CausalSentinel

Protein Dossier — CTRB1 (Chymotrypsinogen B)

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
Inflammatory bowel disease -0.0737 0.0182 4.96e-05 Wald ratio 1 cis NA
Crohn’s disease -0.0871 0.0219 7.12e-05 Wald ratio 1 cis NA
Amyotrophic lateral sclerosis -0.103 0.0311 8.89e-04 Wald ratio 1 cis NA
Birth weight -0.0199 0.00634 0.00165 Wald ratio 1 cis NA
Body mass index (BMI) -0.0118 0.00413 0.00415 Wald ratio 1 cis NA
Ulcerative colitis -0.0641 0.0227 0.00477 Wald ratio 1 cis NA
Non-cancer illness code self-reported: iron deficiency anaemia -0.181 0.0682 0.00805 Wald ratio 1 cis NA
Ischemic stroke -0.0697 0.0283 0.0137 Wald ratio 1 cis NA
Multiple sclerosis -0.0695 0.0286 0.0152 Wald ratio 1 cis NA
Femoral neck bone mineral density 0.0306 0.0129 0.018 Wald ratio 1 cis NA
Small vessel disease -0.143 0.0618 0.0208 Wald ratio 1 cis NA
HDL cholesterol -0.0195 0.0085 0.022 Wald ratio 1 cis NA
…and 107 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

78 association rows across 55 traits (72 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
Chymotrypsinogen B2 levels 9e-1119 rs66584288 2 GCST90247030 no MR -> candidate analysis
Chymotrypsinogen B levels 1e-252 rs8051363 2 GCST90247029 no MR -> candidate analysis
Blood protein levels 6e-235 rs7202566 4 GCST006585 no MR -> candidate analysis
CTRL protein levels 7e-202 rs8051363 2 GCST90468907 no MR -> candidate analysis
CPB1/KIRREL2 protein level ratio 8e-184 rs7202877 1 GCST90314210 no MR -> candidate analysis
Serum levels of protein CTRB2 1e-159 rs8051363 1 GCST90089138 no MR -> candidate analysis
Chymotrypsinogen B levels (CTRB1.5671.1.3) 2e-157 rs8051363 2 GCST90240705 no MR -> candidate analysis
Circulating CPA1 levels 5e-139 rs8055167 1 GCST90859969 no MR -> candidate analysis
Circulating CPB1 levels 1e-120 rs8055167 1 GCST90859977 no MR -> candidate analysis
CELA3A/KIRREL2 protein level ratio 5e-104 rs7202877 1 GCST90314013 no MR -> candidate analysis
CTRC/KIRREL2 protein level ratio 2e-96 rs7202877 1 GCST90314309 no MR -> candidate analysis
Circulating PRSS2 levels 6e-94 rs8055167 1 GCST90860437 no MR -> candidate analysis
…and 43 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 62 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
type 2 diabetes mellitus 0.95 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.933 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.896 common-variant locus no MR -> candidate analysis
type 1 diabetes mellitus 0.855 common-variant locus no MR -> candidate analysis
age-related macular degeneration 0.771 common-variant locus no MR -> candidate analysis
COVID-19 0.739 common-variant locus no MR -> candidate analysis
diabetic neuropathy 0.724 common-variant locus no MR -> candidate analysis
exocrine pancreatic carcinoma 0.704 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.68 common-variant locus no MR -> candidate analysis
alcoholic pancreatitis 0.59 common-variant locus no MR -> candidate analysis
acute pancreatitis 0.529 common-variant locus no MR -> candidate analysis
atrophic macular degeneration 0.514 common-variant locus no MR -> candidate analysis
wet macular degeneration 0.514 common-variant locus no MR -> candidate analysis
coronary atherosclerosis 0.465 common-variant locus no MR -> candidate analysis
Abnormal pupillary function 0.453 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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 (Chymotrypsinogen B)
gnomAD constraint pLI=0.00012, LOEUF=1.13 — LoF-tolerant
GWAS Catalog 116 unique SNPs / 285 rows
ClinVar 117 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 2 drugs

Caveats declared by the tools

Sources

Provenance