MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
| Outcome | beta | se | p | method | nSNP | cis/trans | coloc |
|---|---|---|---|---|---|---|---|
| Heel bone mineral density (BMD) T-score automated | -0.118 | 0.0157 | 6.09e-14 | Wald ratio | 1 | cis | NA |
| Fractured or broken bones in last 5 years | -0.166 | 0.0447 | 2.11e-04 | Wald ratio | 1 | cis | NA |
| Knee osteoarthritis | -0.443 | 0.144 | 0.00213 | Wald ratio | 1 | cis | NA |
| Forced expiratory volume in 1-second (FEV1) | -0.0321 | 0.0105 | 0.0022 | Wald ratio | 1 | cis | NA |
| Fractured bone site(s): Other bones | -0.188 | 0.0639 | 0.00328 | Wald ratio | 1 | cis | NA |
| Forced vital capacity (FVC) | -0.0283 | 0.00994 | 0.00445 | Wald ratio | 1 | cis | NA |
| Weight | -0.0295 | 0.0107 | 0.00579 | Wald ratio | 1 | cis | NA |
| Lumbar spine bone mineral density | -0.116 | 0.0443 | 0.00892 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: enlarged prostate | 0.213 | 0.0843 | 0.0114 | Wald ratio | 1 | cis | NA |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) | 0.0784 | 0.0324 | 0.0155 | Wald ratio | 1 | cis | NA |
| Knee and hip osteoarthritis | -0.241 | 0.101 | 0.017 | Wald ratio | 1 | cis | NA |
| Fasting proinsulin | 0.0845 | 0.0357 | 0.0179 | Wald ratio | 1 | cis | NA |
| …and 97 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
26 association rows across 21 traits (23 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 |
|---|---|---|---|---|---|
| FSTL3/SPON2 protein level ratio | 5e-301 | rs6836335 | 1 | GCST90314884 | no MR -> candidate analysis |
| NECTIN2/SPON2 protein level ratio | 1e-300 | rs6836335 | 1 | GCST90315530 | no MR -> candidate analysis |
| B4GALT1/SPON2 protein level ratio | 4e-269 | rs6836335 | 1 | GCST90313434 | no MR -> candidate analysis |
| COL6A3/SPON2 protein level ratio | 1e-266 | rs6836335 | 1 | GCST90314179 | no MR -> candidate analysis |
| GFRA1/SPON2 protein level ratio | 2e-235 | rs6836335 | 1 | GCST90314923 | no MR -> candidate analysis |
| SPON2 protein levels | 8e-232 | rs6836335 | 2 | GCST90470732 | no MR -> candidate analysis |
| Spondin-2 levels | 2e-84 | rs11731643 | 2 | GCST90427266 | no MR -> candidate analysis |
| SPON2 protein level (protein group normalized intensity) | 8e-37 | rs11247975 | 1 | GCST90570755 | no MR -> candidate analysis |
| Estimated bone mineral density | 6e-23 | rs544491543 | 1 | GCST90726625 | no MR -> candidate analysis |
| Whole body fat free mass (UKB data field 23101) | 6e-17 | rs113963956 | 1 | GCST90428120 | no MR -> candidate analysis |
| Blood protein levels | 2e-16 | rs878323 | 1 | GCST006585 | no MR -> candidate analysis |
| Circulating SPON2 levels | 8e-16 | rs545410362 | 1 | GCST90859778 | no MR -> candidate analysis |
| …and 9 more traits (see JSON) |
Top diseases by Open Targets association (of 254 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 |
|---|---|---|---|---|
| Abnormality of the skeletal system | 0.787 | — | common-variant locus | no MR -> candidate analysis |
| Back pain | 0.561 | — | common-variant locus | no MR -> candidate analysis |
| atrial fibrillation | 0.541 | — | common-variant locus | no MR -> candidate analysis |
| vertebral column disorder | 0.538 | — | common-variant locus | no MR -> candidate analysis |
| osteoarthritis, knee | 0.51 | — | common-variant locus | MR: beta=-0.443, p=0.00213 (cis) |
| Intervertebral disk degeneration | 0.421 | — | common-variant locus | no MR -> candidate analysis |
| vertebral joint disorder | 0.412 | — | common-variant locus | no MR -> candidate analysis |
| osteoarthritis, hip | 0.397 | — | common-variant locus | MR: beta=-0.241, p=0.017 (cis) |
| musculoskeletal system disorder | 0.275 | — | common-variant locus | no MR -> candidate analysis |
| gastroesophageal reflux disease | 0.235 | — | common-variant locus | no MR -> candidate analysis |
| medical procedure | 0.168 | — | common-variant locus | no MR -> candidate analysis |
| sunburn | 0.113 | — | common-variant locus | no MR -> candidate analysis |
Of the 12 rows above, 10 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.
| Layer | Result |
|---|---|
| ChEMBL druggability | not available — no ChEMBL target (undrugged) |
| gnomAD constraint | pLI=3.6e-12, LOEUF=1.44 — LoF-tolerant |
| GWAS Catalog | 68 unique SNPs / 136 rows |
| ClinVar | 252 records; 10 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 254 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 ‘SPON2’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 252 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 21 traits by best p-value, aggregated from 26 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.uniprot: https://www.uniprot.org/uniprotkb/Q9BUD6 — 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/ENSG00000159674/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/SPON2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SPON2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SPON2%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SPON2 — GWAS Catalog search API (live; release not exposed)