Protein Dossier — PPA1 (Inorganic pyrophosphatase)
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 |
| Age at menopause |
-0.199 |
0.0498 |
6.33e-05 |
Wald ratio |
1 |
cis |
NA |
| Age at menarche |
0.0548 |
0.0146 |
1.80e-04 |
Wald ratio |
1 |
cis |
NA |
| HDL cholesterol |
-0.0314 |
0.00872 |
3.18e-04 |
Wald ratio |
1 |
cis |
NA |
| Cough on most days |
0.101 |
0.0288 |
4.63e-04 |
Wald ratio |
1 |
cis |
NA |
| Fractured or broken bones in last 5 years |
-0.0578 |
0.0205 |
0.00489 |
Wald ratio |
1 |
cis |
NA |
| Internalizing problems |
0.157 |
0.0576 |
0.00622 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: N20 Calculus of kidney and ureter |
0.166 |
0.0629 |
0.0084 |
Wald ratio |
1 |
cis |
NA |
| Lumbar spine bone mineral density |
-0.0594 |
0.0227 |
0.00895 |
Wald ratio |
1 |
cis |
NA |
| Neo-conscientiousness |
0.484 |
0.19 |
0.0109 |
Wald ratio |
1 |
cis |
NA |
| 2hr glucose |
0.0947 |
0.0473 |
0.0455 |
Wald ratio |
1 |
cis |
NA |
| Thalamus volume |
-30.9 |
15.9 |
0.0528 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
0.0101 |
0.00537 |
0.0599 |
Wald ratio |
1 |
cis |
NA |
| …and 107 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5021_13_1 |
PPase |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
6 association rows across 4 traits (5 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 |
| Inorganic pyrophosphatase levels |
2e-103 |
rs10823500 |
3 |
GCST90248117 |
no MR -> candidate analysis |
| LYVE1 protein levels |
1e-17 |
rs7077538 |
1 |
GCST90469832 |
no MR -> candidate analysis |
| ITGAM protein levels |
1e-13 |
rs76809526 |
1 |
GCST90469638 |
no MR -> candidate analysis |
| Red blood cell count |
5e-8 |
rs12771902 |
1 |
GCST007069 |
MR: beta=-0.00772, p=0.196 (cis) |
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 184 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 |
| frozen shoulder |
0.093 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 1 rows above, 1 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 (Inorganic pyrophosphatase) |
| gnomAD constraint |
pLI=0.00033, LOEUF=0.78 — LoF-tolerant |
| GWAS Catalog |
43 unique SNPs / 86 rows |
| ClinVar |
74 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 184 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 ‘PPA1’ and resolved to ‘Inorganic pyrophosphatase’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 74 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 4 of 4 traits by best p-value, aggregated from 6 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/Q15181 — 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/ENSG00000180817/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL6067227/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PPA1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PPA1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PPA1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/PPA1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:33:19 · 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