Protein Dossier — IL12B (Interleukin-12 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 |
| Inflammatory bowel disease |
0.418 |
0.0345 |
9.59e-34 |
Wald ratio |
1 |
cis |
1.41e-12 |
| Crohn’s disease |
0.44 |
0.0419 |
7.95e-26 |
Wald ratio |
1 |
cis |
7.34e-12 |
| Ulcerative colitis |
0.365 |
0.0435 |
4.56e-17 |
Wald ratio |
1 |
cis |
3.23e-07 |
| Non-cancer illness code self-reported: psoriasis |
-0.00555 |
0.000892 |
5.10e-10 |
Wald ratio |
1 |
cis |
0.989 |
| High grade serous ovarian cancer |
0.229 |
0.0863 |
0.00794 |
Wald ratio |
1 |
trans |
NA |
| Ovarian cancer |
0.188 |
0.0727 |
0.00958 |
Wald ratio |
1 |
trans |
NA |
| Height |
0.0253 |
0.0102 |
0.0136 |
Wald ratio |
1 |
cis |
NA |
| Internalizing problems |
0.174 |
0.0765 |
0.0228 |
Wald ratio |
1 |
cis |
NA |
| Caudate volume |
-36.5 |
16.8 |
0.0294 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Arm |
-0.00177 |
0.00084 |
0.0352 |
Wald ratio |
1 |
cis |
NA |
| Squamous cell lung cancer |
0.188 |
0.0893 |
0.0358 |
Wald ratio |
1 |
cis |
NA |
| Alcohol intake frequency |
0.024 |
0.0122 |
0.0491 |
Wald ratio |
1 |
cis |
NA |
| …and 90 more outcomes (see JSON) |
|
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|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4494_63_2 |
IL-23 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
258 association rows across 107 traits (215 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 IL12B levels (id: OID00523_OID20666) |
3e-2108 |
rs4244437 |
3 |
GCST90859879 |
no MR -> candidate analysis |
| Circulating IL12B levels (id: OID00368_OID20666) |
4e-1702 |
rs4244437 |
3 |
GCST90859730 |
no MR -> candidate analysis |
| CD83/IL12A_IL12B protein level ratio |
5e-1617 |
rs6556416 |
1 |
GCST90313905 |
no MR -> candidate analysis |
| CD38/IL12A_IL12B protein level ratio |
2e-1488 |
rs6556416 |
1 |
GCST90313808 |
no MR -> candidate analysis |
| Circulating IL12A_IL12B levels |
2e-1474 |
rs4244437 |
3 |
GCST90860167 |
no MR -> candidate analysis |
| CD302/IL12A_IL12B protein level ratio |
2e-1406 |
rs6556416 |
1 |
GCST90313806 |
no MR -> candidate analysis |
| GZMA/IL12A_IL12B protein level ratio |
1e-1400 |
rs6556416 |
1 |
GCST90315009 |
no MR -> candidate analysis |
| IL12A_IL12B/LAG3 protein level ratio |
8e-1395 |
rs6556416 |
1 |
GCST90315147 |
no MR -> candidate analysis |
| BSG/IL12A_IL12B protein level ratio |
1e-1369 |
rs6556416 |
1 |
GCST90313532 |
no MR -> candidate analysis |
| GFRA2/IL12A_IL12B protein level ratio |
2e-1367 |
rs6556416 |
1 |
GCST90314925 |
no MR -> candidate analysis |
| Interleukin-12 subunit beta levels |
1e-361 |
rs10076557 |
4 |
GCST90274798 |
no MR -> candidate analysis |
| Bone mineral density mean |
1e-300 |
rs12513881 |
1 |
GCST90321120 |
no MR -> candidate analysis |
| …and 95 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 513 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 |
| psoriasis |
0.967 |
— |
common-variant locus |
MR: beta=-0.00555, p=5.10e-10 (cis) |
| Crohn disease |
0.921 |
— |
common-variant locus |
no MR -> candidate analysis |
| psoriasis vulgaris |
0.928 |
— |
common-variant locus |
no MR -> candidate analysis |
| psoriatic arthritis |
0.901 |
— |
common-variant locus |
no MR -> candidate analysis |
| ulcerative colitis |
0.883 |
— |
common-variant locus |
MR: beta=0.365, p=4.56e-17 (cis) |
| inflammatory bowel disease |
0.887 |
— |
common-variant locus |
MR: beta=0.418, p=9.59e-34 (cis) |
| skin disorder |
0.893 |
— |
common-variant locus |
no MR -> candidate analysis |
| seborrheic dermatitis |
0.849 |
— |
common-variant locus |
no MR -> candidate analysis |
| erythematosquamous dermatosis |
0.814 |
— |
common-variant locus |
no MR -> candidate analysis |
| Oral ulcer |
0.749 |
— |
common-variant locus |
no MR -> candidate analysis |
| type 2 diabetes mellitus |
0.757 |
— |
common-variant locus |
no MR -> candidate analysis |
| Takayasu arteritis |
0.598 |
— |
common-variant locus |
no MR -> candidate analysis |
| systemic lupus erythematosus |
0.601 |
— |
common-variant locus |
no MR -> candidate analysis |
| multiple sclerosis |
0.592 |
— |
common-variant locus |
no MR -> candidate analysis |
| primary biliary cholangitis |
0.593 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 12 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-12 subunit beta) |
| gnomAD constraint |
pLI=6.6e-07, LOEUF=0.949 — LoF-tolerant |
| GWAS Catalog |
172 unique SNPs / 424 rows |
| ClinVar |
271 records; 5 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
2 clinical annotations across 2 drugs |
phenome — Top 30 of 513 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 ‘IL12B’ and resolved to ‘Interleukin-12 subunit beta’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 271 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 107 traits by best p-value, aggregated from 258 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/P29460 — 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/ENSG00000113302/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3580484/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/IL12B — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/IL12B — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=IL12B%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=IL12B — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/IL12B — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:10:30 · 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