Protein Dossier — PON1 (Serum paraoxonase/arylesterase 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 |
| Body mass index (BMI) |
0.00803 |
0.00312 |
0.00996 |
Wald ratio |
1 |
cis |
NA |
| Lung cancer |
-0.0545 |
0.0222 |
0.0139 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages |
0.0898 |
0.0397 |
0.0235 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: joint disorder |
-0.113 |
0.0511 |
0.0275 |
Wald ratio |
1 |
cis |
NA |
| Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis |
0.797 |
0.364 |
0.0284 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K20 Oesophagitis |
0.0608 |
0.0296 |
0.0401 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: J33 Nasal polyp |
0.0844 |
0.0417 |
0.0428 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: bone disorder |
0.12 |
0.0592 |
0.0429 |
Wald ratio |
1 |
cis |
NA |
| Age at menopause |
-0.0471 |
0.0236 |
0.0455 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone |
0.0657 |
0.033 |
0.0465 |
Wald ratio |
1 |
cis |
NA |
| Weight |
0.00536 |
0.00275 |
0.0514 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Wrist |
-0.0454 |
0.0233 |
0.0514 |
Wald ratio |
1 |
cis |
NA |
| …and 104 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4261_55_2 |
paraoxonase 1 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
254 association rows across 190 traits (248 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 PON3 levels |
2e-891 |
rs10953142 |
1 |
GCST90859987 |
no MR -> candidate analysis |
| Testis-expressed sequence 29 protein levels |
4e-400 |
rs662 |
2 |
GCST90249809 |
no MR -> candidate analysis |
| Myeloid leukemia factor 1 levels |
3e-316 |
rs3917529 |
1 |
GCST90248481 |
no MR -> candidate analysis |
| Paraoxonase activity |
1e-303 |
rs2057681 |
2 |
GCST001677 |
no MR -> candidate analysis |
| PON1 protein levels |
2e-215 |
rs705379 |
13 |
GCST90453213 |
no MR -> candidate analysis |
| Proteasome subunit beta type-9 levels |
6e-148 |
rs1157745 |
2 |
GCST90249140 |
no MR -> candidate analysis |
| T-cell surface protein tactile levels |
1e-99 |
rs1157745 |
2 |
GCST90249758 |
no MR -> candidate analysis |
| Syntaxin-10 levels (STX10.12842.43.3) |
1e-93 |
rs662 |
1 |
GCST90242944 |
no MR -> candidate analysis |
| Testis-expressed sequence 29 protein levels (TEX29.10557.6.3 |
3e-93 |
rs3917539 |
2 |
GCST90242989 |
no MR -> candidate analysis |
| Filamin-A level in Chronic kidney disease with hypertension |
6e-81 |
rs662 |
1 |
GCST90233147 |
no MR -> candidate analysis |
| PON2 protein levels |
2e-79 |
rs3917510 |
3 |
GCST90470286 |
no MR -> candidate analysis |
| NHL repeat-containing protein 3 levels |
3e-79 |
rs1157745 |
1 |
GCST90248677 |
no MR -> candidate analysis |
| …and 178 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 795 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 |
| amyotrophic lateral sclerosis |
0.525 |
— |
established (curated) |
no MR -> candidate analysis |
| atopic eczema |
0.554 |
— |
common-variant locus |
no MR -> candidate analysis |
| obesity disorder |
0.475 |
— |
common-variant locus |
no MR -> candidate analysis |
| idiopathic pulmonary fibrosis |
0.388 |
— |
common-variant locus |
no MR -> candidate analysis |
| type 2 diabetes mellitus |
0.057 |
— |
common-variant locus |
no MR -> candidate analysis |
| diabetes mellitus |
0.057 |
— |
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 (Serum paraoxonase/arylesterase 1) |
| gnomAD constraint |
pLI=1.5e-12, LOEUF=1.24 — LoF-tolerant |
| GWAS Catalog |
120 unique SNPs / 251 rows |
| ClinVar |
97 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 795 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 ‘PON1’ and resolved to ‘Serum paraoxonase/arylesterase 1’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 97 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 190 traits by best p-value, aggregated from 254 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/P27169 — 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/ENSG00000005421/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3167/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PON1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PON1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PON1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/PON1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:32:03 · 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: pharmgkb