CausalSentinel

Protein Dossier — CDH13 (Cadherin-13)

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
Non-cancer illness code self-reported: high cholesterol -0.182 0.038 1.72e-06 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) 0.0393 0.0101 1.04e-04 Wald ratio 1 trans NA
Forced vital capacity (FVC) 0.0342 0.00959 3.57e-04 Wald ratio 1 trans NA
Systolic blood pressure automated reading -0.0393 0.012 0.00102 Wald ratio 1 trans NA
Body mass index (BMI) -0.0345 0.0117 0.00313 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension -0.0526 0.021 0.0123 Wald ratio 1 trans NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain -0.168 0.0671 0.0125 Wald ratio 1 trans NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.219 0.0898 0.0148 Wald ratio 1 trans NA
Bulimia nervosa -0.0817 0.0337 0.0152 Wald ratio 1 trans NA
Endometrioid ovarian cancer -0.349 0.145 0.0158 Wald ratio 1 trans NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis -0.325 0.144 0.0236 Wald ratio 1 trans NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast -0.269 0.122 0.027 Wald ratio 1 trans NA
…and 65 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

524 association rows across 276 traits (344 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
HSBP1 protein levels 5e-307 rs692603 29 GCST90469481 no MR -> candidate analysis
Bone mineral density mean 1e-300 rs758925805 6 GCST90321120 no MR -> candidate analysis
Adiponectin levels 6e-270 rs12051272 13 GCST90662862 no MR -> candidate analysis
BRK1 protein levels 2e-118 rs707236 4 GCST90468469 no MR -> candidate analysis
Adiponectin levels (BMI-adjusted) 2e-68 rs12051272 2 GCST90011881 no MR -> candidate analysis
Pulse pressure 2e-67 rs7500448 14 GCST90310296 no MR -> candidate analysis
ADIPOQ protein levels 7e-39 rs12051272 2 GCST90468245 no MR -> candidate analysis
WASHC3 protein levels 2e-35 rs707236 1 GCST90471069 no MR -> candidate analysis
Core binding factor acute myeloid leukemia 4e-26 rs4782534; rs1489313 2 GCST008413 no MR -> candidate analysis
Coronary atherosclerosis (PheCode 411.4) 7e-25 rs7500448 2 GCST90475936 no MR -> candidate analysis
Educational attainment 8e-25 rs8044562 11 GCST90105038 no MR -> candidate analysis
F-fish liking (derived food-liking factor) 3e-24 rs11859365 1 GCST90094762 no MR -> candidate analysis
…and 264 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 553 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
obesity disorder 0.758 common-variant locus no MR -> candidate analysis
smoking initiation 0.743 common-variant locus no MR -> candidate analysis
placenta praevia 0.694 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.635 common-variant locus no MR -> candidate analysis
Alzheimer disease 0.622 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.603 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.625 common-variant locus MR: beta=0.219, p=0.0148 (trans)
hypertensive disorder 0.609 common-variant locus no MR -> candidate analysis
myocardial ischemia 0.616 common-variant locus no MR -> candidate analysis
coronary atherosclerosis 0.607 common-variant locus no MR -> candidate analysis
substance abuse 0.603 common-variant locus no MR -> candidate analysis
angina pectoris 0.592 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.579 common-variant locus no MR -> candidate analysis
cardiovascular disorder 0.573 common-variant locus no MR -> candidate analysis
alcohol drinking 0.581 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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=0.85, LOEUF=0.529 — LoF-tolerant
GWAS Catalog 252 unique SNPs / 646 rows
ClinVar 326 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance