CausalSentinel

Protein Dossier — GPC1 (Glypican-1)

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
Non-cancer illness code self-reported: pneumothorax 0.872 0.193 6.43e-06 Wald ratio 1 cis NA
Gallbladder cancer 2.94 0.892 9.89e-04 Wald ratio 1 cis NA
HOMA-IR 0.0519 0.0189 0.00596 Wald ratio 1 cis NA
HOMA-B 0.0401 0.0149 0.00697 Wald ratio 1 cis NA
Non-cancer illness code self-reported: sleep apnoea 0.298 0.123 0.0156 Wald ratio 1 cis NA
Alzheimer’s disease 0.145 0.067 0.0306 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension -0.0339 0.0159 0.0332 Wald ratio 1 cis NA
Diagnoses - main ICD10: R35 Polyuria 0.242 0.115 0.0359 Wald ratio 1 cis NA
Diagnoses - main ICD10: R14 Flatulence and related conditions 0.505 0.243 0.0378 Wald ratio 1 cis NA
Systemic lupus erythematosus 0.358 0.178 0.0439 Wald ratio 1 cis NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) 0.111 0.0575 0.0536 Wald ratio 1 cis NA
Fractured bone site(s): Other bones 0.0704 0.0366 0.0547 Wald ratio 1 cis NA
…and 89 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

59 association rows across 35 traits (43 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 GPC1 levels 5e-654 rs11892254 3 GCST90860018 no MR -> candidate analysis
Glypican-1 levels 1e-181 rs1126920 2 GCST90247755 no MR -> candidate analysis
GPC1 protein levels 6e-139 rs11892190 7 GCST90469386 no MR -> candidate analysis
Dual specificity phosphatase 28 levels 2e-72 rs148245427 1 GCST90247371 no MR -> candidate analysis
Height 1e-40 rs12467087 5 GCST90245848 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 2e-16 rs113438952 4 GCST90468087 no MR -> candidate analysis
Male-pattern baldness 2e-14 rs76710549 1 GCST007020 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 2e-14 rs6742784 1 GCST90838669 no MR -> candidate analysis
Cholelithiasis with acute cholecystitis (PheCode 574.11) 2e-12 rs557276480 1 GCST90480349 no MR -> candidate analysis
Infection with drug-resistant microorganisms (PheCode 41.9) 2e-11 rs191571179 1 GCST90479748 no MR -> candidate analysis
Balding type 1 5e-11 rs56003038 1 GCST007038 no MR -> candidate analysis
Keloid 6e-10 rs12989123 2 GCST90652487 no MR -> candidate analysis
…and 23 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 307 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
keloid 0.405 common-variant locus no MR -> candidate analysis
androgenetic alopecia 0.393 common-variant locus no MR -> candidate analysis
infectious disease 0.353 common-variant locus no MR -> candidate analysis
liver disorder 0.306 common-variant locus no MR -> candidate analysis
cholelithiasis 0.304 common-variant locus no MR -> candidate analysis

Of the 5 rows above, 5 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=0.0011, LOEUF=0.7 — LoF-tolerant
GWAS Catalog 71 unique SNPs / 129 rows
ClinVar 255 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance