Protein Dossier — PDIA3 (Protein disulfide-isomerase A3)
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 |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.176 |
0.0423 |
3.20e-05 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.168 |
0.0505 |
8.79e-04 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K43 Ventral hernia |
0.512 |
0.156 |
0.00105 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: diverticular disease or diverticulitis |
0.367 |
0.112 |
0.00106 |
Wald ratio |
1 |
cis |
NA |
| PGC cross-disorder traits |
0.245 |
0.0814 |
0.00258 |
Wald ratio |
1 |
cis |
NA |
| Alcohol intake frequency |
0.0739 |
0.0249 |
0.00302 |
Wald ratio |
1 |
cis |
NA |
| Schizophrenia |
0.205 |
0.0716 |
0.00429 |
Wald ratio |
1 |
cis |
NA |
| ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.209 |
0.0778 |
0.00732 |
Wald ratio |
1 |
cis |
NA |
| Thyroid cancer |
-1.48 |
0.553 |
0.00733 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K20 Oesophagitis |
0.318 |
0.126 |
0.0119 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: anxiety or panic attacks |
0.278 |
0.112 |
0.013 |
Wald ratio |
1 |
cis |
NA |
| Happiness |
0.05 |
0.0209 |
0.0166 |
Wald ratio |
1 |
cis |
NA |
| …and 103 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4719_58_2 |
Protein disulfide isomerase A3 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
11 association rows across 11 traits (10 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 |
| Self-reported math ability (MTAG) |
1e-9 |
rs3087657 |
1 |
GCST006569 |
no MR -> candidate analysis |
| Free cholesterol in IDL |
1e-9 |
rs117519814 |
1 |
GCST90827783 |
no MR -> candidate analysis |
| Free cholesterol levels in IDL |
3e-9 |
rs117519814 |
1 |
GCST90092835 |
no MR -> candidate analysis |
| Free cholesterol levels in large LDL |
4e-9 |
rs117519814 |
1 |
GCST90092860 |
no MR -> candidate analysis |
| Cholesterol in IDL |
5e-9 |
rs117519814 |
1 |
GCST90827778 |
no MR -> candidate analysis |
| Cholesterol levels in IDL |
1e-8 |
rs117519814 |
1 |
GCST90092831 |
no MR -> candidate analysis |
| Free cholesterol in large LDL |
1e-8 |
rs117519814 |
1 |
GCST90827814 |
no MR -> candidate analysis |
| Cholesteryl ester levels in IDL |
2e-8 |
rs117519814 |
1 |
GCST90092833 |
no MR -> candidate analysis |
| Free cholesterol levels in LDL |
2e-8 |
rs117519814 |
1 |
GCST90092885 |
no MR -> candidate analysis |
| Cholesteryl Esters in IDL |
2e-8 |
rs117519814 |
1 |
GCST90827780 |
no MR -> candidate analysis |
| Aerodigestive squamous cell cancer (pleiotropy) |
4e-6 |
rs8040336 |
1 |
GCST012213 |
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 384 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 |
| Intellectual disability |
0.426 |
— |
established (curated) |
no MR -> candidate analysis |
| cancer |
0.299 |
— |
common-variant locus |
MR: beta=0.176, p=3.20e-05 (cis) |
| autoimmune thyroid disease |
0.3 |
— |
common-variant locus |
no MR -> candidate analysis |
| celiac disease |
0.3 |
— |
common-variant locus |
no MR -> candidate analysis |
| mathematical ability |
0.287 |
— |
common-variant locus |
no MR -> candidate analysis |
| type 2 diabetes mellitus |
0.233 |
— |
common-variant locus |
no MR -> candidate analysis |
| diabetes mellitus |
0.214 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 7 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 (Protein disulfide-isomerase A3) |
| gnomAD constraint |
pLI=1, LOEUF=0.427 — LoF-INTOLERANT |
| GWAS Catalog |
30 unique SNPs / 60 rows |
| ClinVar |
125 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 384 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘PDIA3’ and resolved to ‘Protein disulfide-isomerase A3’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 125 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 11 of 11 traits by best p-value, aggregated from 11 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/P30101 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000167004/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4296001/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PDIA3 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PDIA3 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PDIA3%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/PDIA3 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:15:59 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none