CausalSentinel

Protein Dossier — SEMA3C (Semaphorin-3C)

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
Systolic blood pressure automated reading 0.043 0.0143 0.00272 Wald ratio 1 cis NA
Height 0.0497 0.0171 0.00373 Wald ratio 1 cis NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.242 0.0868 0.00525 Wald ratio 1 cis NA
Cancer code self-reported: prostate cancer 0.323 0.121 0.00767 Wald ratio 1 cis NA
Diagnoses - main ICD10: J33 Nasal polyp 0.37 0.144 0.0104 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0464 0.0182 0.0107 Wald ratio 1 cis NA
Coronary heart disease 0.13 0.0534 0.0151 Wald ratio 1 cis NA
Type 2 diabetes 0.169 0.0711 0.0176 Wald ratio 1 cis NA
Total cholesterol -0.0691 0.0291 0.0177 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0522 0.023 0.0231 Wald ratio 1 cis NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate 0.296 0.131 0.0236 Wald ratio 1 cis NA
Serum cystatin C (eGFRcys) 0.0234 0.0109 0.0309 Wald ratio 1 cis NA
…and 88 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

174 association rows across 101 traits (131 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
Bone mineral density mean 2e-161 rs78465953 3 GCST90321120 no MR -> candidate analysis
Platelet glycoprotein 4 levels 2e-146 rs139906208 3 GCST90137913 no MR -> candidate analysis
HDL cholesterol levels x alcohol consumption (regular vs non 6e-51 rs4470970 3 GCST008075 no MR -> candidate analysis
mean corpuscular volume (MCV, mean, inv-norm transformed) 4e-34 rs7797401 2 GCST90475470 no MR -> candidate analysis
CD36 protein levels 1e-32 rs11980784 2 GCST90468627 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 3e-32 rs139906208 3 GCST90838667 no MR -> candidate analysis
mean corpuscular volume (MCV, minimum, inv-norm transformed) 5e-29 rs7797401 2 GCST90475474 no MR -> candidate analysis
Mean sphered cell volume (UKB data field 30270) 3e-28 rs181616813 1 GCST90468089 no MR -> candidate analysis
Semaphorin-3C levels 2e-26 rs7783868 2 GCST90249485 no MR -> candidate analysis
HDL x low social support interaction (2df test) 9e-23 rs139906208 2 GCST90570699 no MR -> candidate analysis
Red blood cell count 2e-22 rs148083940 5 GCST90002367 no MR -> candidate analysis
Red cell distribution width 6e-22 rs7797401 6 GCST004621 no MR -> candidate analysis
…and 89 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 501 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
atrial fibrillation 0.821 common-variant locus MR: beta=-0.211, p=0.215 (cis)
coronary artery disorder 0.726 common-variant locus no MR -> candidate analysis
glaucoma 0.703 common-variant locus MR: beta=-0.161, p=0.253 (cis)
open-angle glaucoma 0.686 common-variant locus no MR -> candidate analysis
ovarian dysfunction 0.64 common-variant locus no MR -> candidate analysis
inborn disorder of amino acid metabolism 0.523 common-variant locus no MR -> candidate analysis
atrial septal defect 0.448 common-variant locus no MR -> candidate analysis
subarachnoid hemorrhage 0.467 common-variant locus no MR -> candidate analysis
alopecia areata 0.459 common-variant locus no MR -> candidate analysis
posterior cortical atrophy 0.421 common-variant locus no MR -> candidate analysis
disorder of ear 0.431 common-variant locus no MR -> candidate analysis
glomerulonephritis 0.427 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.427 common-variant locus no MR -> candidate analysis
Alzheimer disease 0.421 common-variant locus no MR -> candidate analysis
shoulder fracture 0.405 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 13 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-06, LOEUF=0.67 — LoF-tolerant
GWAS Catalog 155 unique SNPs / 326 rows
ClinVar 289 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance