CausalSentinel

Protein Dossier — DEFB119 (Beta-defensin 119)

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 -0.676 0.125 6.44e-08 Wald ratio 1 trans 0.991
Lung cancer -0.423 0.0868 1.11e-06 Wald ratio 1 trans NA
Alcohol intake frequency -0.0332 0.012 0.00568 Inverse variance weighted 2 trans NA
Alcohol intake frequency -0.0332 0.012 0.00568 Inverse variance weighted 2 trans NA
High grade serous ovarian cancer 0.184 0.0728 0.0114 Wald ratio 1 trans NA
Thyroid cancer 1.19 0.482 0.0136 Wald ratio 1 trans NA
Eye problems or disorders: Diabetes related eye disease -0.00475 0.00198 0.0165 Inverse variance weighted 2 trans NA
Eye problems or disorders: Diabetes related eye disease -0.00475 0.00198 0.0165 Inverse variance weighted 2 trans NA
Age at menopause 0.275 0.118 0.0196 Wald ratio 1 trans NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages -0.00138 0.000599 0.0209 Inverse variance weighted 2 trans NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages -0.00138 0.000599 0.0209 Inverse variance weighted 2 trans NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter -0.0016 0.000696 0.0215 Inverse variance weighted 2 trans NA
…and 152 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

7 association rows across 7 traits (7 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
Circulating ENTPD6 levels (id: OID01322_OID20100) 2e-48 rs187219010 1 GCST90860517 no MR -> candidate analysis
Circulating ENTPD6 levels (id: OID01089_OID20100) 2e-48 rs187219010 1 GCST90860303 no MR -> candidate analysis
Liver enzyme levels (alkaline phosphatase) 8e-20 rs6119324 1 GCST90013406 no MR -> candidate analysis
CST7 protein levels 4e-18 rs147882083 1 GCST90468897 no MR -> candidate analysis
Serum alkaline phosphatase levels 3e-15 rs73108020 1 GCST90018942 no MR -> candidate analysis
Heel bone mineral density 9e-10 rs77241905 1 GCST007066 MR: beta=0.0133, p=0.206 (trans)
Mean corpuscular hemoglobin 4e-8 rs77241905 1 GCST007068 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 16 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
hypertensive disorder 0.085 common-variant locus no MR -> candidate analysis
response to xenobiotic stimulus 0.065 common-variant locus no MR -> candidate analysis
adolescent idiopathic scoliosis 0.057 common-variant locus no MR -> candidate analysis
crush injury 0.053 common-variant locus no MR -> candidate analysis
gastric carcinoma 0.051 common-variant locus no MR -> candidate analysis
alcohol drinking 0.044 common-variant locus no MR -> candidate analysis

Of the 6 rows above, 6 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=0.033, LOEUF=3.07 — LoF-tolerant
GWAS Catalog 29 unique SNPs / 58 rows
ClinVar 55 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance