Protein Dossier — NRP1 (Protein kinase C-binding protein NELL1)
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 |
| ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.113 |
0.0351 |
0.00124 |
Inverse variance weighted |
2 |
trans |
NA |
| ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.113 |
0.0351 |
0.00124 |
Inverse variance weighted |
2 |
cis |
NA |
| Coronary heart disease |
-0.0969 |
0.0303 |
0.00141 |
Inverse variance weighted |
2 |
trans |
NA |
| Coronary heart disease |
-0.0969 |
0.0303 |
0.00141 |
Inverse variance weighted |
2 |
cis |
NA |
| Primary sclerosing cholangitis |
0.293 |
0.0949 |
0.00205 |
Inverse variance weighted |
2 |
trans |
NA |
| Primary sclerosing cholangitis |
0.293 |
0.0949 |
0.00205 |
Inverse variance weighted |
2 |
cis |
NA |
| Vascular or heart problems diagnosed by doctor: Angina |
-0.141 |
0.048 |
0.00331 |
Inverse variance weighted |
2 |
trans |
NA |
| Vascular or heart problems diagnosed by doctor: Angina |
-0.141 |
0.048 |
0.00331 |
Inverse variance weighted |
2 |
cis |
NA |
| Myocardial infarction |
-0.0908 |
0.0311 |
0.0035 |
Inverse variance weighted |
2 |
trans |
NA |
| Myocardial infarction |
-0.0908 |
0.0311 |
0.0035 |
Inverse variance weighted |
2 |
cis |
NA |
| Hip osteoarthritis |
0.233 |
0.0857 |
0.00661 |
Inverse variance weighted |
2 |
trans |
NA |
| Hip osteoarthritis |
0.233 |
0.0857 |
0.00661 |
Inverse variance weighted |
2 |
cis |
NA |
| …and 204 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3214_3_2 |
NRP1 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
176 association rows across 108 traits (135 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 NRP1 levels |
8e-557 |
rs734186 |
4 |
GCST90860421 |
no MR -> candidate analysis |
| Neuropilin-1 levels |
5e-115 |
rs2506150 |
3 |
GCST90248732 |
no MR -> candidate analysis |
| NRP1 protein levels |
6e-57 |
rs111793120 |
12 |
GCST90470085 |
no MR -> candidate analysis |
| Serum levels of protein NRP1 |
4e-40 |
rs2474720 |
2 |
GCST90089072 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein NRP1 levels |
1e-38 |
rs734186 |
1 |
GCST90945026 |
no MR -> candidate analysis |
| Vertex-wise sulcal depth |
2e-34 |
rs2506141 |
2 |
GCST90095129 |
no MR -> candidate analysis |
| Neuropilin-1 (analyte X5542.22) levels |
3e-30 |
rs2506149 |
1 |
GCST90426380 |
no MR -> candidate analysis |
| Neuropilin-1 (analyte X3214.3) levels |
4e-29 |
rs2506149 |
1 |
GCST90425658 |
no MR -> candidate analysis |
| Neuropilin-1 levels (NRP1.3214.3.2) |
7e-28 |
rs2506149 |
1 |
GCST90242093 |
no MR -> candidate analysis |
| High-density lipoprotein levels |
5e-27 |
rs3750733 |
1 |
GCST90662894 |
no MR -> candidate analysis |
| Blood protein levels |
3e-25 |
rs2253918 |
2 |
GCST006585 |
no MR -> candidate analysis |
| High density lipoprotein cholesterol levels |
1e-23 |
rs10827239 |
2 |
GCST90239649 |
no MR -> candidate analysis |
| …and 96 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 1331 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 |
| migraine disorder |
0.561 |
— |
common-variant locus |
no MR -> candidate analysis |
| obstructive sleep apnea syndrome |
0.563 |
— |
common-variant locus |
no MR -> candidate analysis |
| health study participation |
0.55 |
— |
common-variant locus |
no MR -> candidate analysis |
| mathematical ability |
0.549 |
— |
common-variant locus |
no MR -> candidate analysis |
| nerve plexus disorder |
0.537 |
— |
common-variant locus |
no MR -> candidate analysis |
| ovarian neoplasm |
0.523 |
— |
common-variant locus |
no MR -> candidate analysis |
| metabolic disease |
0.524 |
— |
common-variant locus |
no MR -> candidate analysis |
| digestive system disorder |
0.497 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.497 |
— |
common-variant locus |
no MR -> candidate analysis |
| Barrett esophagus |
0.428 |
— |
common-variant locus |
no MR -> candidate analysis |
| placenta praevia |
0.407 |
— |
common-variant locus |
no MR -> candidate analysis |
| corneal neovascularization |
0.406 |
— |
common-variant locus |
no MR -> candidate analysis |
| liver disorder |
0.391 |
— |
common-variant locus |
no MR -> candidate analysis |
| jaw disease |
0.391 |
— |
common-variant locus |
no MR -> candidate analysis |
| medical procedure |
0.387 |
— |
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 |
0 known modulators (VEGA-NRP1) |
| gnomAD constraint |
pLI=1, LOEUF=0.435 — LoF-INTOLERANT |
| GWAS Catalog |
108 unique SNPs / 225 rows |
| ClinVar |
360 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
1 clinical annotations across 1 drugs |
phenome — Top 30 of 1331 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 ‘NRP1’ and resolved to ‘VEGA-NRP1’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 360 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 108 traits by best p-value, aggregated from 176 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/Q92832 — 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/ENSG00000099250/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL5482974/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/NRP1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/NRP1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=NRP1%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=NRP1 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/NRP1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:04:41 · 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