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 |
|---|---|---|---|---|---|---|---|
| Non-cancer illness code self-reported: chronic obstructive airways disease or copd | 0.419 | 0.163 | 0.0102 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: R35 Polyuria | 0.384 | 0.158 | 0.0147 | Wald ratio | 1 | cis | NA |
| Putamen volume | -83.8 | 35.3 | 0.0177 | Wald ratio | 1 | cis | NA |
| Squamous cell lung cancer | -0.324 | 0.151 | 0.0326 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: polio or poliomyelitis | 0.658 | 0.31 | 0.0339 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level | 0.477 | 0.233 | 0.0405 | Wald ratio | 1 | cis | NA |
| Bulimia nervosa | -0.0814 | 0.0407 | 0.0455 | Wald ratio | 1 | cis | NA |
| Hippocampus volume | 55 | 27.6 | 0.0466 | Wald ratio | 1 | cis | NA |
| Forced expiratory volume in 1-second (FEV1) | 0.024 | 0.0121 | 0.0478 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: N81 Female genital prolapse | 0.193 | 0.0977 | 0.048 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: K57 Diverticular disease of intestine | -0.241 | 0.128 | 0.0598 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: ankylosing spondylitis | 0.356 | 0.194 | 0.067 | Wald ratio | 1 | cis | NA |
| …and 94 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
29 association rows across 25 traits (11 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 RSPO4 | 1e-20 | rs2207321 | 2 | GCST90090206 | no MR -> candidate analysis |
| R-spondin-4 levels | 6e-19 | rs149154047 | 3 | GCST90427401 | no MR -> candidate analysis |
| Blood protein levels | 9e-14 | rs6056847 | 1 | GCST006585 | no MR -> candidate analysis |
| Vertical cup-disc ratio | 4e-10 | rs4816177 | 2 | GCST90129592 | no MR -> candidate analysis |
| Seropositivity for bacteria peptide (agilent_240518) | 1e-8 | rs111540688 | 1 | GCST90294887 | no MR -> candidate analysis |
| Gut microbiome abundance (class Clostridium sensu stricto sp | 2e-8 | rs7263440 | 1 | GCST90568871 | no MR -> candidate analysis |
| Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infec | 3e-8 | rs502716 | 1 | GCST002365 | no MR -> candidate analysis |
| Total PHF-tau (SNP x SNP interaction) | 9e-8 | rs3769176 x rs6086841 | 1 | GCST010340 | no MR -> candidate analysis |
| Height | 1e-7 | rs6086704 | 1 | GCST90245848 | no MR -> candidate analysis |
| Uracil levels | 3e-7 | rs149071029 | 1 | GCST90503898 | no MR -> candidate analysis |
| X-24309 levels | 3e-7 | rs6057055 | 1 | GCST90245747 | no MR -> candidate analysis |
| Logical memory (immediate recall) in Alzheimer’s disease dem | 5e-7 | rs62187521 | 1 | GCST006994 | no MR -> candidate analysis |
| …and 13 more traits (see JSON) |
Top diseases by Open Targets association (of 90 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 |
|---|---|---|---|---|
| nonsyndromic congenital nail disorder 4 | 0.883 | — | established (curated) | no MR -> candidate analysis |
| Anonychia congenita totalis | 0.814 | — | established (curated) | no MR -> candidate analysis |
| Congenital anonychia | 0.865 | — | established (curated) | no MR -> candidate analysis |
| hereditary disease | 0.682 | — | established (curated) | no MR -> candidate analysis |
| Genu valgum | 0.463 | — | common-variant locus | no MR -> candidate analysis |
| Genu varum | 0.463 | — | common-variant locus | no MR -> candidate analysis |
| neoplasm | 0.414 | — | common-variant locus | MR: beta=-0.147, p=0.296 (cis) |
| open-angle glaucoma | 0.438 | — | common-variant locus | no MR -> candidate analysis |
| glaucoma | 0.424 | — | common-variant locus | no MR -> candidate analysis |
| ovarian dysfunction | 0.097 | — | common-variant locus | no MR -> candidate analysis |
| male reproductive organ cancer | 0.05 | — | common-variant locus | no MR -> candidate analysis |
Of the 11 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=4.4e-08, LOEUF=1.31 — LoF-tolerant |
| GWAS Catalog | 46 unique SNPs / 82 rows |
| ClinVar | 144 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 90 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 ‘RSPO4’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 144 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 25 traits by best p-value, aggregated from 29 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/Q2I0M5 — 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/ENSG00000101282/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/RSPO4 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/RSPO4 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=RSPO4%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/RSPO4 — GWAS Catalog search API (live; release not exposed)