Protein Dossier — POMC (Pro-opiomelanocortin)
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: high cholesterol |
-0.0734 |
0.0177 |
3.48e-05 |
Wald ratio |
1 |
trans |
NA |
| ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.102 |
0.0294 |
5.23e-04 |
Wald ratio |
1 |
trans |
NA |
| Hearing difficulty or problems: Yes |
-0.0317 |
0.0108 |
0.0035 |
Wald ratio |
1 |
trans |
NA |
| Cough on most days |
-0.0976 |
0.0343 |
0.00449 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: R14 Flatulence and related conditions |
0.463 |
0.165 |
0.00493 |
Wald ratio |
1 |
trans |
NA |
| Forced vital capacity (FVC) |
0.0137 |
0.005 |
0.00614 |
Wald ratio |
1 |
trans |
NA |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.0424 |
0.016 |
0.00793 |
Wald ratio |
1 |
trans |
NA |
| Forced expiratory volume in 1-second (FEV1) |
0.0133 |
0.00527 |
0.0113 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: mania or bipolar disorder or manic depression |
0.238 |
0.095 |
0.0121 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: ankylosing spondylitis |
0.205 |
0.0947 |
0.0302 |
Wald ratio |
1 |
trans |
NA |
| High grade serous ovarian cancer |
0.0871 |
0.0407 |
0.0322 |
Wald ratio |
1 |
trans |
NA |
| Sleep duration |
0.0101 |
0.00475 |
0.033 |
Wald ratio |
1 |
trans |
NA |
| …and 70 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2558_51_3 |
b-Endorphin |
Suhre K |
2019 |
prot-c-4890_10_1 |
ACTH |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
24 association rows across 18 traits (20 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 |
| POMC protein levels |
1e-29 |
rs3754861 |
1 |
GCST90470284 |
no MR -> candidate analysis |
| Weight |
5e-27 |
rs934778 |
2 |
GCST90662910 |
MR: beta=-0.0147, p=0.11 (trans) |
| Hair color |
3e-21 |
rs4665773 |
1 |
GCST007082 |
no MR -> candidate analysis |
| Body mass index |
4e-21 |
rs13388961 |
4 |
GCST90301650 |
no MR -> candidate analysis |
| Weight (UKB data field 21002) |
2e-20 |
rs934778 |
1 |
GCST90468183 |
no MR -> candidate analysis |
| Metabolic syndrome |
1e-19 |
rs934778 |
1 |
GCST90444487 |
no MR -> candidate analysis |
| Height (baseline) |
7e-17 |
rs34914018 |
2 |
GCST90565843 |
no MR -> candidate analysis |
| Height |
3e-16 |
rs7566506 |
1 |
GCST90245848 |
no MR -> candidate analysis |
| Uterine fibroids |
3e-15 |
rs12619264 |
2 |
GCST90461957 |
no MR -> candidate analysis |
| Hip circumference adjusted for BMI |
2e-12 |
rs12473543 |
1 |
GCST90020028 |
no MR -> candidate analysis |
| Red vs. brown/black hair color |
1e-10 |
rs76645364 |
1 |
GCST006986 |
no MR -> candidate analysis |
| Body mass index (MTAG) |
5e-9 |
rs3754861 |
1 |
GCST90179150 |
no MR -> candidate analysis |
| …and 6 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 1989 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 |
| obesity due to pro-opiomelanocortin deficiency |
0.827 |
— |
established (curated) |
no MR -> candidate analysis |
| Obesity |
0.739 |
— |
established (curated) |
no MR -> candidate analysis |
| obesity disorder |
0.08 |
— |
common-variant locus |
no MR -> candidate analysis |
| inherited obesity |
0.297 |
— |
established (curated) |
no MR -> candidate analysis |
| hereditary disease |
0.679 |
— |
established (curated) |
no MR -> candidate analysis |
| autoimmune disease |
0.618 |
— |
common-variant locus |
no MR -> candidate analysis |
| hair color |
0.613 |
— |
common-variant locus |
no MR -> candidate analysis |
| cardiovascular disorder |
0.51 |
— |
common-variant locus |
no MR -> candidate analysis |
| uterine corpus leiomyoma |
0.476 |
— |
common-variant locus |
no MR -> candidate analysis |
| hypertensive disorder |
0.457 |
— |
common-variant locus |
no MR -> candidate analysis |
| Crohn disease |
0.457 |
— |
common-variant locus |
no MR -> candidate analysis |
| ulcerative colitis |
0.456 |
— |
common-variant locus |
no MR -> candidate analysis |
| inflammatory spondylopathy |
0.463 |
— |
common-variant locus |
no MR -> candidate analysis |
| atrial fibrillation |
0.398 |
— |
common-variant locus |
no MR -> candidate analysis |
| mental disorder |
0.344 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 15 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=2.2e-07, LOEUF=1.51 — LoF-tolerant |
| GWAS Catalog |
101 unique SNPs / 210 rows |
| ClinVar |
250 records; 5 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1989 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 ‘POMC’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 250 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 18 of 18 traits by best p-value, aggregated from 24 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/P01189 — 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/ENSG00000115138/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/POMC — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/POMC — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=POMC%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/POMC — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:30:35 · 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: pharmgkb