CausalSentinel

Protein Dossier — DEFB1 (Beta-defensin 1)

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
Squamous cell lung cancer	0.447	0.138	0.00123	Wald ratio	1	trans	NA
Happiness	-0.0175	0.00718	0.0146	Inverse variance weighted	2	cis	NA
Happiness	-0.0175	0.00718	0.0146	Inverse variance weighted	2	trans	NA
Eye problems or disorders: Injury or trauma resulting in loss of vision	-0.211	0.0944	0.0252	Inverse variance weighted	2	cis	NA
Eye problems or disorders: Injury or trauma resulting in loss of vision	-0.211	0.0944	0.0252	Inverse variance weighted	2	trans	NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema	0.0484	0.0245	0.0487	Inverse variance weighted	2	cis	NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema	0.0484	0.0245	0.0487	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: L03 Cellulitis	0.114	0.0578	0.0489	Inverse variance weighted	2	cis	NA
Diagnoses - main ICD10: L03 Cellulitis	0.114	0.0578	0.0489	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: J33 Nasal polyp	-0.196	0.104	0.0592	Inverse variance weighted	2	cis	NA
Diagnoses - main ICD10: J33 Nasal polyp	-0.196	0.104	0.0592	Inverse variance weighted	2	trans	NA
Femoral neck bone mineral density	0.0344	0.0198	0.0829	Wald ratio	1	cis	NA
…and 101 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

11 association rows across 9 traits (9 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
Serum levels of protein DEFB1	2e-103	rs2741130	2	GCST90089538	no MR -> candidate analysis
Cerebrospinal fluid protein DEFB1 levels	4e-80	rs2977772	1	GCST90944743	no MR -> candidate analysis
Beta-defensin 1 levels (DEFB1.6629.3.3)	3e-39	rs2702945	1	GCST90240410	no MR -> candidate analysis
Circulating CDSN levels	3e-26	rs2293959	1	GCST90860191	no MR -> candidate analysis
Blood cell traits latent factor 22 (white cell)	2e-20	rs5743467	2	GCST90559264	no MR -> candidate analysis
WFDC12 protein levels	7e-13	rs2702945	1	GCST90471073	no MR -> candidate analysis
Tanner 2 to Tanner 4 pubertal stage transition (joint longit	4e-8	rs2741127	1	GCST90444215	no MR -> candidate analysis
Plasma kynurenine to tryptophan ratio in major depressive di	2e-7	rs5743467	1	GCST005343	no MR -> candidate analysis
Plasma kynurenine levels in major depressive disorder	8e-7	rs5743467	1	GCST005342	no MR -> candidate analysis

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

Top diseases by Open Targets association (of 455 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
cervical carcinoma	0.39	—	common-variant locus	no MR -> candidate analysis
diabetes mellitus	0.367	—	common-variant locus	no MR -> candidate analysis
cardioembolic stroke	0.355	—	common-variant locus	no MR -> candidate analysis
response to xenobiotic stimulus	0.191	—	common-variant locus	no MR -> candidate analysis
gastrointestinal disease	0.162	—	common-variant locus	no MR -> candidate analysis

Of the 5 rows above, 5 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=0.0093, LOEUF=3.51 — LoF-tolerant
GWAS Catalog	147 unique SNPs / 353 rows
ClinVar	148 records; 8 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 455 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 ‘DEFB1’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 148 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 9 of 9 traits by best p-value, aggregated from 11 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/P60022 — 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/ENSG00000164825/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/DEFB1 — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/DEFB1 — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=DEFB1%5Bgene%5D — ClinVar build Build260809-1055.1
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/DEFB1 — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T02:15:23 · 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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