Protein Dossier — IGFBP3 (Insulin-like growth factor-binding protein 3)
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 |
| Diastolic blood pressure automated reading |
0.0366 |
0.00636 |
8.67e-09 |
Wald ratio |
1 |
cis |
NA |
| Systolic blood pressure automated reading |
-0.0316 |
0.00636 |
6.69e-07 |
Wald ratio |
1 |
cis |
NA |
| Height |
-0.028 |
0.00794 |
4.16e-04 |
Wald ratio |
1 |
cis |
NA |
| Squamous cell lung cancer |
-0.198 |
0.0663 |
0.00285 |
Wald ratio |
1 |
cis |
NA |
| Potassium in urine |
-0.0172 |
0.00631 |
0.00638 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: asthma |
0.0431 |
0.0167 |
0.00979 |
Wald ratio |
1 |
cis |
NA |
| Forced vital capacity (FVC) |
-0.0131 |
0.0051 |
0.00994 |
Wald ratio |
1 |
cis |
NA |
| Creatinine (enzymatic) in urine |
-0.015 |
0.00595 |
0.0118 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0134 |
0.00538 |
0.0128 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: small intestine or small bowel cancer |
0.472 |
0.191 |
0.0136 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: chronic obstructive airways disease or copd |
-0.395 |
0.163 |
0.0156 |
Wald ratio |
1 |
cis |
NA |
| Ischemic stroke |
-0.101 |
0.0435 |
0.0202 |
Wald ratio |
1 |
cis |
NA |
| …and 108 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2571_12_3 |
IGFBP-3 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
169 association rows across 71 traits (155 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 IGFBP3 levels |
3e-1029 |
rs2854744 |
2 |
GCST90860453 |
no MR -> candidate analysis |
| IGF-1 and IGFBP-3 levels (bivariate analysis) |
3e-195 |
rs11977526 |
1 |
GCST90102625 |
no MR -> candidate analysis |
| Serum levels of protein IGFALS |
2e-189 |
rs2854746 |
1 |
GCST90089525 |
no MR -> candidate analysis |
| Nutritionally-regulated adipose and cardiac enriched protein |
1e-182 |
rs2854746 |
1 |
GCST90248727 |
no MR -> candidate analysis |
| Serum levels of protein IGFBP3 |
4e-161 |
rs11977526 |
4 |
GCST90102624 |
no MR -> candidate analysis |
| Pulse pressure |
5e-139 |
rs11977526 |
27 |
GCST90310296 |
no MR -> candidate analysis |
| Insulin-like growth factor-binding protein 3 levels |
1e-116 |
rs145188037 |
6 |
GCST90248011 |
no MR -> candidate analysis |
| IGF 1 (UKB data field 30770) |
1e-104 |
rs2854746 |
3 |
GCST90468078 |
no MR -> candidate analysis |
| Insulin-like growth factors |
3e-101 |
rs11977526 |
1 |
GCST000937 |
no MR -> candidate analysis |
| IGFBP3 protein levels |
7e-59 |
rs1722116 |
8 |
GCST90469529 |
no MR -> candidate analysis |
| Height |
1e-49 |
rs6953668 |
11 |
GCST90245848 |
MR: beta=-0.028, p=4.16e-04 (cis) |
| IGF2 protein levels |
2e-49 |
rs2854746 |
3 |
GCST90453055 |
no MR -> candidate analysis |
| …and 59 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 1530 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 |
| Abnormality of the skeletal system |
0.786 |
— |
common-variant locus |
no MR -> candidate analysis |
| lymphatic system disorder |
0.594 |
— |
common-variant locus |
no MR -> candidate analysis |
| cataract |
0.575 |
— |
common-variant locus |
MR: beta=-0.168, p=0.047 (cis) |
| open-angle glaucoma |
0.563 |
— |
common-variant locus |
no MR -> candidate analysis |
| Alzheimer disease |
0.52 |
— |
common-variant locus |
no MR -> candidate analysis |
| prostate cancer |
0.526 |
— |
common-variant locus |
no MR -> candidate analysis |
| colorectal cancer |
0.526 |
— |
common-variant locus |
no MR -> candidate analysis |
| cancer |
0.512 |
— |
common-variant locus |
MR: beta=-0.198, p=0.00285 (cis) |
| hypertensive disorder |
0.506 |
— |
common-variant locus |
no MR -> candidate analysis |
| heart disorder |
0.522 |
— |
common-variant locus |
no MR -> candidate analysis |
| tenosynovitis |
0.486 |
— |
common-variant locus |
no MR -> candidate analysis |
| hypospadias |
0.468 |
— |
common-variant locus |
no MR -> candidate analysis |
| senile cataract |
0.46 |
— |
common-variant locus |
MR: beta=-0.168, p=0.047 (cis) |
| Age-related cataract |
0.453 |
— |
common-variant locus |
no MR -> candidate analysis |
| Back pain |
0.448 |
— |
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 (Insulin-like growth factor-binding protein 3) |
| gnomAD constraint |
pLI=0.93, LOEUF=0.549 — LoF-INTOLERANT |
| GWAS Catalog |
94 unique SNPs / 187 rows |
| ClinVar |
68 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
1 clinical annotations across 1 drugs |
phenome — Top 30 of 1530 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 ‘IGFBP3’ and resolved to ‘Insulin-like growth factor-binding protein 3’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 68 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 71 traits by best p-value, aggregated from 169 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/P17936 — 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/ENSG00000146674/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3997/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/IGFBP3 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/IGFBP3 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=IGFBP3%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=IGFBP3 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/IGFBP3 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:08:38 · 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