CausalSentinel

Protein Dossier — VWC2 (Brorin)

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
Chronic kidney disease 0.194 0.0647 0.0027 Wald ratio 1 cis NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) 0.159 0.0607 0.00877 Wald ratio 1 cis NA
Forearm bone mineral density 0.155 0.0654 0.0175 Wald ratio 1 cis NA
Diagnoses - main ICD10: J33 Nasal polyp 0.257 0.114 0.0243 Wald ratio 1 cis NA
Primary sclerosing cholangitis -0.307 0.141 0.0297 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.144 0.0661 0.0297 Wald ratio 1 cis NA
Urate 0.05 0.0232 0.0314 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse 0.221 0.11 0.0452 Wald ratio 1 cis NA
Invasive mucinous ovarian cancer 0.374 0.187 0.0455 Wald ratio 1 cis NA
Clear cell ovarian cancer 0.36 0.189 0.0564 Wald ratio 1 cis NA
Ovarian cancer 0.114 0.0606 0.059 Wald ratio 1 cis NA
Pallidum volume -15.1 8.02 0.0602 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

120 association rows across 57 traits (91 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
EPHB6/VWC2 protein level ratio 2e-1410 rs482968 1 GCST90314683 no MR -> candidate analysis
EFNA4/VWC2 protein level ratio 3e-1371 rs482968 1 GCST90314607 no MR -> candidate analysis
Circulating VWC2 levels 2e-1294 rs482968 6 GCST90859657 no MR -> candidate analysis
LAYN/VWC2 protein level ratio 5e-1221 rs482968 1 GCST90315293 no MR -> candidate analysis
VWC2 protein levels 1e-228 rs201115864 20 GCST90471064 no MR -> candidate analysis
Brorin levels 2e-94 rs1974955 5 GCST90246743 no MR -> candidate analysis
Brorin levels (VWC2.11121.56.3) 7e-55 rs372065719 4 GCST90240475 no MR -> candidate analysis
Serum levels of protein VWC2 6e-36 rs79259707 2 GCST90086551 no MR -> candidate analysis
Blood protein levels 1e-22 rs79259707 1 GCST006585 no MR -> candidate analysis
Educational attainment 5e-22 rs55633081 2 GCST90105038 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 1e-19 rs10279413 3 GCST90838669 no MR -> candidate analysis
Monocyte percentage (UKB data field 30190) 4e-19 rs10269283 2 GCST90468091 no MR -> candidate analysis
…and 45 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 54 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
obesity disorder 0.658 common-variant locus no MR -> candidate analysis
smoking initiation 0.566 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.505 common-variant locus no MR -> candidate analysis
ankylosing spondylitis 0.482 common-variant locus MR: beta=-0.249, p=0.345 (cis)
Alzheimer disease 0.478 common-variant locus no MR -> candidate analysis
Pancreatic pseudocyst 0.393 common-variant locus no MR -> candidate analysis
stroke disorder 0.346 common-variant locus no MR -> candidate analysis
frozen shoulder 0.346 common-variant locus no MR -> candidate analysis
psoriatic arthritis 0.346 common-variant locus no MR -> candidate analysis
keratoconus 0.346 common-variant locus no MR -> candidate analysis
systemic lupus erythematosus 0.346 common-variant locus no MR -> candidate analysis
alcohol drinking 0.346 common-variant locus no MR -> candidate analysis
benign neoplasm of adrenal gland 0.346 common-variant locus no MR -> candidate analysis
skin disorder 0.346 common-variant locus no MR -> candidate analysis
nutritional deficiency disease 0.346 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=0.048, LOEUF=0.735 — LoF-tolerant
GWAS Catalog 90 unique SNPs / 167 rows
ClinVar 79 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance