Protein Dossier — IL12RB2 (Interleukin-12 receptor subunit beta-2)
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 |
| Non-cancer illness code self-reported: chronic obstructive airways disease or copd |
0.359 |
0.123 |
0.00352 |
Wald ratio |
1 |
cis |
NA |
| Ulcerative colitis |
0.146 |
0.0523 |
0.00526 |
Wald ratio |
1 |
cis |
NA |
| Inflammatory bowel disease |
0.114 |
0.0414 |
0.00569 |
Wald ratio |
1 |
cis |
NA |
| Hirschsprung’s disease |
-1.4 |
0.505 |
0.00572 |
Wald ratio |
1 |
cis |
NA |
| Urinary albumin-to-creatinine ratio |
-0.0623 |
0.0241 |
0.00986 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R55 Syncope and collapse |
0.202 |
0.0883 |
0.0219 |
Wald ratio |
1 |
cis |
NA |
| Cough on most days |
0.105 |
0.0466 |
0.0246 |
Wald ratio |
1 |
cis |
NA |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.0576 |
0.0261 |
0.0272 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.067 |
0.0312 |
0.0316 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: N81 Female genital prolapse |
-0.23 |
0.108 |
0.0326 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: C50 Malignant neoplasm of breast |
-0.204 |
0.0979 |
0.0372 |
Wald ratio |
1 |
cis |
NA |
| Age at menarche |
0.0506 |
0.0244 |
0.038 |
Wald ratio |
1 |
cis |
NA |
| …and 63 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3815_14_1 |
IL-12 RB2 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
60 association rows across 29 traits (49 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 |
| Primary biliary cholangitis |
5e-65 |
rs6679356 |
7 |
GCST90061442 |
no MR -> candidate analysis |
| Interleukin-12 receptor subunit beta-2 levels |
4e-49 |
rs7518266 |
4 |
GCST90425888 |
no MR -> candidate analysis |
| Primary biliary cirrhosis |
2e-38 |
rs72678531 |
2 |
GCST005581 |
no MR -> candidate analysis |
| Systemic lupus erythematosus (MTAG) |
8e-17 |
rs6679356 |
3 |
GCST90270940 |
no MR -> candidate analysis |
| Serum levels of protein IL12RB2 |
3e-16 |
rs12139687 |
1 |
GCST90088527 |
no MR -> candidate analysis |
| Hypothyroidism |
7e-14 |
rs72678531 |
3 |
GCST90627750 |
MR: beta=0.0479, p=0.264 (cis) |
| Autoimmune hypothyroidism |
8e-14 |
rs10489626 |
1 |
GCST90837324 |
no MR -> candidate analysis |
| Inflammatory skin disease |
6e-13 |
rs12119179 |
1 |
GCST002740 |
no MR -> candidate analysis |
| Crohn’s disease or systemic sclerosis |
1e-11 |
rs6659932 |
1 |
GCST010124 |
no MR -> candidate analysis |
| Tics and stuttering (PheCode 313.2) |
2e-11 |
rs192123185 |
1 |
GCST90480763 |
no MR -> candidate analysis |
| Behcet’s disease |
2e-11 |
rs1495965 |
3 |
GCST000728 |
no MR -> candidate analysis |
| ICD10 K50, K51: inflammatory bowel disease |
5e-11 |
rs10889680 |
2 |
GCST90432147 |
no MR -> candidate analysis |
| …and 17 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 311 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 |
| primary biliary cholangitis |
0.743 |
— |
common-variant locus |
no MR -> candidate analysis |
| rheumatoid arthritis |
0.752 |
— |
common-variant locus |
no MR -> candidate analysis |
| hypothyroidism |
0.743 |
— |
common-variant locus |
MR: beta=0.0479, p=0.264 (cis) |
| systemic lupus erythematosus |
0.686 |
— |
common-variant locus |
no MR -> candidate analysis |
| Crohn disease |
0.686 |
— |
common-variant locus |
no MR -> candidate analysis |
| systemic sclerosis |
0.663 |
— |
common-variant locus |
no MR -> candidate analysis |
| biliary liver cirrhosis |
0.658 |
— |
common-variant locus |
no MR -> candidate analysis |
| Behcet disease |
0.589 |
— |
common-variant locus |
no MR -> candidate analysis |
| enteritis |
0.527 |
— |
common-variant locus |
no MR -> candidate analysis |
| myositis disease |
0.493 |
— |
common-variant locus |
no MR -> candidate analysis |
| Hashimoto thyroiditis |
0.49 |
— |
common-variant locus |
no MR -> candidate analysis |
| ulcerative colitis |
0.487 |
— |
common-variant locus |
MR: beta=0.146, p=0.00526 (cis) |
| retinal degeneration |
0.47 |
— |
common-variant locus |
no MR -> candidate analysis |
| psoriasis |
0.456 |
— |
common-variant locus |
no MR -> candidate analysis |
| Tics |
0.462 |
— |
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=6.8e-26, LOEUF=1.1 — LoF-tolerant |
| GWAS Catalog |
77 unique SNPs / 154 rows |
| ClinVar |
714 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 311 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — No ChEMBL target for ‘IL12RB2’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 714 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 29 traits by best p-value, aggregated from 60 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/Q99665 — 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/ENSG00000081985/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/IL12RB2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/IL12RB2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=IL12RB2%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/IL12RB2 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:11:06 · 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