Protein Dossier — FN1 (Fibronectin)
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 |
| Systolic blood pressure automated reading |
-0.0265 |
0.00393 |
1.70e-11 |
Wald ratio |
1 |
cis |
NA |
| LDL cholesterol |
0.0342 |
0.0059 |
7.22e-09 |
Wald ratio |
1 |
cis |
NA |
| Total cholesterol |
0.0299 |
0.00576 |
2.05e-07 |
Wald ratio |
1 |
cis |
NA |
| Coronary heart disease |
-0.0461 |
0.0152 |
0.00246 |
Wald ratio |
1 |
cis |
NA |
| Large vessel disease |
-0.166 |
0.0558 |
0.00288 |
Wald ratio |
1 |
cis |
NA |
| Height |
-0.0141 |
0.00492 |
0.00427 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level |
0.359 |
0.13 |
0.00571 |
Wald ratio |
1 |
cis |
NA |
| Myocardial infarction |
-0.043 |
0.0162 |
0.00815 |
Wald ratio |
1 |
cis |
NA |
| Squamous cell lung cancer |
0.104 |
0.0428 |
0.0152 |
Wald ratio |
1 |
cis |
NA |
| Triglycerides |
0.0125 |
0.00534 |
0.0192 |
Wald ratio |
1 |
cis |
NA |
| Vascular or heart problems diagnosed by doctor: Angina |
-0.0528 |
0.0227 |
0.02 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: retinal detachment |
0.132 |
0.0589 |
0.025 |
Wald ratio |
1 |
cis |
NA |
| …and 104 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3434_34_1 |
FN1.3 |
Suhre K |
2019 |
prot-c-3435_53_2 |
FN1.4 |
Suhre K |
2019 |
prot-c-4131_72_2 |
Fibronectin |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
170 association rows across 85 traits (153 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 |
| Serum levels of protein FN1 |
2e-153 |
rs1250258 |
3 |
GCST90088589 |
no MR -> candidate analysis |
| Circulating ITGA5 levels |
1e-108 |
rs139078629 |
4 |
GCST90860638 |
no MR -> candidate analysis |
| Height |
3e-107 |
rs1250258 |
10 |
GCST90245848 |
MR: beta=-0.0141, p=0.00427 (cis) |
| ITGA5 protein levels |
1e-104 |
rs139078629 |
5 |
GCST90469635 |
no MR -> candidate analysis |
| Serum levels of protein NPNT |
6e-94 |
rs1250259 |
1 |
GCST90089355 |
no MR -> candidate analysis |
| Blood protein levels |
5e-89 |
rs1250259 |
9 |
GCST006585 |
no MR -> candidate analysis |
| Fibronectin Fragment 3 levels |
1e-49 |
rs1250258 |
3 |
GCST90101019 |
no MR -> candidate analysis |
| cFib plasma levels |
4e-47 |
rs1132741 |
1 |
GCST90085720 |
no MR -> candidate analysis |
| Fibronectin levels |
5e-46 |
rs1250258 |
2 |
GCST90161975 |
no MR -> candidate analysis |
| Fibronectin Fragment 4 levels |
2e-42 |
rs1250258 |
3 |
GCST90101020 |
no MR -> candidate analysis |
| FN1 protein levels |
2e-40 |
rs3845846 |
6 |
GCST90469255 |
no MR -> candidate analysis |
| Pulse pressure |
8e-35 |
rs1250259 |
11 |
GCST90310296 |
no MR -> candidate analysis |
| …and 73 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 1798 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 |
| spondylometaphyseal dysplasia, ‘corner fracture’ type |
0.88 |
— |
established (curated) |
no MR -> candidate analysis |
| glomerulopathy with fibronectin deposits 2 |
0.882 |
— |
established (curated) |
no MR -> candidate analysis |
| coronary artery disorder |
0.928 |
— |
common-variant locus |
no MR -> candidate analysis |
| fibronectin glomerulopathy |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| coronary atherosclerosis |
0.781 |
— |
common-variant locus |
no MR -> candidate analysis |
| myocardial infarction |
0.743 |
— |
common-variant locus |
MR: beta=-0.043, p=0.00815 (cis) |
| Abnormality of the skeletal system |
0.758 |
— |
common-variant locus |
no MR -> candidate analysis |
| myocardial ischemia |
0.744 |
— |
common-variant locus |
no MR -> candidate analysis |
| hereditary disease |
0.684 |
— |
established (curated) |
no MR -> candidate analysis |
| spondylometaphyseal dysplasia |
0.663 |
— |
established (curated) |
no MR -> candidate analysis |
| occlusion precerebral artery |
0.599 |
— |
common-variant locus |
no MR -> candidate analysis |
| angina pectoris |
0.595 |
— |
common-variant locus |
no MR -> candidate analysis |
| coronary artery bypass |
0.521 |
— |
common-variant locus |
no MR -> candidate analysis |
| benign prostatic hyperplasia |
0.484 |
— |
common-variant locus |
no MR -> candidate analysis |
| neurodevelopmental disorder |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
Of the 15 rows above, 14 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 |
2 known modulators (Coagulation factor XII) |
| gnomAD constraint |
pLI=1, LOEUF=0.419 — LoF-INTOLERANT |
| GWAS Catalog |
66 unique SNPs / 132 rows |
| ClinVar |
2067 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1798 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 ‘FN1’ and resolved to ‘Coagulation factor XII’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 2067 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 85 traits by best p-value, aggregated from 170 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/P02751 — 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/ENSG00000115414/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2821/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/FN1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/FN1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=FN1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/FN1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:42:22 · 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