CausalSentinel

Protein Dossier — CLPS (Colipase)

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: joint disorder 0.204 0.0676 0.0025 Wald ratio 1 cis NA
Clear cell ovarian cancer 0.261 0.0926 0.00492 Wald ratio 1 cis NA
Non-cancer illness code self-reported: arthritis (nos) 0.138 0.0568 0.0152 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vitiligo 0.516 0.216 0.0166 Wald ratio 1 cis NA
Potassium in urine -0.0135 0.00573 0.0185 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine -0.0115 0.00541 0.0341 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.121 0.0598 0.0422 Wald ratio 1 cis NA
Rheumatoid arthritis -0.0681 0.0353 0.0536 Wald ratio 1 cis NA
Femoral neck bone mineral density 0.0331 0.0173 0.0557 Wald ratio 1 cis NA
Weight -0.00941 0.00499 0.0593 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma -0.0966 0.0521 0.0634 Wald ratio 1 cis NA
Diagnoses - main ICD10: K80 Cholelithiasis 0.0655 0.0369 0.0755 Wald ratio 1 cis NA
…and 57 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

12 association rows across 9 traits (11 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
CLPS protein levels 9e-296 rs116063149 2 GCST90468786 no MR -> candidate analysis
Serum levels of protein CLPS 1e-141 rs2766598 2 GCST90089194 no MR -> candidate analysis
Colipase levels 9e-129 rs9470101 2 GCST90247108 no MR -> candidate analysis
Colipase levels (CLPS.5749.53.3) 5e-43 rs2766594 1 GCST90240742 no MR -> candidate analysis
Height (baseline) 1e-18 rs6906260 1 GCST90565843 no MR -> candidate analysis
SEMA3G protein levels 6e-12 rs148028295 1 GCST90470571 no MR -> candidate analysis
Physical function (baseline) 1e-10 rs6906260 1 GCST90565837 no MR -> candidate analysis
Phospholipid levels in large HDL 4e-8 rs3748048 1 GCST90092852 no MR -> candidate analysis
Spondylolisthesis 3e-7 rs140407801 1 GCST90104232 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 413 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
celiac disease 0.219 common-variant locus no MR -> candidate analysis
dermatitis herpetiformis 0.156 common-variant locus no MR -> candidate analysis
hypothyroidism 0.13 common-variant locus MR: beta=0.0191, p=0.438 (cis)
myxedema 0.13 common-variant locus no MR -> candidate analysis

Of the 4 rows above, 3 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 (E3 ubiquitin-protein ligase UBR1)
gnomAD constraint pLI=0.0022, LOEUF=1.56 — LoF-tolerant
GWAS Catalog 95 unique SNPs / 190 rows
ClinVar 26 records; 7 pathogenic in sample of 26
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance