CausalSentinel

Protein Dossier — SOCS3 (Suppressor of cytokine signaling 3)

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
Forced vital capacity (FVC) 0.0156 0.00328 1.85e-06 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) 0.013 0.00346 1.71e-04 Wald ratio 1 trans NA
Non-cancer illness code self-reported: high cholesterol 0.0322 0.0105 0.00211 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension 0.0181 0.00669 0.0067 Wald ratio 1 trans NA
Neuroblastoma 0.186 0.0712 0.00879 Wald ratio 1 trans NA
Neo-extraversion -0.349 0.134 0.00894 Wald ratio 1 trans NA
Non-cancer illness code self-reported: migraine -0.0635 0.0246 0.00991 Wald ratio 1 trans NA
Age at menarche -0.024 0.00932 0.01 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.0416 0.017 0.0147 Wald ratio 1 trans NA
Non-cancer illness code self-reported: arthritis (nos) -0.123 0.0522 0.0183 Wald ratio 1 trans NA
Schizophrenia -0.0401 0.0171 0.0187 Wald ratio 1 trans NA
Fractured bone site(s): Ankle 0.0737 0.0317 0.02 Wald ratio 1 trans 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

57 association rows across 36 traits (50 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
C-reactive protein levels (UKB data field 30710) 4e-38 rs11658216 3 GCST90468064 no MR -> candidate analysis
C-reactive protein levels 3e-36 rs6501207 6 GCST009777 no MR -> candidate analysis
C-reactive protein 1e-30 rs12952093 1 GCST90018950 no MR -> candidate analysis
C-reactive protein levels (MTAG) 2e-27 rs6501207 6 GCST90179146 no MR -> candidate analysis
Height 1e-26 rs7213427 3 GCST90245848 MR: beta=0.00709, p=0.14 (trans)
Platelet count 7e-19 rs9892622 3 GCST90662907 no MR -> candidate analysis
Aspartate aminotransferase (AST, mean, inv-norm transformed) 5e-18 rs4969172 2 GCST90475121 no MR -> candidate analysis
Heel bone mineral density 1e-17 rs7225449 1 GCST007066 MR: beta=-0.00632, p=0.222 (trans)
Aspartate aminotransferase (AST, minimum, inv-norm transform 5e-17 rs6501201 2 GCST90475124 no MR -> candidate analysis
Glycated haemoglobin HbA1c levels (UKB data field 30750) 7e-17 rs9892622 1 GCST90468072 no MR -> candidate analysis
Creatine kinase levels 1e-16 rs6501201 2 GCST90838680 no MR -> candidate analysis
Platelet count (UKB data field 30080) 1e-14 rs11077357 1 GCST90468095 no MR -> candidate analysis
…and 24 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 820 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
asthma 0.269 common-variant locus MR: beta=0.00883, p=0.426 (trans)
respiratory system disorder 0.215 common-variant locus no MR -> candidate analysis
osteoarthritis 0.186 common-variant locus MR: beta=-0.0471, p=0.285 (trans)
open-angle glaucoma 0.19 common-variant locus no MR -> candidate analysis

Of the 4 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=0.27, LOEUF=0.901 — LoF-tolerant
GWAS Catalog 115 unique SNPs / 276 rows
ClinVar 52 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance