Protein Dossier — HBEGF (Proheparin-binding EGF-like growth factor)
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 |
| Mean platelet volume |
-0.0759 |
0.00592 |
1.30e-37 |
Wald ratio |
1 |
trans |
NA |
| Platelet count |
20.4 |
2.17 |
4.86e-21 |
Wald ratio |
1 |
trans |
0.991 |
| Triglycerides |
-0.152 |
0.0253 |
1.73e-09 |
Wald ratio |
1 |
trans |
0.85 |
| HDL cholesterol |
0.125 |
0.0258 |
1.21e-06 |
Wald ratio |
1 |
trans |
NA |
| Years of schooling |
0.0861 |
0.0215 |
6.33e-05 |
Wald ratio |
1 |
trans |
NA |
| Height |
0.0522 |
0.0161 |
0.00122 |
Wald ratio |
1 |
trans |
NA |
| Childhood intelligence |
0.217 |
0.07 |
0.00189 |
Wald ratio |
1 |
trans |
NA |
| Total cholesterol |
0.0856 |
0.028 |
0.00223 |
Wald ratio |
1 |
trans |
NA |
| LDL cholesterol |
0.085 |
0.0285 |
0.00287 |
Wald ratio |
1 |
trans |
NA |
| Fasting proinsulin |
-0.108 |
0.0371 |
0.00375 |
Wald ratio |
1 |
trans |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.114 |
0.0409 |
0.00528 |
Wald ratio |
1 |
trans |
NA |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.0834 |
0.0339 |
0.0139 |
Wald ratio |
1 |
trans |
NA |
| …and 42 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4134_4_2 |
HB-EGF |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
139 association rows across 89 traits (128 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 |
| IDP dMRI TBSS ICVF Genu of corpus callosum |
4e-39 |
rs4150197 |
1 |
GCST90004329 |
no MR -> candidate analysis |
| IDP dMRI TBSS ICVF Body of corpus callosum |
3e-34 |
rs3776089 |
1 |
GCST90004330 |
no MR -> candidate analysis |
| IDP dMRI TBSS ICVF Splenium of corpus callosum |
2e-32 |
rs4150197 |
1 |
GCST90004331 |
no MR -> candidate analysis |
| HBEGF/PDGFA protein level ratio |
9e-32 |
rs2237077 |
1 |
GCST90315033 |
no MR -> candidate analysis |
| White matter microstructure (fractional anisotropy) |
4e-31 |
rs3776089 |
12 |
GCST009539 |
no MR -> candidate analysis |
| White matter microstructure (radial diusivities) |
2e-27 |
rs3776089 |
12 |
GCST009540 |
no MR -> candidate analysis |
| Circulating DLK1 levels |
4e-27 |
rs2282802 |
1 |
GCST90859946 |
no MR -> candidate analysis |
| Corpus callosum fractional anisotropy (MOSTest) |
1e-26 |
rs4150197 |
1 |
GCST90281340 |
no MR -> candidate analysis |
| IDP dMRI TBSS FA Splenium of corpus callosum |
2e-24 |
rs3776089 |
1 |
GCST90003881 |
no MR -> candidate analysis |
| Corpus callosum fractional anisotropy (splenium) |
2e-23 |
rs4150197 |
1 |
GCST90281343 |
no MR -> candidate analysis |
| IDP dMRI TBSS L2 Splenium of corpus callosum |
9e-23 |
rs3776089 |
1 |
GCST90004127 |
no MR -> candidate analysis |
| IDP dMRI ProbtrackX ICVF fmi |
2e-22 |
rs3776089 |
1 |
GCST90004386 |
no MR -> candidate analysis |
| …and 77 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 1413 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 |
| atrial fibrillation |
0.646 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.573 |
— |
common-variant locus |
no MR -> candidate analysis |
| vein disorder |
0.421 |
— |
common-variant locus |
no MR -> candidate analysis |
| Varicose veins |
0.421 |
— |
common-variant locus |
no MR -> candidate analysis |
| lymphatic system disorder |
0.421 |
— |
common-variant locus |
no MR -> candidate analysis |
| Alzheimer disease |
0.349 |
— |
common-variant locus |
no MR -> candidate analysis |
| obesity disorder |
0.283 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 7 rows above, 7 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 |
1 known modulators (Proheparin-binding EGF-like growth factor) |
| gnomAD constraint |
pLI=0.32, LOEUF=0.741 — LoF-tolerant |
| GWAS Catalog |
60 unique SNPs / 120 rows |
| ClinVar |
36 records; 6 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1413 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 ‘HBEGF’ and resolved to ‘Proheparin-binding EGF-like growth factor’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 36 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 89 traits by best p-value, aggregated from 139 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/Q99075 — 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/ENSG00000113070/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3286070/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/HBEGF — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/HBEGF — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=HBEGF%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/HBEGF — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:58:40 · 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