CausalSentinel

Protein Dossier — NTN1 (Netrin-1)

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
Diagnoses - main ICD10: B37 Candidiasis 0.528 0.192 0.00603 Wald ratio 1 cis NA
Putamen volume 42.4 16.1 0.00826 Wald ratio 1 cis NA
Cough on most days 0.0768 0.0312 0.0137 Wald ratio 1 cis NA
Systemic lupus erythematosus -0.289 0.128 0.0241 Wald ratio 1 cis NA
Femoral neck bone mineral density 0.0448 0.0208 0.031 Wald ratio 1 cis NA
Systolic blood pressure automated reading 0.0144 0.0067 0.0312 Wald ratio 1 cis NA
LDL cholesterol -0.0297 0.0138 0.0316 Wald ratio 1 cis NA
Lung adenocarcinoma -0.166 0.0782 0.0333 Wald ratio 1 cis NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.442 0.211 0.0357 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.014 0.0067 0.0361 Wald ratio 1 cis NA
Fasting proinsulin -0.0363 0.019 0.0563 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertrophic cardiomyopathy (hcm or hocm) 0.554 0.291 0.0567 Wald ratio 1 cis NA
…and 104 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

130 association rows across 79 traits (94 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
Netrin-1 levels 1e-184 rs9897200 7 GCST90248643 no MR -> candidate analysis
Serum levels of protein NTN1 9e-84 rs10468483 4 GCST90090447 no MR -> candidate analysis
Blood protein levels 5e-53 rs72809988 2 GCST006585 no MR -> candidate analysis
Netrin-1 levels (NTN1.6649.51.3) 2e-52 rs72809988 2 GCST90242047 no MR -> candidate analysis
Vertex-wise sulcal depth 2e-40 rs80100171 1 GCST90095129 no MR -> candidate analysis
Netrin-1 (analyte X6649.51) levels 1e-39 rs9894560 1 GCST90426808 no MR -> candidate analysis
Estimated bone mineral density 5e-39 rs56235417 4 GCST90726625 no MR -> candidate analysis
Height 7e-39 rs3744656 3 GCST90245848 no MR -> candidate analysis
Heel bone mineral density 1e-36 rs56235417 10 GCST006979 MR: beta=-0.0121, p=0.155 (cis)
Netrin-1 (analyte X9013.60) levels 3e-34 rs9894560 1 GCST90427601 no MR -> candidate analysis
Whole brain restricted directional diffusion (multivariate a 1e-23 rs56235417 1 GCST90131905 no MR -> candidate analysis
Unsupervised deep imaging phenotypes (UDIP-FA) 4e-23 rs1107361 2 GCST90860937 no MR -> candidate analysis
…and 67 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 1462 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
mirror movements 4 0.816 established (curated) no MR -> candidate analysis
cleft palate 0.613 established (curated) no MR -> candidate analysis
cleft lip 0.613 established (curated) no MR -> candidate analysis
orofacial cleft 0.559 established (curated) no MR -> candidate analysis
familial congenital mirror movements 0.608 established (curated) no MR -> candidate analysis
lacrimal apparatus disorder 0.566 common-variant locus no MR -> candidate analysis
placental abruption 0.474 common-variant locus no MR -> candidate analysis
multinodular goiter 0.469 common-variant locus no MR -> candidate analysis
sweat gland disorder 0.462 common-variant locus no MR -> candidate analysis
response to antihypertensive drug 0.459 common-variant locus no MR -> candidate analysis
lens disorder 0.458 common-variant locus no MR -> candidate analysis
color vision disorder 0.444 common-variant locus no MR -> candidate analysis
bone remodeling disease 0.441 common-variant locus no MR -> candidate analysis
hemorrhoid 0.431 common-variant locus no MR -> candidate analysis
Tietze syndrome 0.431 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 (Netrin-1)
gnomAD constraint pLI=1, LOEUF=0.336 — LoF-INTOLERANT
GWAS Catalog 106 unique SNPs / 235 rows
ClinVar 140 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance