CausalSentinel

Protein Dossier — CBLN4 (Cerebellin-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
Weight 0.0654 0.0123 1.05e-07 Wald ratio 1 cis 0.807
Body mass index (BMI) 0.0587 0.0139 2.49e-05 Wald ratio 1 cis NA
HDL cholesterol 0.073 0.0198 2.18e-04 Wald ratio 1 cis NA
Haemoglobin concentration 0.101 0.0326 0.00204 Wald ratio 1 cis NA
Major depressive disorder -0.367 0.124 0.00319 Wald ratio 1 cis NA
Depressive symptoms -0.0505 0.0184 0.00596 Wald ratio 1 cis NA
Triglycerides -0.0524 0.0193 0.00664 Wald ratio 1 cis NA
Neuroblastoma -0.661 0.249 0.00806 Wald ratio 1 cis NA
Non-cancer illness code self-reported: sleep apnoea 0.396 0.175 0.0241 Wald ratio 1 cis NA
Iron 0.126 0.056 0.0242 Wald ratio 1 cis NA
Urinary albumin-to-creatinine ratio 0.0735 0.034 0.0306 Wald ratio 1 cis NA
Red blood cell count 0.0266 0.0124 0.0317 Wald ratio 1 cis NA
…and 105 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

96 association rows across 61 traits (66 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
Bone mineral density mean 1e-300 rs6024398 2 GCST90321120 no MR -> candidate analysis
CBLN4 protein levels 3e-151 rs12624596 10 GCST90468554 no MR -> candidate analysis
Cerebellin-4 levels 9e-41 rs6024420 3 GCST90246872 no MR -> candidate analysis
Weight 1e-23 rs6098825 3 GCST90662910 MR: beta=0.0654, p=1.05e-07 (cis)
Serum levels of protein CBLN4 3e-23 rs8119592 2 GCST90089146 no MR -> candidate analysis
Adolescent idiopathic scoliosis 2e-21 rs6069391 1 GCST006287 no MR -> candidate analysis
Smoking initiation 7e-18 rs6069426 3 GCST90243985 no MR -> candidate analysis
Weight (mean, inv-normal transformed) 7e-17 rs6024462 1 GCST90480727 no MR -> candidate analysis
Weight (maximum, inv-normal transformed) 3e-16 rs6024462 1 GCST90480726 no MR -> candidate analysis
Body mass index (BMI, mean, inv-normal transformed) 6e-16 rs6024462 1 GCST90479522 no MR -> candidate analysis
Weight (minimum, inv-normal transformed) 6e-16 rs6024462 1 GCST90480728 no MR -> candidate analysis
Body size at age 10 8e-16 rs2207894 1 GCST010989 no MR -> candidate analysis
…and 49 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 69 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
Abnormality of the skeletal system 0.65 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.597 common-variant locus no MR -> candidate analysis
smoking initiation 0.537 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.499 common-variant locus no MR -> candidate analysis
subarachnoid hemorrhage 0.44 common-variant locus no MR -> candidate analysis
insomnia 0.39 common-variant locus no MR -> candidate analysis
motion sickness 0.372 common-variant locus no MR -> candidate analysis
alcohol drinking 0.363 common-variant locus no MR -> candidate analysis
urolithiasis 0.363 common-variant locus no MR -> candidate analysis
arthropathy 0.355 common-variant locus no MR -> candidate analysis
morbid obesity 0.351 common-variant locus no MR -> candidate analysis
pituitary gland disorder 0.351 common-variant locus no MR -> candidate analysis
diabetic neuropathy 0.349 common-variant locus no MR -> candidate analysis
adolescent idiopathic scoliosis 0.346 common-variant locus no MR -> candidate analysis
Abnormal pupillary function 0.301 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=0.14, LOEUF=0.88 — LoF-tolerant
GWAS Catalog 117 unique SNPs / 162 rows
ClinVar 29 records; 11 pathogenic in sample of 29
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance