CausalSentinel

Protein Dossier — NPNT (Nephronectin)

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
Forced expiratory volume in 1-second (FEV1) 0.0741 0.0113 6.26e-11 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypopituitarism 1.23 0.22 2.44e-08 Wald ratio 1 cis NA
Schizophrenia 0.215 0.0704 0.00222 Wald ratio 1 cis NA
Weight 0.0349 0.0116 0.00256 Wald ratio 1 cis NA
Body mass index (BMI) 0.0371 0.0131 0.00463 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma -0.11 0.041 0.00721 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.103 0.0414 0.013 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.185 0.0774 0.0168 Wald ratio 1 cis NA
Non-cancer illness code self-reported: enlarged prostate -0.425 0.178 0.017 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0255 0.0107 0.0177 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0504 0.0212 0.0177 Wald ratio 1 cis NA
Non-cancer illness code self-reported: mania or bipolar disorder or manic depression 0.394 0.18 0.0285 Wald ratio 1 cis NA
…and 62 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

113 association rows across 72 traits (99 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
Lung function (FEV1/FVC) 4e-181 rs34712979 5 GCST007080 no MR -> candidate analysis
Chronic obstructive pulmonary disease liability (machine lea 6e-161 rs34712979 1 GCST90244098 no MR -> candidate analysis
FEV1 FVC ratio Z score (UKB data field 20258) 4e-146 rs34712979 1 GCST90468165 no MR -> candidate analysis
FEV1/FVC ratio 9e-141 rs34712979 1 GCST90705072 no MR -> candidate analysis
Forced expiratory volume in 1 second (FEV1) 2e-110 rs34712979 1 GCST90705070 no MR -> candidate analysis
Forced expiratory volume in 1 second FEV1 Z score (UKB data 7e-98 rs34712979 1 GCST90468166 no MR -> candidate analysis
FEV1 9e-97 rs34712979 1 GCST007432 MR: beta=0.0741, p=6.26e-11 (cis)
Forced expiratory volume (baseline) 3e-64 rs34712979 2 GCST90565844 no MR -> candidate analysis
Peak expiratory flow 2e-51 rs34712979 2 GCST007430 no MR -> candidate analysis
Serum levels of protein NPNT 6e-50 rs34712979 1 GCST90089355 no MR -> candidate analysis
Chronic obstructive pulmonary disease 3e-46 rs34712979 3 GCST007692 no MR -> candidate analysis
Chronic obstructive pulmonary disease x ever smoker interact 8e-43 rs34712979 1 GCST90016585 no MR -> candidate analysis
…and 60 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 213 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
chronic obstructive pulmonary disease 0.904 common-variant locus no MR -> candidate analysis
asthma 0.893 common-variant locus MR: beta=-0.11, p=0.00721 (cis)
lower respiratory tract disorder 0.728 common-variant locus no MR -> candidate analysis
respiratory system disorder 0.719 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.692 common-variant locus no MR -> candidate analysis
essential hypertension 0.632 common-variant locus no MR -> candidate analysis
major depressive disorder 0.603 common-variant locus no MR -> candidate analysis
Chronic Obstructive Asthma 0.593 common-variant locus no MR -> candidate analysis
COVID-19 0.573 common-variant locus no MR -> candidate analysis
cardiovascular disorder 0.584 common-variant locus no MR -> candidate analysis
chronic rhinosinusitis 0.573 common-variant locus no MR -> candidate analysis
aging 0.574 common-variant locus no MR -> candidate analysis
Increased blood pressure 0.535 common-variant locus no MR -> candidate analysis
glaucoma 0.535 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.535 common-variant locus MR: beta=0.103, p=0.366 (cis)

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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=4e-10, LOEUF=0.841 — LoF-tolerant
GWAS Catalog 52 unique SNPs / 92 rows
ClinVar 149 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance