CausalSentinel

Protein Dossier — VTN (Vitronectin)

MR feasibility tier: C — No plasma pQTL found (accession + symbol match). Standard plasma pQTL MR is not currently feasible; gene-level genetic evidence below is the honest preview.

1. Published MR estimates (retrieved, not computed)

None in the EpiGraphDB pQTL resource. Absence of an estimate is not evidence of no effect.

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

2142 association rows across 1478 traits (2134 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
Vitronectin levels 4e-6996 rs704 2 GCST90250177 no MR -> candidate analysis
MICOS complex subunit MIC10 levels 4e-5900 rs704 1 GCST90248470 no MR -> candidate analysis
MAP kinase-activated protein kinase 5 levels 8e-3943 rs704 1 GCST90248480 no MR -> candidate analysis
Transmembrane protease serine 6 levels 7e-3426 rs704 1 GCST90249925 no MR -> candidate analysis
Methyl-CpG-binding domain protein 1 levels 8e-2008 rs704 1 GCST90248454 no MR -> candidate analysis
MICOS complex subunit MIC10 levels (MINOS1.7956.11.3) 1e-1442 rs704 1 GCST90241930 no MR -> candidate analysis
Blood protein levels 9e-1306 rs704 589 GCST006585 no MR -> candidate analysis
Vitronectin (analyte X13125.45) levels 5e-987 rs704 1 GCST90422096 no MR -> candidate analysis
Carboxypeptidase N subunit 2 levels 2e-846 rs704 2 GCST90246881 no MR -> candidate analysis
Inactive peptidyl-prolyl cis-trans isomerase FKBP6 levels (F 2e-836 rs704 1 GCST90241487 no MR -> candidate analysis
Vitronectin levels (VTN.8280.238.3) 8e-770 rs704 1 GCST90243346 no MR -> candidate analysis
GTP-binding protein GEM levels 2e-688 rs704 1 GCST90247828 no MR -> candidate analysis
…and 1466 more traits (see JSON)          

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 722 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
hypertensive disorder 0.715 common-variant locus no MR -> candidate analysis
temporal arteritis 0.572 common-variant locus no MR -> candidate analysis
age-related macular degeneration 0.426 common-variant locus no MR -> candidate analysis
ventricular septal defect 0.451 common-variant locus no MR -> candidate analysis
COVID-19 0.408 common-variant locus no MR -> candidate analysis
wet macular degeneration 0.3 common-variant locus no MR -> candidate analysis
atrophic macular degeneration 0.3 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 7 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 (Vitronectin)
gnomAD constraint pLI=6.4e-13, LOEUF=1.03 — LoF-tolerant
GWAS Catalog 76 unique SNPs / 152 rows
ClinVar 120 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance