CausalSentinel

Protein Dossier — PIR (Pirin)

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: N20 Calculus of kidney and ureter 0.104 0.0412 0.0116 Wald ratio 1 trans NA
Non-cancer illness code self-reported: gout -0.0823 0.035 0.0187 Wald ratio 1 trans NA
Non-cancer illness code self-reported: pernicious anaemia 0.143 0.0616 0.0206 Wald ratio 1 trans NA
Body fat 0.0192 0.00856 0.0253 Wald ratio 1 trans NA
Hirschsprung’s disease 0.453 0.233 0.0523 Wald ratio 1 trans NA
Neo-neuroticism -0.289 0.149 0.0527 Wald ratio 1 trans NA
Neo-agreeableness 0.186 0.0961 0.0528 Wald ratio 1 trans NA
Non-cancer illness code self-reported: bladder problem (not cancer) -0.106 0.0562 0.0583 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension -0.0121 0.00663 0.0678 Wald ratio 1 trans NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.0536 0.0296 0.0703 Wald ratio 1 trans NA
Diagnoses - main ICD10: G47 Sleep disorders -0.1 0.0555 0.0713 Wald ratio 1 trans NA
Lung cancer -0.053 0.0296 0.0735 Wald ratio 1 trans NA
…and 98 more outcomes (see JSON)              

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

14 association rows across 6 traits (13 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 VEGFD levels (id: OID00468_OID20662) 9e-2227 rs192812042 1 GCST90859829 no MR -> candidate analysis
Circulating VEGFD levels (id: OID01319_OID20662) 2e-2062 rs192812042 1 GCST90860514 no MR -> candidate analysis
Pirin levels 5e-865 rs925653 1 GCST90249006 no MR -> candidate analysis
vascular endothelial growth factor D levels 1e-244 rs192812042 6 GCST90250162 no MR -> candidate analysis
Serum levels of protein VEGFD 2e-122 rs192812042 4 GCST90087372 no MR -> candidate analysis
ACE2 levels 9e-9 rs143380244 1 GCST90128424 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 250 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
COVID-19 0.534 common-variant locus no MR -> candidate analysis

Of the 1 rows above, 1 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 (Pirin)
gnomAD constraint pLI=1.2e-07, LOEUF=1.3 — LoF-tolerant
GWAS Catalog 16 unique SNPs / 32 rows
ClinVar 223 records; 8 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance