CausalSentinel

Protein Dossier — GLCE (D-glucuronyl C5-epimerase)

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 -0.0272 0.00962 0.0047 Wald ratio 1 cis NA
Squamous cell lung cancer 0.0991 0.0361 0.00602 Wald ratio 1 cis NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.116 0.0429 0.00686 Wald ratio 1 cis NA
Alcohol intake frequency -0.0123 0.00512 0.0164 Wald ratio 1 cis NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia -0.0708 0.0298 0.0173 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] -0.0627 0.0265 0.0182 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine -0.0458 0.0209 0.0286 Wald ratio 1 cis NA
Non-cancer illness code self-reported: ankylosing spondylitis -0.161 0.0774 0.0371 Wald ratio 1 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.0435 0.0213 0.0411 Wald ratio 1 cis NA
Subjective well being 0.00965 0.00483 0.0455 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated -0.0089 0.00448 0.047 Wald ratio 1 cis NA
Schizophrenia 0.03 0.0152 0.0482 Wald ratio 1 cis NA
…and 108 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

20 association rows across 16 traits (14 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
D-glucuronyl C5-epimerase levels 1e-693 rs35810867 3 GCST90247272 no MR -> candidate analysis
D-glucuronyl C5-epimerase levels (GLCE.7808.5.3) 8e-245 rs11854180 1 GCST90240871 no MR -> candidate analysis
Blood protein levels 2e-229 rs3865014 1 GCST006585 no MR -> candidate analysis
D-glucuronyl C5-epimerase level in Chronic kidney disease wi 8e-85 rs3865014 1 GCST90238640 no MR -> candidate analysis
systolic blood pressure (SBP, maximum, inv-normal transforme 6e-12 rs11629932 1 GCST90480705 no MR -> candidate analysis
Medication use for hypertension (number of purchases) 1e-11 rs199641012 1 GCST90250905 no MR -> candidate analysis
ER membrane protein complex subunit 1 protein levels (SomaSc 2e-11 rs3865014 1 GCST90437733 no MR -> candidate analysis
Smoking initiation 2e-9 rs2899748 1 GCST90243985 no MR -> candidate analysis
Mean corpuscular hemoglobin 2e-9 rs148377198 3 GCST007068 no MR -> candidate analysis
Peak expiratory flow 4e-9 rs71147591 1 GCST90270085 no MR -> candidate analysis
Empathy quotient 7e-7 rs201219357 1 GCST005751 no MR -> candidate analysis
R-6-hydroxywarfarin levels 1e-6 rs149533198 1 GCST90129566 no MR -> candidate analysis
…and 4 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 2390 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 0.437 common-variant locus no MR -> candidate analysis
inherited hemoglobinopathy 0.397 common-variant locus no MR -> candidate analysis
smoking initiation 0.36 common-variant locus no MR -> candidate analysis
inherited retinal dystrophy 0.353 common-variant locus no MR -> candidate analysis
septic shock 0.158 common-variant locus no MR -> candidate analysis

Of the 5 rows above, 5 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=0.48, LOEUF=0.582 — LoF-tolerant
GWAS Catalog 33 unique SNPs / 66 rows
ClinVar 76 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance