CausalSentinel

Protein Dossier — PDIA5 (Protein disulfide-isomerase A5)

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
Platelet count 3.36 0.927 2.87e-04 Wald ratio 1 cis NA
Mean platelet volume -0.00767 0.0023 8.58e-04 Wald ratio 1 cis NA
Hip osteoarthritis 0.139 0.0576 0.0157 Wald ratio 1 cis NA
Alcohol intake frequency 0.0166 0.00695 0.0171 Wald ratio 1 cis NA
Sodium in urine 0.0106 0.00462 0.0219 Wald ratio 1 cis NA
Hirschsprung’s disease -0.551 0.248 0.0264 Wald ratio 1 cis NA
Internalizing problems -0.092 0.0422 0.0291 Wald ratio 1 cis NA
Non-cancer illness code self-reported: muscle or soft tissue injuries -0.132 0.0636 0.0376 Wald ratio 1 cis NA
Chronic kidney disease 0.0613 0.0307 0.0455 Wald ratio 1 cis NA
Diagnoses - main ICD10: D25 Leiomyoma of uterus -0.0906 0.0455 0.0465 Wald ratio 1 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.056 0.0286 0.0499 Wald ratio 1 cis NA
Systemic lupus erythematosus 0.169 0.0902 0.0606 Wald ratio 1 cis NA
…and 94 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

132 association rows across 112 traits (122 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
Protein disulfide-isomerase A5 levels 7e-1452 rs3804749 1 GCST90248919 no MR -> candidate analysis
Blood protein levels 6e-729 rs920900 3 GCST006585 no MR -> candidate analysis
PDIA5 protein levels 3e-270 rs3804749 1 GCST90470196 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 5e-129 rs13314114 1 GCST90468087 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 3e-128 rs920900 2 GCST90838669 no MR -> candidate analysis
Protein disulfide-isomerase A5 levels (PDIA5.5593.11.3) 4e-110 rs2278668 1 GCST90242438 no MR -> candidate analysis
Platelet count 2e-93 rs3804749 10 GCST90002361 MR: beta=3.36, p=2.87e-04 (cis)
Platelet distribution width (UKB data field 30110) 5e-92 rs3792366 1 GCST90468097 no MR -> candidate analysis
Platelet distribution width 4e-79 rs3804749 2 GCST90002401 no MR -> candidate analysis
Mean platelet volume 2e-72 rs13314114 2 GCST90002395 MR: beta=-0.00767, p=8.58e-04 (cis)
platelet count (maximum, inv-norm transformed) 2e-69 rs3804749 2 GCST90476296 no MR -> candidate analysis
Platelet count (UKB data field 30080) 1e-68 rs3804749 1 GCST90468095 no MR -> candidate analysis
…and 100 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 127 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
blood coagulation disease 0.482 common-variant locus no MR -> candidate analysis
spinal stenosis 0.476 common-variant locus no MR -> candidate analysis
temporomandibular joint disorder 0.455 common-variant locus no MR -> candidate analysis
placenta praevia 0.429 common-variant locus no MR -> candidate analysis
cancer 0.053 common-variant locus MR: beta=-0.132, p=0.0376 (cis)
Pain 0.121 common-variant locus MR: beta=0.0194, p=0.385 (cis)
Alzheimer disease 0.117 common-variant locus no MR -> candidate analysis
inborn disorder of amino acid metabolism 0.103 common-variant locus no MR -> candidate analysis
celiac disease 0.06 common-variant locus no MR -> candidate analysis
alcohol drinking 0.059 common-variant locus no MR -> candidate analysis
seasonal allergic rhinitis 0.059 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.053 common-variant locus no MR -> candidate analysis
stroke disorder 0.053 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.053 common-variant locus MR: beta=0.0346, p=0.421 (cis)
coronary artery disorder 0.053 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 12 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 (Protein disulfide-isomerase A5)
gnomAD constraint pLI=4.2e-15, LOEUF=0.93 — LoF-tolerant
GWAS Catalog 56 unique SNPs / 104 rows
ClinVar 137 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance