CausalSentinel

Protein Dossier — ENDOU (Uridylate-specific endoribonuclease)

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
Cough on most days 0.302 0.0612 8.37e-07 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma -0.187 0.0544 5.75e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: K35 Acute appendicitis 0.487 0.145 7.91e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0641 0.0257 0.0125 Wald ratio 1 cis NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.887 0.365 0.0152 Wald ratio 1 cis NA
Squamous cell lung cancer 0.484 0.2 0.0157 Wald ratio 1 cis NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone 0.322 0.134 0.0163 Wald ratio 1 cis NA
Non-cancer illness code self-reported: ankylosing spondylitis 0.462 0.201 0.0214 Wald ratio 1 cis NA
Lung cancer 0.257 0.126 0.041 Wald ratio 1 cis NA
Neuroticism -0.0491 0.0245 0.0455 Wald ratio 1 cis NA
Eye problems or disorders: Cataract -0.22 0.111 0.0471 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.29 0.147 0.0477 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

4 association rows across 4 traits (3 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
Poly(U)-specific endoribonuclease levels 4e-37 rs11830795 1 GCST90426432 no MR -> candidate analysis
ENDOU protein levels 8e-26 rs2238145 1 GCST90469107 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 3e-24 rs7969186 1 GCST90838669 no MR -> candidate analysis
Dementia 6e-6 rs1234820 1 GCST90449024 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 368 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
basal cell carcinoma 0.312 common-variant locus MR: beta=0.198, p=0.158 (cis)
cardiovascular disorder 0.197 common-variant locus no MR -> candidate analysis
kidney disorder 0.118 common-variant locus no MR -> candidate analysis
lung cancer 0.108 common-variant locus MR: beta=0.484, p=0.0157 (cis)

Of the 4 rows above, 2 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=1.3e-15, LOEUF=1.15 — LoF-tolerant
GWAS Catalog 74 unique SNPs / 148 rows
ClinVar 74 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance