Protein Dossier — PI3 (Elafin)
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 |
| Systolic blood pressure automated reading |
0.0258 |
0.00824 |
0.00175 |
Wald ratio |
1 |
cis |
NA |
| Caudate volume |
48.8 |
16.1 |
0.00242 |
Wald ratio |
1 |
cis |
NA |
| 2hr glucose |
-0.184 |
0.0612 |
0.0027 |
Wald ratio |
1 |
cis |
NA |
| Lung cancer |
0.18 |
0.0639 |
0.00487 |
Wald ratio |
1 |
cis |
NA |
| Bipolar disorder |
-0.21 |
0.0791 |
0.00789 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: D25 Leiomyoma of uterus |
0.161 |
0.0608 |
0.00827 |
Wald ratio |
1 |
cis |
NA |
| Large vessel disease |
0.303 |
0.115 |
0.00834 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M23 Internal derangement of knee |
0.125 |
0.0479 |
0.00882 |
Wald ratio |
1 |
cis |
NA |
| LDL cholesterol |
-0.0413 |
0.0173 |
0.0171 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: gout |
0.138 |
0.059 |
0.0191 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: anxiety or panic attacks |
0.14 |
0.0606 |
0.0213 |
Wald ratio |
1 |
cis |
NA |
| Squamous cell lung cancer |
0.226 |
0.0997 |
0.0233 |
Wald ratio |
1 |
cis |
NA |
| …and 107 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4982_54_1 |
Elafin |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
19 association rows across 12 traits (17 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 |
| Circulating PI3 levels |
2e-584 |
rs56168207 |
4 |
GCST90859955 |
no MR -> candidate analysis |
| CD59/PI3 protein level ratio |
2e-451 |
rs56063128 |
1 |
GCST90313858 |
no MR -> candidate analysis |
| Elafin levels |
3e-127 |
rs35615384 |
3 |
GCST90247436 |
no MR -> candidate analysis |
| Serum levels of protein PI3 |
5e-45 |
rs6104052 |
1 |
GCST90088842 |
no MR -> candidate analysis |
| PI3 protein levels |
4e-40 |
rs77952882 |
1 |
GCST90470230 |
no MR -> candidate analysis |
| Elafin levels (PI3.4982.54.1) |
2e-35 |
rs16989763 |
1 |
GCST90241031 |
no MR -> candidate analysis |
| Blood protein levels |
5e-32 |
rs6104052 |
1 |
GCST006585 |
no MR -> candidate analysis |
| WFDC12 protein levels |
1e-23 |
rs549974756 |
3 |
GCST90471073 |
no MR -> candidate analysis |
| SDC4 protein levels |
4e-18 |
rs1983649 |
1 |
GCST90470559 |
no MR -> candidate analysis |
| Serum levels of protein SLPI |
1e-15 |
rs6130775 |
1 |
GCST90088681 |
no MR -> candidate analysis |
| Parental longevity (mother’s age at death) |
2e-6 |
rs34602589 |
1 |
GCST003393 |
no MR -> candidate analysis |
| IgG glycosylation |
3e-6 |
rs7361168 |
1 |
GCST001848 |
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 420 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 |
| placental abruption |
0.293 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormal male internal genitalia morphology |
0.165 |
— |
common-variant locus |
no MR -> candidate analysis |
| ectropion |
0.144 |
— |
common-variant locus |
no MR -> candidate analysis |
| entropion |
0.144 |
— |
common-variant locus |
no MR -> candidate analysis |
| bipolar disorder |
0.059 |
— |
common-variant locus |
MR: beta=-0.21, p=0.00789 (cis) |
Of the 5 rows above, 4 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 (Phosphoinositide 3-kinase regulatory subunit 4) |
| gnomAD constraint |
pLI=0.06, LOEUF=1.54 — LoF-tolerant |
| GWAS Catalog |
54 unique SNPs / 108 rows |
| ClinVar |
28 records; 10 pathogenic in sample of 28 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 420 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 ‘PI3’ and resolved to ‘Phosphoinositide 3-kinase regulatory subunit 4’ — confirm this is the intended target.clinvar — Pathogenic count is over the 28 record(s) retrieved, NOT over all 28 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 12 of 12 traits by best p-value, aggregated from 19 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/P19957 — 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/ENSG00000124102/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2189144/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PI3 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PI3 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PI3%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/PI3 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:19:45 · 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