CausalSentinel

Protein Dossier — VSIR (V-type immunoglobulin domain-containing suppressor of T-cell activation)

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
Body fat 0.0795 0.0274 0.00367 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma 0.0865 0.0324 0.00768 Wald ratio 1 cis NA
HOMA-B 0.0444 0.017 0.00909 Wald ratio 1 cis NA
Diagnoses - main ICD10: B37 Candidiasis 0.784 0.306 0.0104 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.035 0.0163 0.0322 Wald ratio 1 cis NA
Vascular or heart problems diagnosed by doctor: Angina 0.133 0.0622 0.0328 Wald ratio 1 cis NA
HOMA-IR 0.0444 0.0211 0.0353 Wald ratio 1 cis NA
Lumbar spine bone mineral density -0.0936 0.0452 0.0386 Wald ratio 1 cis NA
Schizophrenia -0.108 0.054 0.0448 Wald ratio 1 cis NA
Diagnoses - main ICD10: K35 Acute appendicitis 0.277 0.141 0.0488 Wald ratio 1 cis NA
HDL cholesterol 0.0481 0.0248 0.0523 Wald ratio 1 cis NA
Coronary heart disease 0.0869 0.0467 0.0625 Wald ratio 1 cis NA
…and 81 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

100 association rows across 52 traits (97 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
V-type immunoglobulin domain-containing suppressor of T-cell 2e-559 rs10762476 4 GCST90250167 no MR -> candidate analysis
DIABLO/VSIR protein level ratio 1e-164 rs9415041 1 GCST90314470 no MR -> candidate analysis
Circulating CXCL16 levels 5e-88 rs748113 1 GCST90859949 no MR -> candidate analysis
Lymphocyte count 2e-65 rs748113 6 GCST90002316 no MR -> candidate analysis
CXCL16 protein levels 8e-65 rs748113 1 GCST90468928 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 7e-61 rs748113 2 GCST90838669 no MR -> candidate analysis
Lymphocyte count (UKB data field 30120) 8e-48 rs748113 1 GCST90468082 no MR -> candidate analysis
White blood cell count 2e-46 rs3747869 13 GCST90662906 no MR -> candidate analysis
Platelet receptor Gi24 levels 2e-36 rs12415873 3 GCST90161317 no MR -> candidate analysis
white blood cell count (WBC, mean, inv-norm transformed) 2e-27 rs3747869 2 GCST90476454 no MR -> candidate analysis
Monocyte count 6e-27 rs7919533 8 GCST90002344 no MR -> candidate analysis
C-X-C motif chemokine 16 levels 7e-26 rs748113 2 GCST90247204 no MR -> candidate analysis
…and 40 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 368 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
hypothyroidism 0.494 common-variant locus MR: beta=-0.0631, p=0.293 (cis)
alcohol drinking 0.47 common-variant locus no MR -> candidate analysis
ulcerative colitis 0.195 common-variant locus no MR -> candidate analysis

Of the 3 rows above, 2 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 0 known modulators (V-type immunoglobulin domain-containing suppressor of T-cell activation)
gnomAD constraint pLI=0.93, LOEUF=0.547 — LoF-INTOLERANT
GWAS Catalog 88 unique SNPs / 176 rows
ClinVar 48 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance