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 | 0.222 | 0.0116 | 1.80e-82 | Wald ratio | 1 | cis | 0.000535 |
| HDL cholesterol | -0.0733 | 0.0126 | 5.76e-09 | Wald ratio | 1 | cis | 0.977 |
| Crohn’s disease | 0.243 | 0.0447 | 5.55e-08 | Wald ratio | 1 | cis | 1 |
| Fractured or broken bones in last 5 years | -0.168 | 0.033 | 3.37e-07 | Wald ratio | 1 | cis | 0.0762 |
| Triglycerides | 0.0611 | 0.0122 | 5.73e-07 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: I83 Varicose veins of lower extremities | -0.405 | 0.0945 | 1.80e-05 | Wald ratio | 1 | cis | NA |
| Inflammatory bowel disease | 0.152 | 0.0369 | 3.70e-05 | Wald ratio | 1 | cis | NA |
| Fasting insulin | 0.0481 | 0.0119 | 4.85e-05 | Wald ratio | 1 | cis | NA |
| Birth weight | 0.0507 | 0.0133 | 1.41e-04 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: hypertension | -0.0586 | 0.0161 | 2.84e-04 | Wald ratio | 1 | cis | NA |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) | -0.0793 | 0.0233 | 6.82e-04 | Wald ratio | 1 | cis | NA |
| Fractured bone site(s): Other bones | -0.149 | 0.0452 | 0.00101 | Wald ratio | 1 | cis | NA |
| …and 128 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
1770 association rows across 740 traits (1681 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 |
|---|---|---|---|---|---|
| Estimated bone mineral density | 5e-443 | rs7741021 | 2 | GCST90726625 | no MR -> candidate analysis |
| Heel bone mineral density | 2e-369 | rs7741021 | 22 | GCST006433 | MR: beta=0.222, p=1.80e-82 (cis) |
| Waist-to-hip ratio adjusted for BMI | 2e-293 | rs72959041 | 62 | GCST008994 | no MR -> candidate analysis |
| Body shape phenotype PC3 | 1e-277 | rs72959041 | 1 | GCST90832991 | no MR -> candidate analysis |
| Waist-hip ratio | 1e-274 | rs577721086 | 14 | GCST007067 | no MR -> candidate analysis |
| Waist-hip index | 2e-243 | rs72959041 | 34 | GCST90020027 | no MR -> candidate analysis |
| R-spondin-3 levels | 6e-158 | rs4644087 | 7 | GCST90249393 | no MR -> candidate analysis |
| Circulating RSPO3 levels | 7e-150 | rs1936800 | 4 | GCST90860078 | no MR -> candidate analysis |
| RSPO3 protein levels | 3e-144 | rs1936800 | 4 | GCST90470504 | no MR -> candidate analysis |
| Waist circumference adjusted for body mass index | 5e-126 | rs72959041 | 39 | GCST009867 | no MR -> candidate analysis |
| Height | 5e-125 | rs9385404 | 6 | GCST90245848 | MR: beta=0.0178, p=0.0979 (cis) |
| A body shape index | 8e-122 | rs72959041 | 20 | GCST90020024 | no MR -> candidate analysis |
| …and 728 more traits (see JSON) |
Top diseases by Open Targets association (of 331 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 | 0.822 | — | common-variant locus | no MR -> candidate analysis |
| bone fracture | 0.819 | — | common-variant locus | no MR -> candidate analysis |
| type 2 diabetes mellitus | 0.788 | — | common-variant locus | no MR -> candidate analysis |
| osteoporosis | 0.794 | — | common-variant locus | MR: beta=-0.231, p=0.0112 (cis) |
| metabolic syndrome | 0.762 | — | common-variant locus | no MR -> candidate analysis |
| smoking behavior | 0.76 | — | common-variant locus | no MR -> candidate analysis |
| endometriosis | 0.724 | — | common-variant locus | no MR -> candidate analysis |
| upper extremity fracture | 0.736 | — | common-variant locus | no MR -> candidate analysis |
| bone disorder | 0.733 | — | common-variant locus | MR: beta=-0.741, p=0.167 (cis) |
| Varicose veins | 0.716 | — | common-variant locus | MR: beta=-0.405, p=1.80e-05 (cis) |
| diabetes mellitus | 0.708 | — | common-variant locus | no MR -> candidate analysis |
| alcohol drinking | 0.713 | — | common-variant locus | no MR -> candidate analysis |
| Crohn disease | 0.693 | — | common-variant locus | no MR -> candidate analysis |
| uterine corpus leiomyoma | 0.674 | — | common-variant locus | no MR -> candidate analysis |
| metabolic dysfunction-associated steatotic liver disease | 0.663 | — | common-variant locus | no MR -> candidate analysis |
Of the 15 rows above, 12 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 | 1 known modulators (RSPO3-LGR4) |
| gnomAD constraint | pLI=0.035, LOEUF=0.699 — LoF-tolerant |
| GWAS Catalog | 268 unique SNPs / 613 rows |
| ClinVar | 60 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 331 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 ‘RSPO3’ and resolved to ‘RSPO3-LGR4’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 60 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 740 traits by best p-value, aggregated from 1770 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/Q9BXY4 — 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/ENSG00000146374/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4665590/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/RSPO3 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/RSPO3 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=RSPO3%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/RSPO3 — GWAS Catalog search API (live; release not exposed)