CausalSentinel

Protein Dossier — MUC16 (Mucin-16)

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: asthma 0.0565 0.0108 1.89e-07 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.0594 0.0159 1.86e-04 Wald ratio 1 trans NA
Diagnoses - main ICD10: R14 Flatulence and related conditions 0.355 0.121 0.00343 Wald ratio 1 trans NA
Clear cell ovarian cancer 0.222 0.0794 0.00518 Wald ratio 1 trans NA
Eye problems or disorders: Cataract -0.0665 0.0239 0.00543 Wald ratio 1 trans NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux 0.0504 0.0188 0.00723 Wald ratio 1 trans NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine 0.0699 0.0269 0.00933 Wald ratio 1 trans NA
Eczema 0.141 0.0676 0.0375 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertrophic cardiomyopathy (hcm or hocm) 0.41 0.2 0.0398 Wald ratio 1 trans NA
Cancer code self-reported: prostate cancer 0.0902 0.0439 0.04 Wald ratio 1 trans NA
Ovarian cancer 0.0536 0.0262 0.0412 Wald ratio 1 trans NA
Non-cancer illness code self-reported: depression 0.0332 0.0163 0.0424 Wald ratio 1 trans NA
…and 56 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

74 association rows across 69 traits (22 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
Mucin-16 levels 2e-36 rs61742668 1 GCST90248540 no MR -> candidate analysis
Breakthrough COVID-19 susceptibility after at least one dose 5e-34 rs11673136 1 GCST90448695 no MR -> candidate analysis
Circulating MUC16 levels (id: OID00741_OID21378) 5e-27 rs10421318 2 GCST90860082 no MR -> candidate analysis
Circulating MUC16 levels (id: OID05549_OID21378) 2e-23 rs10421318 2 GCST90860761 no MR -> candidate analysis
MUC16 protein levels 2e-23 rs10421318 2 GCST90469964 no MR -> candidate analysis
Asthma 6e-21 rs10416530 3 GCST90399687 MR: beta=0.0565, p=1.89e-07 (trans)
Serum cancer antigen 125 (CA 125) levels 2e-17 rs73005873 1 GCST009647 no MR -> candidate analysis
Ovarian cancer-related tumor marker CA 125 levels 1e-16 rs12976386 1 GCST90012078 no MR -> candidate analysis
Complex ventricular septal defect 3e-16 rs200791776 1 GCST90246230 no MR -> candidate analysis
Gut microbial network clusters (Salmon (at 1 year) x Househo 7e-11 rs12974378 1 GCST90569451 no MR -> candidate analysis
Gut microbial network clusters (Pink (at 1 year) x Winter Bi 9e-11 rs78342591 1 GCST90569460 no MR -> candidate analysis
Gut microbial network clusters (Salmon (at 1 year) x Househo 9e-10 rs12974378 1 GCST90569455 no MR -> candidate analysis
…and 57 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 898 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
alcohol drinking 0.696 common-variant locus no MR -> candidate analysis
asthma 0.603 common-variant locus MR: beta=0.0565, p=1.89e-07 (trans)
ovarian dysfunction 0.485 common-variant locus no MR -> candidate analysis
ventricular septal defect 0.481 common-variant locus no MR -> candidate analysis
COVID-19 0.403 common-variant locus no MR -> candidate analysis
response to COVID-19 vaccine 0.403 common-variant locus no MR -> candidate analysis
childhood onset asthma 0.37 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 6 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 4 known modulators (Mucin-16)
gnomAD constraint pLI=2.2e-155, LOEUF=0.81 — LoF-tolerant
GWAS Catalog 43 unique SNPs / 85 rows
ClinVar 719 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance