CausalSentinel

Protein Dossier — RRM2B (Ribonucleoside-diphosphate reductase subunit M2 B)

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: gastro-oesophageal reflux (gord) or gastric reflux 0.183 0.0605 0.0025 Wald ratio 1 cis NA
Microalbuminuria -0.4 0.132 0.0025 Wald ratio 1 cis NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.31 0.106 0.00339 Wald ratio 1 cis NA
Neo-agreeableness 0.879 0.325 0.00681 Wald ratio 1 cis NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis 0.279 0.109 0.0106 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.171 0.0673 0.011 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.146 0.0579 0.0119 Wald ratio 1 cis NA
Fractured bone site(s): Wrist -0.364 0.159 0.0221 Wald ratio 1 cis NA
Urate -0.0676 0.0307 0.0278 Wald ratio 1 cis NA
Fractured or broken bones in last 5 years -0.116 0.0528 0.0279 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes -0.0598 0.0276 0.0301 Wald ratio 1 cis NA
Vascular or heart problems diagnosed by doctor: Angina -0.232 0.108 0.0312 Wald ratio 1 cis NA
…and 97 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

25 association rows across 18 traits (21 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
GFER/RRM2B protein level ratio 4e-115 rs11784180 1 GCST90314920 no MR -> candidate analysis
RRM2B/SUGT1 protein level ratio 2e-103 rs11784180 1 GCST90315789 no MR -> candidate analysis
RRM2B/SMAD1 protein level ratio 7e-90 rs11784180 1 GCST90315788 no MR -> candidate analysis
Ribonucleoside-diphosphate reductase subunit M2 B levels 4e-77 rs16869295 2 GCST90249272 no MR -> candidate analysis
Circulating RRM2B levels 2e-54 rs1037699 2 GCST90860320 no MR -> candidate analysis
Serum levels of protein RRM2B 7e-46 rs78020802 2 GCST90090386 no MR -> candidate analysis
Blood protein levels 7e-31 rs28928597 2 GCST006585 no MR -> candidate analysis
Mean corpuscular volume 3e-15 rs2290707 1 GCST006011 no MR -> candidate analysis
Ribonucleoside-diphosphate reductase subunit M2 B (analyte X 2e-13 rs11778107 1 GCST90427546 no MR -> candidate analysis
Red blood cell count 2e-12 rs28999676 3 GCST90002363 MR: beta=-0.0163, p=0.218 (cis)
Mean corpuscular hemoglobin 5e-12 rs2290707 2 GCST90018744 no MR -> candidate analysis
Ribonucleoside-diphosphate reductase subunit M2 B levels (RR 1e-11 rs74589258 1 GCST90242672 no MR -> candidate analysis
…and 6 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 1451 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
mitochondrial DNA depletion syndrome 8a 0.938 established (curated) no MR -> candidate analysis
Mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy 0.868 established (curated) no MR -> candidate analysis
mitochondrial dna depletion syndrome 8b (mngie type) 0.745 established (curated) no MR -> candidate analysis
progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 0.902 established (curated) no MR -> candidate analysis
rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction 0.827 established (curated) no MR -> candidate analysis
mitochondrial DNA depletion syndrome, encephalomyopathic form 0.608 established (curated) no MR -> candidate analysis
autosomal dominant progressive external ophthalmoplegia 0.608 established (curated) no MR -> candidate analysis
mitochondrial neurogastrointestinal encephalomyopathy 0.76 established (curated) no MR -> candidate analysis
adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy 0.608 established (curated) no MR -> candidate analysis
mitochondrial disease 0.684 established (curated) no MR -> candidate analysis

Of the 10 rows above, 10 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 1 known modulators (Ribonucleotide reductase)
gnomAD constraint pLI=0.09, LOEUF=0.634 — LoF-tolerant
GWAS Catalog 37 unique SNPs / 74 rows
ClinVar 516 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 2 drugs

Caveats declared by the tools

Sources

Provenance