CausalSentinel

Protein Dossier — CRHBP (Corticotropin-releasing hormone-binding protein)

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
HOMA-B 0.016 0.00724 0.0267 Wald ratio 1 cis NA
Microalbuminuria 0.0978 0.045 0.0297 Wald ratio 1 cis NA
Urinary albumin-to-creatinine ratio 0.0294 0.0135 0.0297 Wald ratio 1 cis NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter -0.107 0.0521 0.0401 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.105 0.0517 0.0431 Wald ratio 1 cis NA
Serum cystatin C (eGFRcys) -0.00763 0.00391 0.0512 Wald ratio 1 cis NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis 0.0812 0.043 0.0592 Wald ratio 1 cis NA
Coronary heart disease 0.0366 0.02 0.0671 Wald ratio 1 cis NA
Sodium in urine -0.00879 0.00485 0.0699 Wald ratio 1 cis NA
Depressive symptoms -0.0176 0.00978 0.0719 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine -0.00831 0.00472 0.0783 Wald ratio 1 cis NA
Putamen volume 21.6 12.3 0.0792 Wald ratio 1 cis NA
…and 86 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

14 association rows across 9 traits (12 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
Hematological traits (multi-trait analysis) 2e-110 rs72763266 1 GCST90838669 no MR -> candidate analysis
Circulating CRHBP levels 1e-84 rs7721799 5 GCST90860650 no MR -> candidate analysis
CRHBP protein levels 2e-35 rs189832182 2 GCST90468860 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 2e-24 rs492287 1 GCST90468087 no MR -> candidate analysis
Corticotropin-releasing factor-binding protein levels 7e-15 rs58714487 1 GCST90247155 no MR -> candidate analysis
Blood cell traits latent factor 5 (platelet) 5e-9 rs7734134 1 GCST90559247 no MR -> candidate analysis
Varicose veins 9e-9 rs247749 1 GCST007225 MR: beta=0.0251, p=0.456 (cis)
Chronotype 1e-7 rs32897 1 GCST007576 no MR -> candidate analysis
Acute graft-versus-host disease (gut) (donor effect) 4e-7 rs1651094 1 GCST90102564 no MR -> candidate analysis

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

Top diseases by Open Targets association (of 140 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
nephritis 0.371 common-variant locus no MR -> candidate analysis
Nephropathy 0.371 common-variant locus no MR -> candidate analysis
Varicose veins 0.118 common-variant locus MR: beta=0.0251, p=0.456 (cis)

Of the 3 rows above, 2 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 0 known modulators (Corticotropin-releasing factor-binding protein)
gnomAD constraint pLI=0.0014, LOEUF=0.8 — LoF-tolerant
GWAS Catalog 47 unique SNPs / 94 rows
ClinVar 41 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance