CausalSentinel

Protein Dossier — MCAM (Cell surface glycoprotein MUC18)

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
Serum creatinine (eGFRcrea) -0.0292 0.00694 2.67e-05 Wald ratio 1 cis NA
Platelet count -12.4 3.41 2.87e-04 Wald ratio 1 cis NA
Height -0.0764 0.0236 0.00122 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma 0.146 0.0463 0.0016 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis 0.378 0.125 0.00258 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0882 0.0298 0.00307 Wald ratio 1 cis NA
Chronic kidney disease 0.312 0.118 0.00812 Wald ratio 1 cis NA
Coronary heart disease -0.203 0.077 0.00857 Wald ratio 1 cis NA
Transferrin -0.213 0.0819 0.00928 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux 0.185 0.0769 0.016 Wald ratio 1 cis NA
Non-cancer illness code self-reported: anxiety or panic attacks 0.287 0.126 0.0227 Wald ratio 1 cis NA
Years of schooling -0.0625 0.0278 0.0244 Wald ratio 1 cis NA
…and 92 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

15 association rows across 14 traits (15 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
ITGB1/MCAM protein level ratio 2e-165 rs34587557 1 GCST90315226 no MR -> candidate analysis
CD58/MCAM protein level ratio 1e-145 rs34587557 1 GCST90313852 no MR -> candidate analysis
MCAM/NTRK3 protein level ratio 4e-143 rs34587557 1 GCST90315409 no MR -> candidate analysis
MCAM/NCAM1 protein level ratio 6e-124 rs34587557 1 GCST90315408 no MR -> candidate analysis
MCAM protein levels 5e-123 rs34587557 1 GCST90469870 no MR -> candidate analysis
Plateletcrit 1e-27 rs35929108 1 GCST90002400 no MR -> candidate analysis
Height 1e-27 rs2511847 1 GCST90245848 MR: beta=-0.0764, p=0.00122 (cis)
Platelet count 1e-19 rs7944487 2 GCST90056183 MR: beta=-12.4, p=2.87e-04 (cis)
Platelet-to-lymphocyte ratio 2e-18 rs2511842 1 GCST90056184 no MR -> candidate analysis
Blood protein levels 6e-18 rs2511847 1 GCST006585 no MR -> candidate analysis
Platelet crit (UKB data field 30090) 5e-13 rs182494271 1 GCST90468096 no MR -> candidate analysis
High density lipoprotein cholesterol levels 1e-10 rs71484135 1 GCST90019510 no MR -> candidate analysis
…and 2 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 542 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
CBL-related disorder 0.195 established (curated) no MR -> candidate analysis
spinal fracture 0.136 common-variant locus no MR -> candidate analysis

Of the 2 rows above, 2 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 (Cell surface glycoprotein MUC18)
gnomAD constraint pLI=3.6e-13, LOEUF=0.87 — LoF-tolerant
GWAS Catalog 83 unique SNPs / 164 rows
ClinVar 165 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance