CausalSentinel

Protein Dossier — UROS (Uroporphyrinogen-III synthase)

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
Thalamus volume -90.1 34.9 0.00994 Wald ratio 1 cis NA
Diagnoses - main ICD10: R14 Flatulence and related conditions 0.716 0.289 0.0133 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pneumothorax 0.784 0.326 0.016 Wald ratio 1 cis NA
Anorexia nervosa 0.394 0.167 0.0186 Wald ratio 1 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.161 0.0709 0.0229 Wald ratio 1 cis NA
Endometrioid ovarian cancer -0.348 0.156 0.0258 Wald ratio 1 cis NA
Type 2 diabetes -0.37 0.17 0.0299 Wald ratio 1 cis NA
Nucleus accumbens volume -13.2 6.1 0.0308 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0451 0.021 0.0318 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bladder problem (not cancer) 0.275 0.131 0.0359 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0339 0.0167 0.0424 Wald ratio 1 cis NA
Diagnoses - main ICD10: K35 Acute appendicitis 0.287 0.142 0.0437 Wald ratio 1 cis NA
…and 68 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

6 association rows across 6 traits (5 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
UROS protein levels 3e-60 rs10794023 1 GCST90471017 no MR -> candidate analysis
Uroporphyrinogen-III synthase levels 4e-53 rs1935451 1 GCST90250109 no MR -> candidate analysis
Serum levels of protein UROS 1e-47 rs2027515 1 GCST90086638 no MR -> candidate analysis
Blood protein levels 4e-27 rs2027515 1 GCST006585 no MR -> candidate analysis
Brain morphology (MOSTest) 2e-8 rs41315014 1 GCST90239729 no MR -> candidate analysis
Appendicular lean mass 5e-8 rs10901430 1 GCST009577 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 758 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
Congenital erythropoietic porphyria 0.898 established (curated) no MR -> candidate analysis
cutaneous porphyria 0.916 established (curated) no MR -> candidate analysis
hereditary disease 0.313 established (curated) no MR -> candidate analysis

Of the 3 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 (Uroporphyrinogen-III synthase)
gnomAD constraint pLI=0.0019, LOEUF=0.809 — LoF-tolerant
GWAS Catalog 21 unique SNPs / 42 rows
ClinVar 241 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance