CausalSentinel

Protein Dossier — RRM1 (Ribonucleoside-diphosphate reductase large subunit)

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
Mean cell haemoglobin 0.166 0.0231 6.88e-13 Wald ratio 1 trans NA
Mean cell volume 0.381 0.059 1.05e-10 Wald ratio 1 trans NA
Fasting glucose -0.0231 0.00714 0.00122 Wald ratio 1 trans NA
Systemic lupus erythematosus -0.348 0.109 0.00135 Wald ratio 1 trans NA
Haemoglobin concentration 0.038 0.0132 0.00407 Wald ratio 1 trans NA
Body mass index (BMI) -0.0159 0.00566 0.00499 Wald ratio 1 trans NA
Weight -0.014 0.005 0.00513 Wald ratio 1 trans NA
Depressive symptoms -0.0231 0.0084 0.00596 Wald ratio 1 trans NA
Red blood cell count -0.0136 0.00504 0.00676 Wald ratio 1 trans NA
Non-cancer illness code self-reported: anxiety or panic attacks -0.152 0.057 0.00775 Wald ratio 1 trans NA
Mean cell haemoglobin concentration 0.0206 0.00819 0.012 Wald ratio 1 trans NA
Cancer code self-reported: prostate cancer 0.133 0.0582 0.0219 Wald ratio 1 trans NA
…and 96 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

37 association rows across 20 traits (33 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
Mean corpuscular volume 9e-65 rs67074167 6 GCST90002338 no MR -> candidate analysis
Mean corpuscular hemoglobin 2e-51 rs725518 7 GCST90002326 no MR -> candidate analysis
Mean corpuscular volume (UKB data field 30040) 1e-43 rs11030967 1 GCST90468086 no MR -> candidate analysis
Mean corpuscular haemoglobin (UKB data field 30050) 8e-39 rs11030967 1 GCST90468084 no MR -> candidate analysis
Mean reticulocyte volume 2e-27 rs725518 1 GCST90002396 no MR -> candidate analysis
Mean reticulocyte volume (UKB data field 30260) 1e-24 rs11030976 1 GCST90468088 no MR -> candidate analysis
Mean spheric corpuscular volume 2e-24 rs725518 2 GCST90002397 no MR -> candidate analysis
Red cell distribution width 3e-23 rs232054 5 GCST90002369 no MR -> candidate analysis
Mitochondrial DNA copy number (adjusted) 1e-19 rs12806698 1 GCST90268497 no MR -> candidate analysis
Mean sphered cell volume (UKB data field 30270) 6e-19 rs11030976 1 GCST90468089 no MR -> candidate analysis
Mitochondrial DNA copy number (raw) 4e-17 rs12806698 1 GCST90268498 no MR -> candidate analysis
mean platelet volume (MPV, minimum, inv-norm transformed) 8e-15 rs10835611 1 GCST90479709 no MR -> candidate analysis
…and 8 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 458 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
progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6 0.657 established (curated) no MR -> candidate analysis

Of the 1 rows above, 1 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 (Ribonucleoside-diphosphate reductase large subunit)
gnomAD constraint pLI=1, LOEUF=0.275 — LoF-INTOLERANT
GWAS Catalog 42 unique SNPs / 84 rows
ClinVar 110 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx 13 clinical annotations across 5 drugs

Caveats declared by the tools

Sources

Provenance