CausalSentinel

Protein Dossier — SEMG2 (Semenogelin-2)

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
Age at menarche -0.0621 0.0116 9.00e-08 Wald ratio 1 trans 0.88
Weight -0.0217 0.00414 1.55e-07 Wald ratio 1 trans 0.0065
Body mass index (BMI) -0.0184 0.00468 8.63e-05 Wald ratio 1 trans NA
Non-cancer illness code self-reported: osteoarthritis -0.0631 0.0167 1.57e-04 Wald ratio 1 trans NA
Ovarian cancer 0.092 0.026 3.95e-04 Wald ratio 1 trans NA
Serum cystatin C (eGFRcys) -0.0135 0.00383 4.25e-04 Wald ratio 1 trans NA
High grade serous ovarian cancer 0.0891 0.0309 0.00394 Wald ratio 1 trans NA
Small vessel disease 0.207 0.0727 0.00435 Wald ratio 1 trans NA
Total cholesterol -0.0294 0.0104 0.00473 Wald ratio 1 trans NA
Pulse rate -0.023 0.00827 0.00541 Wald ratio 1 trans NA
HDL cholesterol -0.0256 0.00968 0.00825 Wald ratio 1 trans NA
Creatinine (enzymatic) in urine -0.0114 0.00449 0.011 Wald ratio 1 trans NA
…and 84 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 7 traits (11 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
WFDC12 protein levels 1e-33 rs555590563 7 GCST90471073 no MR -> candidate analysis
Elafin levels 3e-21 rs34274189 2 GCST90162216 no MR -> candidate analysis
Height (baseline) 2e-15 rs11699099 1 GCST90565843 no MR -> candidate analysis
PI3 protein levels 1e-11 rs6017525 1 GCST90470230 no MR -> candidate analysis
Asthma 3e-6 rs16989837 1 GCST005212 MR: beta=-0.00917, p=0.489 (trans)
Bipolar disorder 3e-6 rs190905111 1 GCST008103 MR: beta=-0.0903, p=0.375 (trans)
Gut microbiota (bacterial taxa, hurdle binary method) 3e-6 rs6124695 1 GCST010396 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 45 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
nephrotic syndrome 0.041 common-variant locus no MR -> candidate analysis
sialolithiasis 0.041 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=0.41, LOEUF=0.962 — LoF-tolerant
GWAS Catalog 53 unique SNPs / 106 rows
ClinVar 104 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance