CausalSentinel

Protein Dossier — SEMA3G (Semaphorin-3G)

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
HDL cholesterol 0.0845 0.0182 3.61e-06 Wald ratio 1 cis NA
Triglycerides -0.0689 0.0175 8.28e-05 Wald ratio 1 cis NA
Age at menarche 0.093 0.0296 0.0017 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] -0.373 0.123 0.00246 Wald ratio 1 cis NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis 0.226 0.0804 0.00483 Wald ratio 1 cis NA
Height 0.0409 0.0149 0.00596 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb -0.341 0.126 0.00687 Wald ratio 1 cis NA
Body mass index (BMI) -0.0309 0.0116 0.00746 Wald ratio 1 cis NA
Lung cancer -0.191 0.0849 0.0246 Wald ratio 1 cis NA
Non-cancer illness code self-reported: uterine fibroids -0.279 0.126 0.0267 Wald ratio 1 cis NA
Diagnoses - main ICD10: I30 Acute pericarditis 0.774 0.349 0.0268 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis -0.0938 0.0426 0.0275 Wald ratio 1 cis NA
…and 107 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 11 traits (14 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
Semaphorin-3G levels 4e-107 rs2016575 2 GCST90249487 no MR -> candidate analysis
Serum levels of protein SEMA3G 9e-20 rs13091025 1 GCST90089104 no MR -> candidate analysis
Apolipoprotein A levels (UKB data field 30630) 6e-18 rs82825 1 GCST90468061 no MR -> candidate analysis
Semaphorin-3G levels (SEMA3G.5628.21.3) 2e-17 rs2016575 1 GCST90242746 no MR -> candidate analysis
Metabolic syndrome 2e-14 rs2016575 2 GCST90444487 no MR -> candidate analysis
Waist circumference adjusted for body mass index 7e-14 rs62257614 2 GCST009867 no MR -> candidate analysis
Calcium levels 1e-10 rs648514 1 GCST90018951 no MR -> candidate analysis
Cholesteryl Esters to Total Lipids in Very Large HDL percent 1e-10 rs82825 1 GCST90501297 no MR -> candidate analysis
Intelligence 4e-9 rs648514 1 GCST90264174 no MR -> candidate analysis
Waist-to-hip ratio adjusted for BMI 4e-9 rs62257614 1 GCST009858 no MR -> candidate analysis
Fluid intelligence score (baseline) 2e-8 rs661777 1 GCST90565842 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 129 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
diverticular disease 0.446 common-variant locus MR: beta=-0.191, p=0.0552 (cis)
hypertrophic cardiomyopathy 0.271 common-variant locus no MR -> candidate analysis
gastroesophageal reflux disease 0.21 common-variant locus no MR -> candidate analysis
esophageal disorder 0.188 common-variant locus no MR -> candidate analysis

Of the 4 rows above, 3 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=1.1e-19, LOEUF=0.991 — LoF-tolerant
GWAS Catalog 104 unique SNPs / 260 rows
ClinVar 408 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance