CausalSentinel

Protein Dossier — RPRD1A (Regulation of nuclear pre-mRNA domain-containing protein 1A)

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
Alcohol intake frequency -0.0509 0.0182 0.00527 Wald ratio 1 trans NA
Depressive symptoms -0.048 0.0192 0.0124 Wald ratio 1 trans NA
Glioma 0.556 0.224 0.013 Wald ratio 1 trans NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal 0.208 0.0853 0.0147 Wald ratio 1 trans NA
Cardioembolic stroke 0.384 0.162 0.0176 Wald ratio 1 trans NA
Non-cancer illness code self-reported: arthritis (nos) 0.256 0.112 0.0215 Wald ratio 1 trans NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.175 0.085 0.0393 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension -0.0452 0.022 0.0402 Wald ratio 1 trans NA
Heel bone mineral density (BMD) T-score automated -0.031 0.016 0.0521 Wald ratio 1 trans NA
Height -0.0283 0.0149 0.057 Wald ratio 1 trans NA
Non-cancer illness code self-reported: asthma -0.0678 0.037 0.067 Wald ratio 1 trans NA
Mean cell volume -0.238 0.13 0.0672 Wald ratio 1 trans NA
…and 91 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

9 association rows across 5 traits (7 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 hemoglobin 8e-14 rs28791905 5 GCST90002326 no MR -> candidate analysis
Mean corpuscular volume 1e-11 rs74277390 1 GCST90002392 no MR -> candidate analysis
Free Cholesterol to Cholesteryl Esters in Large HDL ratio 2e-9 rs145925439 1 GCST90827800 no MR -> candidate analysis
Tuberculosis 2e-6 rs75764086 1 GCST90275070 no MR -> candidate analysis
Tenofovir clearance in HIV infection 6e-6 rs17562912 1 GCST006073 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 36 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
Nasal polyposis 0.401 common-variant locus no MR -> candidate analysis
bipolar disorder 0.054 common-variant locus MR: beta=0.167, p=0.162 (trans)
Loss of consciousness 0.043 common-variant locus no MR -> candidate analysis
deficiency anemia 0.043 common-variant locus no MR -> candidate analysis
Phenotypic abnormality 0.038 common-variant locus no MR -> candidate analysis
hyperaldosteronism 0.035 common-variant locus no MR -> candidate analysis

Of the 6 rows above, 5 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=1, LOEUF=0.415 — LoF-INTOLERANT
GWAS Catalog 19 unique SNPs / 38 rows
ClinVar 86 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance