CausalSentinel

Protein Dossier — RPN1 (Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit 1)

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
Alzheimer’s disease 0.197 0.0455 1.53e-05 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate 0.0725 0.0287 0.0115 Inverse variance weighted 2 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate 0.0725 0.0287 0.0115 Inverse variance weighted 2 trans NA
Non-cancer illness code self-reported: osteoporosis 0.0517 0.0226 0.022 Inverse variance weighted 2 cis NA
Non-cancer illness code self-reported: osteoporosis 0.0517 0.0226 0.022 Inverse variance weighted 2 trans NA
Microalbuminuria 0.145 0.0638 0.023 Wald ratio 1 cis NA
Platelet count 2.55 1.2 0.0335 Wald ratio 1 cis NA
Mean cell haemoglobin -0.0621 0.0302 0.0396 Wald ratio 1 cis NA
Birth length 0.0615 0.0302 0.0415 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.0498 0.0263 0.0578 Wald ratio 1 cis NA
HOMA-B -0.0186 0.00986 0.0598 Wald ratio 1 cis NA
Mean cell volume -0.141 0.0766 0.0651 Wald ratio 1 cis NA
…and 129 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

414 association rows across 172 traits (403 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
Eosinophil count 4e-476 rs13089722 22 GCST90002302 no MR -> candidate analysis
Eosinophil percentage of white cells 2e-467 rs6782812 7 GCST90002382 no MR -> candidate analysis
Monocyte count 8e-369 rs6789546 22 GCST90002344 no MR -> candidate analysis
Basophil count 9e-332 rs13089722 8 GCST90002296 no MR -> candidate analysis
monocyte (fraction, mean, inv-norm transformed) 1e-323 rs6798431 2 GCST90479705 no MR -> candidate analysis
Basophil (fraction, maximum, inv-norm transformed) 1e-323 rs4857909 3 GCST90479515 no MR -> candidate analysis
Basophil (fraction, minimum, inv-norm transformed) 1e-323 rs4857909 3 GCST90479517 no MR -> candidate analysis
eosinophil (fraction, maximum, inv-norm transformed) 1e-323 rs4857909 3 GCST90479604 no MR -> candidate analysis
eosinophil (absolute count, mean, inv-norm transformed) 1e-323 rs4857909 4 GCST90475291 no MR -> candidate analysis
eosinophil (fraction, mean, inv-norm transformed) 1e-323 rs4857909 3 GCST90479605 no MR -> candidate analysis
monocyte (fraction, maximum, inv-norm transformed) 4e-293 rs9289330 2 GCST90479704 no MR -> candidate analysis
monocyte (fraction, minimum, inv-norm transformed) 2e-284 rs9289330 3 GCST90475514 no MR -> candidate analysis
…and 160 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 221 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
COVID-19 0.474 common-variant locus no MR -> candidate analysis
aging 0.574 common-variant locus no MR -> candidate analysis
severe acute respiratory syndrome 0.474 common-variant locus no MR -> candidate analysis
myeloproliferative disorder 0.456 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.364 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.098 common-variant locus no MR -> candidate analysis

Of the 6 rows above, 6 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 (Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit 1)
gnomAD constraint pLI=1, LOEUF=0.35 — LoF-INTOLERANT
GWAS Catalog 144 unique SNPs / 362 rows
ClinVar 117 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance