Protein Dossier — NTN4 (Netrin-4)
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 |
| Myocardial infarction |
0.147 |
0.054 |
0.00634 |
Wald ratio |
1 |
cis |
NA |
| Coronary heart disease |
0.128 |
0.0483 |
0.00792 |
Wald ratio |
1 |
cis |
NA |
| 2hr glucose |
0.234 |
0.0936 |
0.0124 |
Wald ratio |
1 |
cis |
NA |
| Primary sclerosing cholangitis |
-0.382 |
0.162 |
0.0183 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hayfever or allergic rhinitis |
-0.124 |
0.0529 |
0.0189 |
Wald ratio |
1 |
cis |
NA |
| Platelet count |
4.7 |
2.14 |
0.0283 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Ankle |
-0.286 |
0.131 |
0.0297 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I83 Varicose veins of lower extremities |
0.149 |
0.0685 |
0.03 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M72 Fibroblastic disorders |
0.256 |
0.121 |
0.0345 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux |
0.104 |
0.0493 |
0.035 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K57 Diverticular disease of intestine |
-0.194 |
0.0978 |
0.0475 |
Wald ratio |
1 |
cis |
NA |
| Percent emphysema |
-0.131 |
0.0673 |
0.0522 |
Wald ratio |
1 |
cis |
NA |
| …and 93 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3327_27_1 |
NET4 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
47 association rows across 37 traits (34 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-4 levels |
3e-54 |
rs17288108 |
3 |
GCST90248644 |
no MR -> candidate analysis |
| Serum levels of protein NTN4 |
4e-23 |
rs17288108 |
1 |
GCST90088319 |
no MR -> candidate analysis |
| Histidine levels |
2e-21 |
rs61938133 |
1 |
GCST90827777 |
no MR -> candidate analysis |
| Netrin-4 levels (NTN4.3327.27.1) |
7e-18 |
rs17288108 |
1 |
GCST90242049 |
no MR -> candidate analysis |
| Serum urate levels |
6e-17 |
rs17287370 |
3 |
GCST90455669 |
no MR -> candidate analysis |
| Photoreceptor cell layer thickness phenotypes (MTAG) |
3e-16 |
rs76629482 |
1 |
GCST90255614 |
no MR -> candidate analysis |
| Urate levels (UKB data field 30880) |
3e-15 |
rs11108210 |
1 |
GCST90468107 |
no MR -> candidate analysis |
| Histidine levels (UKB data field 23463) |
7e-15 |
rs61938133 |
1 |
GCST90269560 |
no MR -> candidate analysis |
| Urate levels |
1e-13 |
rs12423171 |
2 |
GCST011119 |
no MR -> candidate analysis |
| Cortical surface area |
7e-13 |
rs6538668 |
1 |
GCST90091060 |
no MR -> candidate analysis |
| Blood protein levels |
2e-12 |
rs17288108 |
1 |
GCST006585 |
no MR -> candidate analysis |
| Circulating HAVCR1 levels (id: OID00426_OID21422) |
2e-12 |
rs34519397 |
1 |
GCST90859787 |
no MR -> candidate analysis |
| …and 25 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 510 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 |
| gout |
0.796 |
— |
common-variant locus |
MR: beta=0.157, p=0.0556 (cis) |
| colorectal cancer |
0.565 |
— |
common-variant locus |
no MR -> candidate analysis |
| hearing loss disorder |
0.549 |
— |
common-variant locus |
no MR -> candidate analysis |
| Sensorineural hearing impairment |
0.538 |
— |
common-variant locus |
no MR -> candidate analysis |
| benign colon neoplasm |
0.531 |
— |
common-variant locus |
MR: beta=-0.124, p=0.259 (cis) |
| polyp of colon |
0.474 |
— |
common-variant locus |
no MR -> candidate analysis |
| gastroesophageal reflux disease |
0.441 |
— |
common-variant locus |
no MR -> candidate analysis |
| renal carcinoma |
0.437 |
— |
common-variant locus |
no MR -> candidate analysis |
| placenta praevia |
0.421 |
— |
common-variant locus |
no MR -> candidate analysis |
| adolescent idiopathic scoliosis |
0.418 |
— |
common-variant locus |
no MR -> candidate analysis |
| gastric ulcer |
0.396 |
— |
common-variant locus |
no MR -> candidate analysis |
| hemorrhage |
0.396 |
— |
common-variant locus |
no MR -> candidate analysis |
| chronic obstructive pulmonary disease |
0.284 |
— |
common-variant locus |
no MR -> candidate analysis |
| breast carcinoma |
0.241 |
— |
common-variant locus |
no MR -> candidate analysis |
| breast cancer |
0.226 |
— |
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 |
not available — no ChEMBL target (undrugged) |
| gnomAD constraint |
pLI=0.039, LOEUF=0.584 — LoF-tolerant |
| GWAS Catalog |
84 unique SNPs / 168 rows |
| ClinVar |
92 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 510 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — No ChEMBL target for ‘NTN4’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 92 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 37 traits by best p-value, aggregated from 47 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/Q9HB63 — 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/ENSG00000074527/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/NTN4 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/NTN4 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=NTN4%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/NTN4 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:06:20 · 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