CausalSentinel

Protein Dossier — PCDH9 (Protocadherin-9)

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	0.0447	0.0133	7.73e-04	Wald ratio	1	cis	NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation	0.234	0.0721	0.0012	Wald ratio	1	cis	NA
Neuroticism	-0.0489	0.0188	0.00932	Wald ratio	1	cis	NA
Glioma	-0.7	0.278	0.0117	Wald ratio	1	cis	NA
Fractured bone site(s): Other bones	-0.165	0.067	0.0141	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: hypopituitarism	0.803	0.369	0.0293	Wald ratio	1	cis	NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities	0.161	0.0778	0.0386	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: osteoporosis	-0.266	0.139	0.0563	Wald ratio	1	cis	NA
Fasting proinsulin	-0.0714	0.0376	0.0574	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: osteoarthritis	-0.0906	0.0477	0.0578	Wald ratio	1	cis	NA
Fractured or broken bones in last 5 years	-0.0835	0.0442	0.0587	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: bone disorder	0.373	0.2	0.0624	Wald ratio	1	cis	NA
…and 71 more outcomes (see JSON)

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

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

231 association rows across 86 traits (124 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
PCDH9 protein levels	3e-223	rs5804316	10	GCST90470172	no MR -> candidate analysis
Smoking initiation	2e-42	rs9529052	8	GCST90243985	no MR -> candidate analysis
Adolescent idiopathic scoliosis	3e-35	rs9529199	2	GCST006287	no MR -> candidate analysis
Protocadherin-9 levels	3e-30	rs4883797	4	GCST90248876	no MR -> candidate analysis
Depression	1e-28	rs9592461	5	GCST007342	MR: beta=-0.476, p=0.399 (cis)
Educational attainment	1e-24	rs9540731	6	GCST90105038	no MR -> candidate analysis
Serum levels of protein PCDH9	2e-24	rs73196184	2	GCST90086340	no MR -> candidate analysis
Major depressive disorder	5e-24	rs7988498	4	GCST90020227	MR: beta=0.136, p=0.254 (cis)
Postoperative survival time in hepatocellular carcinoma	5e-20	rs913493	2	GCST007650	no MR -> candidate analysis
Insomnia	3e-18	rs9317586	9	GCST90131901	no MR -> candidate analysis
Smoking initiation (ever regular vs never regular) (MTAG)	2e-16	rs9529055	2	GCST007468	no MR -> candidate analysis
Blood protein levels	2e-15	rs1927820	1	GCST006585	no MR -> candidate analysis
…and 74 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 484 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
smoking initiation	0.718	—	common-variant locus	no MR -> candidate analysis
insomnia	0.712	—	common-variant locus	no MR -> candidate analysis
major depressive disorder	0.561	—	common-variant locus	MR: beta=0.136, p=0.254 (cis)
esophageal disorder	0.581	—	common-variant locus	no MR -> candidate analysis
placental abruption	0.581	—	common-variant locus	no MR -> candidate analysis
Abnormality of refraction	0.527	—	common-variant locus	no MR -> candidate analysis
adolescent idiopathic scoliosis	0.526	—	common-variant locus	no MR -> candidate analysis
gastroesophageal reflux disease	0.51	—	common-variant locus	no MR -> candidate analysis
ileostomy	0.49	—	common-variant locus	no MR -> candidate analysis
obesity disorder	0.483	—	common-variant locus	no MR -> candidate analysis
aortic disorder	0.482	—	common-variant locus	no MR -> candidate analysis
pericarditis	0.482	—	common-variant locus	no MR -> candidate analysis
spinal cord injury	0.472	—	common-variant locus	no MR -> candidate analysis
self-injurious ideation	0.467	—	common-variant locus	no MR -> candidate analysis
eye injury	0.427	—	common-variant locus	no MR -> candidate analysis

Of the 15 rows above, 14 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=0.99, LOEUF=0.478 — LoF-INTOLERANT
GWAS Catalog	122 unique SNPs / 302 rows
ClinVar	243 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 484 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 ‘PCDH9’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 243 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 86 traits by best p-value, aggregated from 231 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/Q9HC56 — 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/ENSG00000184226/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/PCDH9 — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/PCDH9 — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PCDH9%5Bgene%5D — ClinVar build Build260809-1055.1
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/PCDH9 — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T04:12:00 · 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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