CausalSentinel

Protein Dossier — EBI3 (Interleukin-27 subunit beta)

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
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.0575 0.0195 0.00315 Wald ratio 1 cis NA
Non-cancer illness code self-reported: chronic obstructive airways disease or copd -0.124 0.0493 0.012 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine -0.0368 0.0152 0.0155 Wald ratio 1 cis NA
Fractured bone site(s): Arm 0.0564 0.0241 0.0194 Wald ratio 1 cis NA
Cough on most days -0.0308 0.0134 0.0214 Wald ratio 1 cis NA
Forearm bone mineral density 0.0362 0.0162 0.026 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt -0.0646 0.03 0.0314 Wald ratio 1 cis NA
Thyroid cancer -0.176 0.0833 0.0345 Wald ratio 1 cis NA
2hr glucose 0.0419 0.02 0.0361 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vitiligo 0.247 0.122 0.0433 Wald ratio 1 cis NA
Cigarettes smoked per day 0.162 0.0862 0.0605 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.0524 0.0287 0.0674 Wald ratio 1 cis NA
…and 104 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

24 association rows across 13 traits (24 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
Circulating EBI3_IL27 levels 1e-1975 rs4905 5 GCST90859764 no MR -> candidate analysis
Interleukin-27 subunit beta levels 3e-1862 rs353705 2 GCST90248066 no MR -> candidate analysis
Interleukin-27 levels 6e-1169 rs4905 4 GCST90012017 no MR -> candidate analysis
Interleukin-35 levels 2e-222 rs4740 1 GCST90423778 no MR -> candidate analysis
Interleukin-35 level in Chronic kidney disease with hyperten 8e-163 rs4740 1 GCST90235456 no MR -> candidate analysis
Interleukin-27 subunit beta level in Chronic kidney disease 1e-152 rs4740 1 GCST90233006 no MR -> candidate analysis
Blood protein levels in cardiovascular risk 5e-119 rs4905 1 GCST009731 no MR -> candidate analysis
IL-27 levels in early pregnancy 2e-94 rs4905 1 GCST90809109 no MR -> candidate analysis
HemK methyltransferase family member 2 levels 4e-64 rs4740 2 GCST90161266 no MR -> candidate analysis
IL27B protein level (protein group normalized intensity) 1e-63 rs4740 1 GCST90570739 no MR -> candidate analysis
Calbindin protein levels (SomaScan ID:20533-39) 2e-29 rs353705 1 GCST90438930 no MR -> candidate analysis
YJU2 protein levels 2e-16 rs694443 1 GCST90471089 no MR -> candidate analysis
…and 1 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 271 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
immune system disorder 0.271 common-variant locus no MR -> candidate analysis
gangrene 0.253 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 0 known modulators (Sequestosome-1)
gnomAD constraint pLI=1.2e-06, LOEUF=1.31 — LoF-tolerant
GWAS Catalog 70 unique SNPs / 140 rows
ClinVar 77 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance