CausalSentinel

Protein Dossier — SFRP4 (Secreted frizzled-related protein 4)

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
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] 0.288 0.075 1.24e-04 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0557 0.0155 3.10e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.392 0.121 0.00125 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0272 0.00979 0.00552 Wald ratio 1 cis NA
Potassium in urine -0.0326 0.0121 0.00714 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine -0.027 0.0114 0.0178 Wald ratio 1 cis NA
Cough on most days -0.173 0.0734 0.0182 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.184 0.0836 0.0281 Wald ratio 1 cis NA
Fractured or broken bones in last 5 years -0.0887 0.0407 0.0295 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0423 0.0197 0.0322 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities -0.219 0.105 0.037 Wald ratio 1 cis NA
Diagnoses - main ICD10: K43 Ventral hernia 0.284 0.138 0.0396 Wald ratio 1 cis NA
…and 67 more outcomes (see JSON)              

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

373 association rows across 88 traits (356 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
Height 2e-277 rs6963134 25 GCST90245848 no MR -> candidate analysis
Estimated bone mineral density 2e-229 rs10235021 6 GCST90726625 no MR -> candidate analysis
Heel bone mineral density 2e-215 rs6973667 27 GCST007066 MR: beta=0.0557, p=3.10e-04 (cis)
Dupuytren’s disease 2e-176 rs2044830 9 GCST90301252 no MR -> candidate analysis
SFRP4 protein levels 3e-175 rs75207237 2 GCST90470611 no MR -> candidate analysis
Contracture of palmar fascia [Dupuytren’s disease] (PheCode 5e-143 rs74335252 2 GCST90480521 no MR -> candidate analysis
Secreted frizzled-related protein 4 levels 5e-50 rs75207237 2 GCST90249517 no MR -> candidate analysis
Bone density (confirmatory factor analysis Factor 19) 1e-41 rs939666 1 GCST90309353 no MR -> candidate analysis
Standing height (UKB data field 50) 3e-38 rs1403987 1 GCST90468178 no MR -> candidate analysis
Lumbar spine bone mineral density 4e-38 rs6959212 2 GCST001482 MR: beta=0.0378, p=0.401 (cis)
Height (baseline) 1e-34 rs1524065 9 GCST90565843 no MR -> candidate analysis
Fasciitis (PheCode 728.7) 5e-32 rs6965376 2 GCST90476244 no MR -> candidate analysis
…and 76 more traits (see JSON)          

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 691 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
Pyle disease 0.792 established (curated) no MR -> candidate analysis

Of the 1 rows above, 1 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=1.7e-06, LOEUF=0.963 — LoF-tolerant
GWAS Catalog 211 unique SNPs / 388 rows
ClinVar 202 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance