Protein Dossier — IGFBP5 (Insulin-like growth factor-binding protein 5)
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: kidney stone or ureter stone or bladder stone |
0.522 |
0.145 |
3.16e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: joint disorder |
0.481 |
0.2 |
0.0161 |
Wald ratio |
1 |
cis |
NA |
| Sleep duration |
-0.0384 |
0.0165 |
0.0198 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K20 Oesophagitis |
0.357 |
0.153 |
0.02 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Other bones |
-0.244 |
0.119 |
0.0405 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: C61 Malignant neoplasm of prostate |
0.367 |
0.187 |
0.0496 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: osteoporosis |
0.249 |
0.135 |
0.0647 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: G56 Mononeuropathies of upper limb |
-0.815 |
0.453 |
0.0716 |
Wald ratio |
1 |
cis |
NA |
| Eczema |
0.277 |
0.162 |
0.0863 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Ankle |
0.242 |
0.145 |
0.0959 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Wrist |
0.192 |
0.127 |
0.131 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: H25 Senile cataract |
0.282 |
0.189 |
0.137 |
Wald ratio |
1 |
cis |
NA |
| …and 42 more outcomes (see JSON) |
|
|
|
|
|
|
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2685_21_2 |
IGFBP-5 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
9 association rows across 9 traits (5 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 |
| Serum levels of protein IGFBP5 |
2e-48 |
rs11575194 |
1 |
GCST90088017 |
no MR -> candidate analysis |
| Height |
2e-24 |
rs11575134 |
1 |
GCST90245848 |
no MR -> candidate analysis |
| Oxysterol-binding protein-related protein 11 levels (OSBPL11 |
9e-12 |
rs11575194 |
1 |
GCST90242184 |
no MR -> candidate analysis |
| Pulse pressure |
4e-10 |
rs11575194 |
1 |
GCST90310296 |
no MR -> candidate analysis |
| Glycated hemoglobin levels |
2e-9 |
rs10932672 |
1 |
GCST90134495 |
no MR -> candidate analysis |
| Visceral fat |
1e-7 |
rs2241193 |
1 |
GCST001525 |
no MR -> candidate analysis |
| Metabolite levels |
5e-6 |
rs9341226 |
1 |
GCST009391 |
no MR -> candidate analysis |
| Systolic blood pressure |
7e-6 |
rs11575194 |
1 |
GCST90310294 |
MR: beta=0.0179, p=0.407 (cis) |
| Behenoyl dihydrosphingomyelin (d18:0/22:0) levels |
9e-6 |
rs2067039 |
1 |
GCST90503964 |
no MR -> candidate analysis |
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 426 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 |
| hypothyroidism |
0.534 |
— |
common-variant locus |
MR: beta=0.096, p=0.264 (cis) |
| nodular goiter |
0.479 |
— |
common-variant locus |
no MR -> candidate analysis |
| Incisional hernia |
0.465 |
— |
common-variant locus |
no MR -> candidate analysis |
| hyperthyroidism |
0.447 |
— |
common-variant locus |
MR: beta=-0.432, p=0.372 (cis) |
| thyrotoxicosis |
0.432 |
— |
common-variant locus |
MR: beta=-0.432, p=0.372 (cis) |
| thyroid gland disorder |
0.398 |
— |
common-variant locus |
no MR -> candidate analysis |
| cervical carcinoma |
0.372 |
— |
common-variant locus |
no MR -> candidate analysis |
| nontoxic goiter |
0.365 |
— |
common-variant locus |
no MR -> candidate analysis |
| coronary atherosclerosis |
0.308 |
— |
common-variant locus |
no MR -> candidate analysis |
| Hashimoto thyroiditis |
0.307 |
— |
common-variant locus |
no MR -> candidate analysis |
| autoimmune disease |
0.296 |
— |
common-variant locus |
no MR -> candidate analysis |
| multinodular goiter |
0.28 |
— |
common-variant locus |
no MR -> candidate analysis |
| Age-related cataract |
0.262 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.164 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 14 rows above, 11 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 5) |
| gnomAD constraint |
pLI=0.2, LOEUF=0.694 — LoF-tolerant |
| GWAS Catalog |
61 unique SNPs / 122 rows |
| ClinVar |
83 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 426 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 ‘IGFBP5’ and resolved to ‘Insulin-like growth factor-binding protein 5’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 83 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 9 of 9 traits by best p-value, aggregated from 9 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/P24593 — 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/ENSG00000115461/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2665/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/IGFBP5 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/IGFBP5 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=IGFBP5%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/IGFBP5 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:08:53 · 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