Protein Dossier — PDE5A (cGMP-specific 3’,5’-cyclic phosphodiesterase)
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 |
| Non-cancer illness code self-reported: uterine fibroids |
0.181 |
0.0523 |
5.29e-04 |
Wald ratio |
1 |
cis |
NA |
| Height |
-0.0312 |
0.00924 |
7.27e-04 |
Wald ratio |
1 |
cis |
NA |
| Vascular or heart problems diagnosed by doctor: Angina |
-0.126 |
0.0493 |
0.0108 |
Wald ratio |
1 |
cis |
NA |
| Lumbar spine bone mineral density |
0.0718 |
0.0282 |
0.0108 |
Wald ratio |
1 |
cis |
NA |
| Alcohol intake frequency |
0.0282 |
0.0114 |
0.0136 |
Wald ratio |
1 |
cis |
NA |
| Coronary heart disease |
-0.0709 |
0.0293 |
0.0156 |
Wald ratio |
1 |
cis |
NA |
| Chronic kidney disease |
0.115 |
0.0478 |
0.0164 |
Wald ratio |
1 |
cis |
NA |
| Myocardial infarction |
-0.0699 |
0.0324 |
0.0313 |
Wald ratio |
1 |
cis |
NA |
| Body fat |
-0.0369 |
0.0172 |
0.0317 |
Wald ratio |
1 |
cis |
NA |
| Birth weight |
0.0245 |
0.0115 |
0.0324 |
Wald ratio |
1 |
cis |
NA |
| High grade serous ovarian cancer |
0.109 |
0.0512 |
0.0341 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: N81 Female genital prolapse |
-0.16 |
0.0764 |
0.0364 |
Wald ratio |
1 |
cis |
NA |
| …and 101 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5256_86_3 |
PDE5A |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
102 association rows across 55 traits (92 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 |
| cGMP-specific 3,5-cyclic phosphodiesterase levels |
1e-162 |
rs59867181 |
4 |
GCST90248907 |
no MR -> candidate analysis |
| PDE5A protein levels |
2e-108 |
rs58583086 |
3 |
GCST90470187 |
no MR -> candidate analysis |
| Height |
7e-90 |
rs17051339 |
16 |
GCST90245848 |
MR: beta=-0.0312, p=7.27e-04 (cis) |
| FABP2 protein levels |
6e-37 |
rs4452411 |
1 |
GCST90469174 |
no MR -> candidate analysis |
| Hematological traits (multi-trait analysis) |
2e-31 |
rs13122709 |
2 |
GCST90838669 |
no MR -> candidate analysis |
| Platelet count |
1e-28 |
rs7672519 |
4 |
GCST90662907 |
MR: beta=-2.11, p=0.0953 (cis) |
| Diastolic blood pressure |
3e-21 |
rs66887589 |
7 |
GCST90310295 |
MR: beta=-0.01, p=0.205 (cis) |
| Refractive error |
1e-19 |
rs7666824 |
2 |
GCST90841193 |
no MR -> candidate analysis |
| Diastolic blood pressure (MTAG) |
9e-19 |
rs66887589 |
1 |
GCST90449057 |
no MR -> candidate analysis |
| Impedance of arm left (UKB data field 23110) |
1e-16 |
rs749526 |
1 |
GCST90468171 |
no MR -> candidate analysis |
| cGMP-specific 3’,5’-cyclic phosphodiesterase levels |
3e-15 |
rs151102303 |
1 |
GCST90162352 |
no MR -> candidate analysis |
| Waist circumference adjusted for body mass index |
2e-14 |
rs62321172 |
4 |
GCST90020029 |
no MR -> candidate analysis |
| …and 43 more traits (see JSON) |
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|
|
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|
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 723 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 |
| coronary artery disorder |
0.715 |
— |
common-variant locus |
no MR -> candidate analysis |
| cardiovascular disorder |
0.389 |
— |
common-variant locus |
no MR -> candidate analysis |
| obesity disorder |
0.498 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 3 rows above, 3 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 (PDE5A/PDE6C) |
| gnomAD constraint |
pLI=7.9e-13, LOEUF=0.745 — LoF-tolerant |
| GWAS Catalog |
94 unique SNPs / 170 rows |
| ClinVar |
167 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 723 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 ‘PDE5A’ and resolved to ‘PDE5A/PDE6C’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 167 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 20 of 55 traits by best p-value, aggregated from 102 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/O76074 — 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/ENSG00000138735/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4523626/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PDE5A — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PDE5A — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PDE5A%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/PDE5A — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:14:48 · 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