CausalSentinel

Protein Dossier — DEFB112 (Beta-defensin 112)

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
Femoral neck bone mineral density -0.104 0.0469 0.0267 Wald ratio 1 trans NA
Eczema -0.327 0.17 0.0539 Wald ratio 1 trans NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0724 0.0477 0.129 Wald ratio 1 trans NA
Forearm bone mineral density -0.114 0.0949 0.231 Wald ratio 1 trans NA
Ovarian cancer -0.0779 0.0711 0.273 Wald ratio 1 trans NA
Endometrioid ovarian cancer -0.166 0.153 0.275 Wald ratio 1 trans NA
Clear cell ovarian cancer -0.222 0.208 0.287 Wald ratio 1 trans NA
Birth weight 0.0194 0.0188 0.303 Wald ratio 1 trans NA
High grade serous ovarian cancer -0.0817 0.0844 0.333 Wald ratio 1 trans NA
Invasive mucinous ovarian cancer 0.149 0.209 0.476 Wald ratio 1 trans NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0275 0.0401 0.493 Wald ratio 1 trans NA

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

86 association rows across 37 traits (68 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
CRISP3 protein levels 5e-168 rs141218036 8 GCST90468866 no MR -> candidate analysis
CRISP2 protein levels 1e-115 rs142915124 9 GCST90468865 no MR -> candidate analysis
Circulating CRISP2 levels 1e-63 rs142599928 1 GCST90860530 no MR -> candidate analysis
Bone mineral density mean 1e-61 rs139868657 2 GCST90321120 no MR -> candidate analysis
Metabolic syndrome 1e-18 rs4391262 3 GCST90444487 no MR -> candidate analysis
Body mass index 3e-18 rs72885809 23 GCST009871 no MR -> candidate analysis
Age at first sexual intercourse 1e-17 rs141547796 1 GCST90000047 no MR -> candidate analysis
Body mass index (MTAG) 5e-17 rs280322 5 GCST90179150 no MR -> candidate analysis
Whole body fat mass (UKB data field 23100) 1e-16 rs12528998 1 GCST90428121 no MR -> candidate analysis
Attention deficit hyperactivity disorder or autism spectrum 6e-13 rs141547796 1 GCST90134330 no MR -> candidate analysis
BMI (standard GWA) 6e-12 rs72885809 2 GCST90267268 no MR -> candidate analysis
Complication of amputation stump (PheCode 874) 2e-11 rs775233568 1 GCST90480619 no MR -> candidate analysis
…and 25 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 19 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 0.541 common-variant locus no MR -> candidate analysis
neoplasm 0.382 common-variant locus no MR -> candidate analysis
pneumonitis 0.382 common-variant locus no MR -> candidate analysis
placental abruption 0.377 common-variant locus no MR -> candidate analysis
cardiovascular disorder 0.355 common-variant locus no MR -> candidate analysis
metabolic syndrome 0.354 common-variant locus no MR -> candidate analysis
squamous cell carcinoma 0.353 common-variant locus no MR -> candidate analysis
trauma complication 0.353 common-variant locus no MR -> candidate analysis
glomerulonephritis 0.346 common-variant locus no MR -> candidate analysis
Abnormal male internal genitalia morphology 0.346 common-variant locus no MR -> candidate analysis
benign chondrogenic neoplasm 0.346 common-variant locus no MR -> candidate analysis
smoking initiation 0.343 common-variant locus no MR -> candidate analysis
muscular atrophy 0.316 common-variant locus no MR -> candidate analysis
corneal neovascularization 0.316 common-variant locus no MR -> candidate analysis
placenta praevia 0.044 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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=0.052, LOEUF=5.83 — LoF-tolerant
GWAS Catalog 83 unique SNPs / 96 rows
ClinVar 30 records; 10 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance