CausalSentinel

Protein Dossier — RPIA (Ribose-5-phosphate isomerase)

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
Diagnoses - main ICD10: N81 Female genital prolapse 0.306 0.0908 7.60e-04 Wald ratio 1 trans NA
Hirschsprung’s disease -1.12 0.406 0.00557 Wald ratio 1 trans NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.229 0.0955 0.0164 Wald ratio 1 trans NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.347 0.147 0.0185 Wald ratio 1 trans NA
Non-cancer illness code self-reported: arthritis (nos) 0.297 0.127 0.0199 Wald ratio 1 trans NA
Diagnoses - main ICD10: K43 Ventral hernia 0.327 0.163 0.0447 Wald ratio 1 trans NA
Diagnoses - main ICD10: R14 Flatulence and related conditions 0.685 0.353 0.0524 Wald ratio 1 trans NA
Fractured or broken bones in last 5 years 0.0798 0.0421 0.0584 Wald ratio 1 trans NA
Non-cancer illness code self-reported: high cholesterol -0.0804 0.0429 0.0609 Wald ratio 1 trans NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis 0.191 0.106 0.0716 Wald ratio 1 trans NA
Fractured bone site(s): Other bones 0.101 0.0576 0.0792 Wald ratio 1 trans NA
Neuroticism 0.0459 0.0266 0.0841 Wald ratio 1 trans NA
…and 45 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

7 association rows across 7 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
LRRTM2 protein levels 1e-8 rs10183742 1 GCST90453017 no MR -> candidate analysis
Protein quantitative trait loci (liver) 3e-8 rs79140613 1 GCST011427 no MR -> candidate analysis
Circulating OPTC levels 4e-8 rs75197437 1 GCST90860578 no MR -> candidate analysis
Colonoscopy-negative controls vs population controls 2e-6 rs34965331 1 GCST005147 no MR -> candidate analysis
COVID-19 (severe vs population) x cardiometabolic health sta 2e-6 rs192911167 1 GCST90102532 no MR -> candidate analysis
Acesulfame levels in elite athletes 6e-6 rs1165703 1 GCST90134191 no MR -> candidate analysis
COVID-19 (severe vs population) x cardiometabolic health sta 6e-6 rs192911167 1 GCST90102531 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 147 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
ribose-5-P isomerase deficiency 0.797 established (curated) no MR -> candidate analysis
hereditary disease 0.68 established (curated) no MR -> candidate analysis
non-melanoma skin carcinoma 0.381 common-variant locus no MR -> candidate analysis
Hashimoto thyroiditis 0.338 common-variant locus no MR -> candidate analysis
autoimmune disease 0.334 common-variant locus no MR -> candidate analysis
skin neoplasm 0.325 common-variant locus no MR -> candidate analysis
hypothyroidism 0.307 common-variant locus no MR -> candidate analysis
immune system disorder 0.29 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.262 common-variant locus no MR -> candidate analysis
skin cancer 0.225 common-variant locus no MR -> candidate analysis
sarcoidosis 0.194 common-variant locus no MR -> candidate analysis
basal cell carcinoma 0.168 common-variant locus no MR -> candidate analysis
respiratory system disorder 0.145 common-variant locus no MR -> candidate analysis
skin disorder 0.145 common-variant locus no MR -> candidate analysis
thyroid gland disorder 0.127 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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 (Ribose-5-phosphate isomerase)
gnomAD constraint pLI=2.5e-08, LOEUF=1.05 — LoF-tolerant
GWAS Catalog 46 unique SNPs / 92 rows
ClinVar 171 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance