2 |
GCST90859841 |
no MR -> candidate analysis |
| Urokinase-type plasminogen activator levels |
1e-116 |
rs2227560 |
2 |
GCST90250110 |
no MR -> candidate analysis |
| PLAU protein levels |
5e-116 |
rs55744193 |
3 |
GCST90470252 |
no MR -> candidate analysis |
| Serum levels of protein PLAU |
2e-96 |
rs55744193 |
2 |
GCST90088614 |
no MR -> candidate analysis |
| Circulating PLAUR levels |
6e-94 |
rs4065 |
2 |
GCST90859965 |
no MR -> candidate analysis |
| PLAUR protein levels |
3e-74 |
rs2227566 |
1 |
GCST90470251 |
no MR -> candidate analysis |
| Blood protein levels |
4e-50 |
rs2227564 |
2 |
GCST006585 |
no MR -> candidate analysis |
| Serum levels of protein KAZALD1 |
2e-36 |
rs2227551 |
1 |
GCST90089691 |
no MR -> candidate analysis |
| Kazal-type serine protease inhibitor domain-containing prote |
4e-29 |
rs61567551 |
1 |
GCST90248166 |
no MR -> candidate analysis |
| Urokinase-type plasminogen activator levels (PLAU.4158.54.2) |
5e-20 |
rs2227551 |
2 |
GCST90243298 |
no MR -> candidate analysis |
| Crohn’s disease |
5e-13 |
rs2227551 |
2 |
GCST003044 |
MR: beta=-0.408, p=4.72e-13 (cis) |
| …and 7 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 1267 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 |
| Quebec platelet disorder |
0.549 |
— |
established (curated) |
no MR -> candidate analysis |
| abdominal aortic aneurysm |
0.819 |
— |
common-variant locus |
no MR -> candidate analysis |
| inflammatory bowel disease |
0.734 |
— |
common-variant locus |
MR: beta=-0.281, p=1.28e-09 (cis) |
| atherosclerosis |
0.561 |
— |
common-variant locus |
no MR -> candidate analysis |
| actinic keratosis |
0.547 |
— |
common-variant locus |
no MR -> candidate analysis |
| psoriasis vulgaris |
0.532 |
— |
common-variant locus |
no MR -> candidate analysis |
| Alzheimer disease type 1 |
0.243 |
— |
established (curated) |
no MR -> candidate analysis |
| psoriasis |
0.2 |
— |
common-variant locus |
no MR -> candidate analysis |
| type 2 diabetes mellitus |
0.196 |
— |
common-variant locus |
no MR -> candidate analysis |
| Crohn disease |
0.177 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 10 rows above, 9 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 |
1 known modulators (Urokinase-type plasminogen activator) |
| gnomAD constraint |
pLI=1.8e-07, LOEUF=0.879 — LoF-tolerant |
| GWAS Catalog |
67 unique SNPs / 134 rows |
| ClinVar |
183 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1267 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 ‘PLAU’ and resolved to ‘Urokinase-type plasminogen activator’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 183 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 19 of 19 traits by best p-value, aggregated from 29 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/P00749 — 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/ENSG00000122861/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3286/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PLAU — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PLAU — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PLAU%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/PLAU — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:25:22 · 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