Protein Dossier — PLAT (Tissue-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 |
| Diagnoses - main ICD10: N81 Female genital prolapse |
0.265 |
0.0923 |
0.00412 |
Wald ratio |
1 |
cis |
NA |
| Caudate volume |
-83.5 |
33.2 |
0.0117 |
Wald ratio |
1 |
cis |
NA |
| Low grade serous ovarian cancer |
0.808 |
0.329 |
0.014 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M54 Dorsalgia |
0.212 |
0.0904 |
0.0188 |
Wald ratio |
1 |
cis |
NA |
| Rheumatoid arthritis |
-0.286 |
0.123 |
0.0204 |
Wald ratio |
1 |
cis |
NA |
| Weight |
-0.0286 |
0.0126 |
0.023 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Ankle |
0.224 |
0.0985 |
0.0232 |
Wald ratio |
1 |
cis |
NA |
| Putamen volume |
-88.2 |
40.9 |
0.0309 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal |
0.202 |
0.0996 |
0.0423 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: G47 Sleep disorders |
0.285 |
0.143 |
0.0464 |
Wald ratio |
1 |
cis |
NA |
| Thalamus volume |
-82.5 |
42.2 |
0.0508 |
Wald ratio |
1 |
cis |
NA |
| Melanoma |
-0.674 |
0.348 |
0.0526 |
Wald ratio |
1 |
cis |
NA |
| …and 86 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2212_69_1 |
tPA |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
9 association rows across 8 traits (7 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 PLAT levels |
1e-52 |
rs8178885 |
1 |
GCST90859980 |
no MR -> candidate analysis |
| PLAT protein levels |
2e-51 |
rs2020921 |
1 |
GCST90470250 |
no MR -> candidate analysis |
| Tissue-type plasminogen activator levels |
3e-43 |
rs8178885 |
2 |
GCST90249945 |
no MR -> candidate analysis |
| Height |
1e-26 |
rs2020922 |
1 |
GCST90245848 |
MR: beta=-0.0291, p=0.0568 (cis) |
| Plasma plasminogen activator levels |
2e-8 |
rs2020921 |
1 |
GCST002374 |
no MR -> candidate analysis |
| Systemic lupus erythematosus |
3e-8 |
rs1804182 |
1 |
GCST005752 |
no MR -> candidate analysis |
| Hair color |
9e-8 |
rs2070711 |
1 |
GCST007082 |
no MR -> candidate analysis |
| Carboxyethyl-GABA levels in elite athletes |
7e-6 |
rs3020640 |
1 |
GCST90133545 |
no MR -> candidate analysis |
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 1921 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 |
| pulmonary embolism |
0.195 |
— |
established (curated) |
MR: beta=-0.446, p=0.0977 (cis) |
| placental abruption |
0.564 |
— |
common-variant locus |
no MR -> candidate analysis |
| preeclampsia |
0.468 |
— |
common-variant locus |
no MR -> candidate analysis |
| memory impairment |
0.466 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 4 rows above, 3 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 |
8 known modulators (Tissue-type plasminogen activator) |
| gnomAD constraint |
pLI=2.3e-10, LOEUF=0.816 — LoF-tolerant |
| GWAS Catalog |
19 unique SNPs / 38 rows |
| ClinVar |
178 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1921 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 ‘PLAT’ and resolved to ‘Tissue-type plasminogen activator’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 178 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 8 of 8 traits by best p-value, aggregated from 9 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/P00750 — 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/ENSG00000104368/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL1873/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PLAT — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PLAT — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PLAT%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/PLAT — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:25:01 · 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