CausalSentinel

Protein Dossier — NRP2 (Protein kinase C-binding protein NELL2)

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
Small vessel disease -0.57 0.184 0.00194 Wald ratio 1 cis NA
Diagnoses - main ICD10: M23 Internal derangement of knee 0.208 0.068 0.0022 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux 0.148 0.0516 0.00413 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia 0.178 0.0637 0.00522 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] 0.19 0.0742 0.0103 Wald ratio 1 cis NA
Fasting glucose -0.0425 0.0177 0.0162 Wald ratio 1 cis NA
Gallbladder cancer 2.78 1.17 0.0176 Wald ratio 1 cis NA
Diagnoses - main ICD10: K20 Oesophagitis 0.228 0.101 0.0234 Wald ratio 1 cis NA
Bulimia nervosa 0.0955 0.043 0.0263 Wald ratio 1 cis NA
Eye problems or disorders: Cataract -0.17 0.0809 0.036 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis 0.143 0.0699 0.0412 Wald ratio 1 cis NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis 0.197 0.0972 0.0426 Wald ratio 1 cis NA
…and 97 more outcomes (see JSON)              

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

47 association rows across 33 traits (35 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
NRP2 protein levels 1e-135 rs16837641 9 GCST90470086 no MR -> candidate analysis
Circulating NRP2 levels 3e-132 rs16837641 5 GCST90859655 no MR -> candidate analysis
Neuropilin-2 levels 2e-25 rs16837641 1 GCST90248733 no MR -> candidate analysis
Type 2 diabetes 3e-20 rs3771003 1 GCST90134620 MR: beta=0.0946, p=0.187 (cis)
Circulating SEMA3F levels 2e-15 rs2160327 1 GCST90860355 no MR -> candidate analysis
ADAM23 protein levels 3e-15 rs10188991 2 GCST90468219 no MR -> candidate analysis
Neuropilin-2 levels (NRP2.6590.54.3) 1e-14 rs16837641 1 GCST90242094 no MR -> candidate analysis
Vertex-wise sulcal depth 2e-14 rs863707 1 GCST90095129 no MR -> candidate analysis
GLIPR1 protein levels 3e-14 rs183879700 1 GCST90469357 no MR -> candidate analysis
Meningitis (PheCode 320) 3e-12 rs543029525 1 GCST90479995 no MR -> candidate analysis
SEMA3F protein levels 3e-12 rs2160327 1 GCST90470570 no MR -> candidate analysis
Male-pattern baldness 7e-11 rs1861386 1 GCST007020 no MR -> candidate analysis
…and 21 more traits (see JSON)          

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 1672 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
esophageal disorder 0.666 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.616 common-variant locus no MR -> candidate analysis
glaucoma 0.542 common-variant locus MR: beta=-0.112, p=0.341 (cis)
femoral neck fracture 0.542 common-variant locus no MR -> candidate analysis
Jaundice 0.537 common-variant locus no MR -> candidate analysis
gastroesophageal reflux disease 0.536 common-variant locus no MR -> candidate analysis
flatulence 0.534 common-variant locus no MR -> candidate analysis
osteomyelitis 0.51 common-variant locus no MR -> candidate analysis
food allergy 0.506 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.491 common-variant locus no MR -> candidate analysis
infectious meningitis 0.482 common-variant locus no MR -> candidate analysis
cholelithiasis 0.482 common-variant locus MR: beta=-0.0707, p=0.449 (cis)
hereditary disease 0.438 established (curated) no MR -> candidate analysis
parasitic infectious disease 0.323 common-variant locus no MR -> candidate analysis
alcohol drinking 0.274 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 13 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 (NRP2-VEGA)
gnomAD constraint pLI=8.5e-05, LOEUF=0.594 — LoF-tolerant
GWAS Catalog 120 unique SNPs / 282 rows
ClinVar 430 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance