CausalSentinel

Protein Dossier — VSIG2 (V-set and immunoglobulin domain-containing protein 2)

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
Height -0.0438 0.0126 4.92e-04 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) -0.023 0.00864 0.00779 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis -0.593 0.223 0.0079 Wald ratio 1 trans NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis 0.201 0.0778 0.0098 Wald ratio 1 trans NA
Fractured bone site(s): Wrist 0.153 0.0615 0.013 Wald ratio 1 trans NA
Bipolar disorder 0.245 0.102 0.0167 Wald ratio 1 trans NA
Cigarettes smoked per day 0.827 0.349 0.0178 Wald ratio 1 trans NA
Myocardial infarction 0.1 0.0426 0.0187 Wald ratio 1 trans NA
Forced vital capacity (FVC) -0.0186 0.00819 0.0234 Wald ratio 1 trans NA
Body mass index (BMI) 0.0224 0.00999 0.0253 Wald ratio 1 trans NA
Diastolic blood pressure automated reading -0.021 0.0102 0.0405 Wald ratio 1 trans NA
Eye problems or disorders: Diabetes related eye disease 0.215 0.105 0.0413 Wald ratio 1 trans NA
…and 83 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

14 association rows across 10 traits (13 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
VSIG2 protein levels 3e-178 rs11604175 1 GCST90471051 no MR -> candidate analysis
Circulating ESAM levels 1e-96 rs11219769 1 GCST90860618 no MR -> candidate analysis
Serum levels of protein ESAM 2e-32 rs11604175 2 GCST90088164 no MR -> candidate analysis
Blood protein levels 5e-22 rs11604175 2 GCST006585 no MR -> candidate analysis
Endothelial cell-selective adhesion molecule levels (ESAM.78 4e-17 rs11219769 1 GCST90241050 no MR -> candidate analysis
Endothelial cell-selective adhesion molecule levels 4e-15 rs561529099 3 GCST90247390 no MR -> candidate analysis
V-set and immunoglobulin domain-containing protein 2 levels 5e-14 rs11604175 1 GCST90179466 no MR -> candidate analysis
Diastolic blood pressure 2e-9 rs11604175 1 GCST90310295 MR: beta=-0.021, p=0.0405 (trans)
Irritable bowel syndrome or schizophrenia (pleiotropy) 1e-8 rs11604175 1 GCST90271327 no MR -> candidate analysis
Systolic blood pressure 9e-6 rs11604175 1 GCST90310294 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 92 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
schizophrenia 0.69 common-variant locus no MR -> candidate analysis
irritable bowel syndrome 0.534 common-variant locus no MR -> candidate analysis
autism spectrum disorder 0.144 common-variant locus no MR -> candidate analysis
anorexia nervosa 0.134 common-variant locus no MR -> candidate analysis
preeclampsia 0.131 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.126 common-variant locus no MR -> candidate analysis
Tourette syndrome 0.115 common-variant locus no MR -> candidate analysis
bipolar disorder 0.115 common-variant locus MR: beta=0.245, p=0.0167 (trans)
intelligence 0.115 common-variant locus MR: beta=-0.0803, p=0.135 (trans)
obsessive-compulsive disorder 0.115 common-variant locus no MR -> candidate analysis
major depressive disorder 0.115 common-variant locus no MR -> candidate analysis
obesity disorder 0.077 common-variant locus no MR -> candidate analysis
smoking initiation 0.064 common-variant locus no MR -> candidate analysis
substance abuse 0.044 common-variant locus no MR -> candidate analysis
frozen shoulder 0.037 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 13 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=4.8e-11, LOEUF=1.38 — LoF-tolerant
GWAS Catalog 38 unique SNPs / 76 rows
ClinVar 141 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance