Protein Dossier — SPON1 (Spondin-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 |
| Diastolic blood pressure automated reading |
0.0323 |
0.00657 |
8.51e-07 |
Wald ratio |
1 |
cis |
NA |
| Pulse rate |
0.0538 |
0.0113 |
1.99e-06 |
Wald ratio |
1 |
cis |
NA |
| Height |
-0.0347 |
0.00774 |
7.37e-06 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I48 Atrial fibrillation and flutter |
0.169 |
0.0514 |
0.00103 |
Wald ratio |
1 |
cis |
NA |
| HbA1C |
0.0275 |
0.00907 |
0.00245 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level |
0.55 |
0.183 |
0.00267 |
Wald ratio |
1 |
cis |
NA |
| Internalizing problems |
-0.173 |
0.0592 |
0.00351 |
Wald ratio |
1 |
cis |
NA |
| Forced vital capacity (FVC) |
-0.0151 |
0.00526 |
0.00418 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0141 |
0.00555 |
0.011 |
Wald ratio |
1 |
cis |
NA |
| Lung cancer |
-0.113 |
0.0456 |
0.0136 |
Wald ratio |
1 |
cis |
NA |
| Alcohol intake frequency |
0.0233 |
0.00948 |
0.0141 |
Wald ratio |
1 |
cis |
NA |
| Bulimia nervosa |
-0.0454 |
0.0187 |
0.0152 |
Wald ratio |
1 |
cis |
NA |
| …and 87 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4297_62_3 |
Spondin-1 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
135 association rows across 67 traits (118 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 |
| Circulating SPON1 levels |
3e-675 |
rs1406355 |
4 |
GCST90859947 |
no MR -> candidate analysis |
| ROBO1/SPON1 protein level ratio |
2e-518 |
rs11023059 |
1 |
GCST90315783 |
no MR -> candidate analysis |
| Bone mineral density mean |
1e-300 |
rs118102517 |
1 |
GCST90321120 |
no MR -> candidate analysis |
| Spondin-1 levels |
9e-192 |
rs1969539 |
11 |
GCST90249641 |
no MR -> candidate analysis |
| Height |
1e-103 |
rs2303973 |
5 |
GCST90245848 |
MR: beta=-0.0347, p=7.37e-06 (cis) |
| Vitamin D levels |
1e-101 |
rs72632971 |
11 |
GCST90019526 |
no MR -> candidate analysis |
| SPON1 protein levels |
3e-83 |
rs55917787 |
9 |
GCST90470731 |
no MR -> candidate analysis |
| Spondin-1 levels (SPON1.4297.62.3) |
1e-55 |
rs10832169 |
1 |
GCST90242886 |
no MR -> candidate analysis |
| Serum 25-Hydroxyvitamin D levels |
5e-43 |
rs561089663 |
5 |
GCST010144 |
no MR -> candidate analysis |
| Serum levels of protein SPON1 |
1e-35 |
rs11023063 |
2 |
GCST90088655 |
no MR -> candidate analysis |
| Serum 25-Hydroxyvitamin D levels (summer) |
2e-35 |
rs2618515 |
3 |
GCST90000619 |
no MR -> candidate analysis |
| Blood protein levels in cardiovascular risk |
8e-34 |
rs1969539 |
1 |
GCST009731 |
no MR -> candidate analysis |
| …and 55 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 513 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 |
| atrial fibrillation |
0.848 |
— |
common-variant locus |
MR: beta=0.169, p=0.00103 (cis) |
| hypertrophic cardiomyopathy |
0.599 |
— |
common-variant locus |
no MR -> candidate analysis |
| lagophthalmos |
0.506 |
— |
common-variant locus |
no MR -> candidate analysis |
| response to TNF antagonist |
0.5 |
— |
common-variant locus |
no MR -> candidate analysis |
| adolescent idiopathic scoliosis |
0.492 |
— |
common-variant locus |
no MR -> candidate analysis |
| response to paracetamol |
0.447 |
— |
common-variant locus |
no MR -> candidate analysis |
| rotator cuff syndrome |
0.447 |
— |
common-variant locus |
no MR -> candidate analysis |
| post term pregnancy |
0.431 |
— |
common-variant locus |
no MR -> candidate analysis |
| diabetes mellitus |
0.423 |
— |
common-variant locus |
no MR -> candidate analysis |
| major salivary gland cancer |
0.411 |
— |
common-variant locus |
no MR -> candidate analysis |
| vitamin D deficiency |
0.384 |
— |
common-variant locus |
no MR -> candidate analysis |
| vitamin deficiency disorder |
0.38 |
— |
common-variant locus |
no MR -> candidate analysis |
| autoimmune thyroid disease |
0.334 |
— |
common-variant locus |
no MR -> candidate analysis |
| Alzheimer disease |
0.307 |
— |
common-variant locus |
no MR -> candidate analysis |
| clavicle fracture |
0.324 |
— |
common-variant locus |
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 |
not available — no ChEMBL target (undrugged) |
| gnomAD constraint |
pLI=0.00017, LOEUF=0.586 — LoF-tolerant |
| GWAS Catalog |
119 unique SNPs / 284 rows |
| ClinVar |
100 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 513 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 ‘SPON1’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 100 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 67 traits by best p-value, aggregated from 135 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/Q9HCB6 — 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/ENSG00000262655/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/SPON1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SPON1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SPON1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SPON1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:13:48 · 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