CausalSentinel

Protein Dossier — CDSN (Corneodesmosin)

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)	-0.0215	0.00657	0.00107	Inverse variance weighted	2	trans	NA
Body mass index (BMI)	-0.0215	0.00657	0.00107	Inverse variance weighted	2	trans	NA
Weight	-0.0177	0.00581	0.00235	Inverse variance weighted	2	trans	NA
Weight	-0.0177	0.00581	0.00235	Inverse variance weighted	2	trans	NA
Major depressive disorder	-0.179	0.0612	0.0035	Inverse variance weighted	2	trans	NA
Major depressive disorder	-0.179	0.0612	0.0035	Inverse variance weighted	2	trans	NA
Childhood intelligence	-0.151	0.0558	0.00665	Wald ratio	1	trans	NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages	0.177	0.0771	0.0215	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages	0.177	0.0771	0.0215	Inverse variance weighted	2	trans	NA
Urinary albumin-to-creatinine ratio	-0.0397	0.0184	0.0312	Inverse variance weighted	2	trans	NA
Urinary albumin-to-creatinine ratio	-0.0397	0.0184	0.0312	Inverse variance weighted	2	trans	NA
Years of schooling	-0.0423	0.0199	0.0339	Inverse variance weighted	2	trans	NA
…and 186 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

27 association rows across 25 traits (23 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
Primary sclerosing cholangitis (MTAG)	1e-61	rs3094210	1	GCST90271580	no MR -> candidate analysis
Hemoglobin levels	5e-44	rs34182778	1	GCST010083	no MR -> candidate analysis
KIR2DL2 protein levels	7e-33	rs115510688	1	GCST90469684	no MR -> candidate analysis
PLB1 protein levels	1e-27	rs9501053	1	GCST90470253	no MR -> candidate analysis
Polyunsaturated fatty acid levels	1e-24	rs3130988	1	GCST90502134	no MR -> candidate analysis
FCRL1/TNFRSF13C protein level ratio	1e-21	rs1265045	1	GCST90314796	no MR -> candidate analysis
Omega-6 fatty acid levels	2e-21	rs3130988	1	GCST90502095	no MR -> candidate analysis
Mouth ulcers	3e-20	rs78479381	1	GCST007839	no MR -> candidate analysis
FEV1 x serum 25-hydroxyvitamin D interaction in never smoker	1e-19	rs3130985	1	GCST90590340	no MR -> candidate analysis
Psoriasis	6e-16	rs3130982 x rs9366778	1	GCST007023	MR: beta=-0.0548, p=0.404 (trans)
MHC class I polypeptide-related sequence B levels	4e-15	rs3130991	1	GCST90101317	no MR -> candidate analysis
Height	1e-14	rs1042127	1	GCST90245848	no MR -> candidate analysis
…and 13 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 1125 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
peeling skin syndrome 1	0.778	—	established (curated)	no MR -> candidate analysis
hypotrichosis 2	0.707	—	established (curated)	no MR -> candidate analysis
hypotrichosis simplex of the scalp	0.608	—	established (curated)	no MR -> candidate analysis
hereditary disease	0.316	—	established (curated)	no MR -> candidate analysis

Of the 4 rows above, 4 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=0.2, LOEUF=0.712 — LoF-tolerant
GWAS Catalog	843 unique SNPs / 2456 rows
ClinVar	179 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx	1 clinical annotations across 2 drugs

Caveats declared by the tools

• phenome — Top 30 of 1125 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 ‘CDSN’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 179 ClinVar records for this gene; it is a sample, not a rate.
• gwas_traits — Top 20 of 25 traits by best p-value, aggregated from 27 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/Q15517 — 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/ENSG00000204539/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/CDSN — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/CDSN — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CDSN%5Bgene%5D — ClinVar build Build260809-1055.1
• pharmgkb: https://www.pharmgkb.org/search?query=CDSN — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/data
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/CDSN — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T01:46:42 · 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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