Protein Dossier — IL6ST (Interleukin-6 receptor 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 |
| Forced vital capacity (FVC) |
-0.0178 |
0.00562 |
0.00151 |
Inverse variance weighted |
4 |
cis |
NA |
| Forced vital capacity (FVC) |
-0.0178 |
0.00562 |
0.00151 |
Inverse variance weighted |
4 |
trans |
NA |
| Forced vital capacity (FVC) |
-0.0178 |
0.00562 |
0.00151 |
Inverse variance weighted |
4 |
trans |
NA |
| Forced vital capacity (FVC) |
-0.0178 |
0.00562 |
0.00151 |
Inverse variance weighted |
4 |
trans |
NA |
| Ferritin |
0.0887 |
0.0371 |
0.0169 |
Inverse variance weighted |
3 |
trans |
NA |
| Ferritin |
0.0887 |
0.0371 |
0.0169 |
Inverse variance weighted |
3 |
trans |
NA |
| Ferritin |
0.0887 |
0.0371 |
0.0169 |
Inverse variance weighted |
3 |
trans |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0138 |
0.00592 |
0.02 |
Inverse variance weighted |
4 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0138 |
0.00592 |
0.02 |
Inverse variance weighted |
4 |
trans |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0138 |
0.00592 |
0.02 |
Inverse variance weighted |
4 |
trans |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0138 |
0.00592 |
0.02 |
Inverse variance weighted |
4 |
trans |
NA |
| Ovarian cancer |
0.0851 |
0.0375 |
0.023 |
Inverse variance weighted |
4 |
cis |
NA |
| …and 361 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2620_4_2 |
gp130, soluble |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
44 association rows across 20 traits (32 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 |
| IL6ST protein levels |
2e-174 |
rs62363865 |
2 |
GCST90469603 |
no MR -> candidate analysis |
| Interleukin-6 receptor subunit beta levels |
5e-114 |
rs11739016 |
4 |
GCST90248077 |
no MR -> candidate analysis |
| IL31RA protein levels |
2e-63 |
rs13168372 |
6 |
GCST90469589 |
no MR -> candidate analysis |
| Height |
8e-30 |
rs1373998 |
3 |
GCST90245848 |
MR: beta=0.0144, p=0.364 (trans) |
| Serum levels of protein IL6ST |
1e-29 |
rs7726239 |
1 |
GCST90087986 |
no MR -> candidate analysis |
| Interleukin-6 receptor subunit beta levels (IL6ST.2620.4.2) |
1e-22 |
rs11574765 |
1 |
GCST90241649 |
no MR -> candidate analysis |
| Blood protein levels |
3e-20 |
rs10471960 |
1 |
GCST006585 |
no MR -> candidate analysis |
| Interleukin-6 receptor subunit beta level in Chronic kidney |
6e-14 |
rs13183065 |
1 |
GCST90237020 |
no MR -> candidate analysis |
| Height (baseline) |
7e-14 |
rs9791086 |
2 |
GCST90565843 |
no MR -> candidate analysis |
| IgG glycosylation |
7e-11 |
rs17348299 |
13 |
GCST001848 |
no MR -> candidate analysis |
| Body size or adipose distribution (multivariate analysis) |
3e-10 |
rs6870870 |
1 |
GCST90624105 |
no MR -> candidate analysis |
| Mean spheric corpuscular volume |
5e-10 |
rs199666144 |
1 |
GCST90002397 |
no MR -> candidate analysis |
| …and 8 more traits (see JSON) |
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4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 1738 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 |
| Autosomal recessive hyper-IgE syndrome |
0.824 |
— |
established (curated) |
no MR -> candidate analysis |
| Stuve-Wiedemann syndrome 2 |
0.763 |
— |
established (curated) |
no MR -> candidate analysis |
| hyper-IgE recurrent infection syndrome 4A, autosomal dominant |
0.779 |
— |
established (curated) |
no MR -> candidate analysis |
| immunodeficiency 94 with autoinflammation and dysmorphic facies |
0.698 |
— |
established (curated) |
no MR -> candidate analysis |
| Stuve-Wiedemann syndrome |
0.547 |
— |
established (curated) |
no MR -> candidate analysis |
| genetic developmental and epileptic encephalopathy |
0.509 |
— |
established (curated) |
no MR -> candidate analysis |
| alcohol drinking |
0.5 |
— |
common-variant locus |
no MR -> candidate analysis |
| stroke disorder |
0.45 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 8 rows above, 8 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 (Interleukin-6 receptor subunit beta) |
| gnomAD constraint |
pLI=1, LOEUF=0.37 — LoF-INTOLERANT |
| GWAS Catalog |
43 unique SNPs / 86 rows |
| ClinVar |
663 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1738 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘IL6ST’ and resolved to ‘Interleukin-6 receptor subunit beta’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 663 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 20 traits by best p-value, aggregated from 44 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/P40189 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000134352/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3124734/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/IL6ST — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/IL6ST — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=IL6ST%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/IL6ST — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:16:27 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none