CausalSentinel

Protein Dossier — CBR3 (Carbonyl reductase [NADPH] 3)

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
Schizophrenia -0.0503 0.0143 4.26e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis 0.0369 0.0106 4.81e-04 Wald ratio 1 cis NA
Packed cell volume 0.076 0.024 0.0015 Wald ratio 1 cis NA
Diagnoses - main ICD10: M23 Internal derangement of knee 0.0589 0.0208 0.00458 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0153 0.0055 0.00539 Wald ratio 1 cis NA
Systemic lupus erythematosus 0.171 0.063 0.00659 Wald ratio 1 cis NA
Knee and hip osteoarthritis -0.0763 0.0285 0.00745 Wald ratio 1 cis NA
Height -0.00982 0.00406 0.0155 Wald ratio 1 cis NA
Thalamus volume 20.2 8.39 0.0158 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine -0.0561 0.0244 0.0216 Wald ratio 1 cis NA
Nucleus accumbens volume 3.23 1.45 0.0257 Wald ratio 1 cis NA
PGC cross-disorder traits -0.0361 0.0164 0.0272 Wald ratio 1 cis NA
…and 115 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

33 association rows across 21 traits (27 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
Carbonyl reductase [NADPH] 3 levels 4e-387 rs60043102 3 GCST90246885 no MR -> candidate analysis
Serum levels of protein CBR3 6e-286 rs12483755 2 GCST90087775 no MR -> candidate analysis
Carbonyl reductase [NADPH] 3 levels (CBR3.14091.42.3) 3e-259 rs1028997 3 GCST90240594 no MR -> candidate analysis
Blood protein levels 3e-160 rs60409141 1 GCST006585 no MR -> candidate analysis
Height 5e-48 rs8133052 3 GCST90245848 MR: beta=-0.00982, p=0.0155 (cis)
Insulin-like growth factor 1 levels 2e-42 rs9636630 2 GCST90019511 no MR -> candidate analysis
Cerebrospinal fluid protein CBR3 levels 8e-39 rs1056892 1 GCST90940678 no MR -> candidate analysis
Carbonyl reductase [NADPH] 3 level in Chronic kidney disease 4e-24 rs7283498 1 GCST90234182 no MR -> candidate analysis
C-reactive protein levels 2e-12 rs7280982 1 GCST009777 no MR -> candidate analysis
Prostate cancer 8e-12 rs2242798 2 GCST90274713 MR: beta=-0.0599, p=0.142 (cis)
Free Cholesterol to Total Lipids in Very Large VLDL percenta 1e-10 rs113357683 1 GCST90501311 no MR -> candidate analysis
GH3 domain-containing protein protein levels (SomaScan ID:14 2e-9 rs1028997 1 GCST90439593 no MR -> candidate analysis
…and 9 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 123 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
prostate carcinoma 0.561 common-variant locus no MR -> candidate analysis
escherichia coli infection 0.544 common-variant locus no MR -> candidate analysis
frozen shoulder 0.355 common-variant locus no MR -> candidate analysis
facial morphology 0.099 common-variant locus no MR -> candidate analysis
Burkitt lymphoma 0.092 common-variant locus no MR -> candidate analysis
femoral neck fracture 0.081 common-variant locus no MR -> candidate analysis
stomach disorder 0.065 common-variant locus no MR -> candidate analysis
alcohol drinking 0.053 common-variant locus no MR -> candidate analysis
Left bundle branch block 0.046 common-variant locus no MR -> candidate analysis

Of the 9 rows above, 9 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 (Carbonyl reductase [NADPH] 3)
gnomAD constraint pLI=2.8e-06, LOEUF=1.88 — LoF-tolerant
GWAS Catalog 53 unique SNPs / 112 rows
ClinVar 127 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx 4 clinical annotations across 5 drugs

Caveats declared by the tools

Sources

Provenance