CausalSentinel

Protein Dossier — PPY (Pancreatic polypeptide prohormone)

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
Cancer code self-reported: small intestine or small bowel cancer	0.815	0.278	0.00338	Wald ratio	1	trans	NA
Non-cancer illness code self-reported: hypertension	-0.0589	0.022	0.00733	Wald ratio	1	trans	NA
Birth weight	0.05	0.0211	0.018	Wald ratio	1	trans	NA
Non-cancer illness code self-reported: vitiligo	0.841	0.37	0.0231	Wald ratio	1	trans	NA
Diagnoses - main ICD10: K20 Oesophagitis	0.221	0.0995	0.0263	Wald ratio	1	trans	NA
Diagnoses - main ICD10: N81 Female genital prolapse	-0.313	0.142	0.0275	Wald ratio	1	trans	NA
Eye problems or disorders: Injury or trauma resulting in loss of vision	0.264	0.124	0.0326	Wald ratio	1	trans	NA
Systolic blood pressure automated reading	-0.0262	0.0124	0.0353	Wald ratio	1	trans	NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis)	-0.138	0.066	0.0364	Wald ratio	1	trans	NA
Diastolic blood pressure automated reading	-0.0258	0.0125	0.0385	Wald ratio	1	trans	NA
Cancer code self-reported: prostate cancer	0.233	0.114	0.0411	Wald ratio	1	trans	NA
Vascular or heart problems diagnosed by doctor: Angina	0.122	0.0605	0.0446	Wald ratio	1	trans	NA
…and 51 more outcomes (see JSON)

2. pQTL instrument availability (Tier-B probe)

Dataset	Trait	Author	Year
prot-c-4588_1_2	PH	Suhre K	2019

3. GWAS Catalog results — traits with signal at this locus

No GWAS Catalog associations mapped to this gene.

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 307 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
pathological myopia	0.122	—	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	not available — no ChEMBL target (undrugged)
gnomAD constraint	pLI=0.029, LOEUF=1.27 — LoF-tolerant
GWAS Catalog	57 unique SNPs / 114 rows
ClinVar	24 records; 9 pathogenic in sample of 24
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 307 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.
• chembl — No ChEMBL target for ‘PPY’.
• clinvar — Pathogenic count is over the 24 record(s) retrieved, NOT over all 24 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 — No GWAS Catalog associations mapped to this gene.

Sources

• uniprot: https://www.uniprot.org/uniprotkb/P01298 — 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 v3.0
• phenome: https://platform.opentargets.org/target/ENSG00000108849/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/PPY — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/PPY — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PPY%5Bgene%5D — ClinVar build Build260809-1055.1

Provenance

• Generated: 2026-08-14T04:35:24 · 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

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