CausalSentinel

Protein Dossier — SHISA3 (Protein shisa-3 homolog)

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
Eczema -0.608 0.105 6.92e-09 Wald ratio 1 trans 0.283
Non-cancer illness code self-reported: asthma -0.258 0.0535 1.38e-06 Wald ratio 1 trans NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.179 0.0374 1.79e-06 Wald ratio 1 trans NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.199 0.0447 8.10e-06 Wald ratio 1 trans NA
Pulse rate -0.0839 0.0259 0.00118 Wald ratio 1 trans NA
Heel bone mineral density (BMD) T-score automated -0.0493 0.0191 0.00967 Wald ratio 1 trans NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux 0.157 0.0608 0.00979 Wald ratio 1 trans NA
Primary sclerosing cholangitis -0.542 0.218 0.0128 Wald ratio 1 trans NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis -0.316 0.133 0.018 Wald ratio 1 trans NA
Thalamus volume 84.3 37.7 0.0251 Wald ratio 1 trans NA
Weight 0.0274 0.013 0.0348 Wald ratio 1 trans NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.284 0.135 0.0352 Wald ratio 1 trans NA
…and 59 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

38 association rows across 23 traits (15 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
Adolescent idiopathic scoliosis 5e-13 rs7664918 1 GCST006287 no MR -> candidate analysis
Cigarettes smoked per day 3e-11 rs10004736 3 GCST90243987 no MR -> candidate analysis
Refractive error 2e-10 rs13119304 3 GCST90841196 no MR -> candidate analysis
Free Cholesterol to Cholesteryl Esters in Large HDL ratio 3e-10 rs75236220 1 GCST90827800 no MR -> candidate analysis
Estimated glomerular filtration rate 2e-9 rs11722932 1 GCST90019506 no MR -> candidate analysis
Height 2e-9 rs6819984 1 GCST90662911 no MR -> candidate analysis
Serum creatinine levels 3e-9 rs74464322 1 GCST90018979 no MR -> candidate analysis
Creatinine levels 5e-9 rs11722932 2 GCST90019502 no MR -> candidate analysis
Facial appearance 8e-9 rs60442375 1 GCST90128425 no MR -> candidate analysis
Memory decline (excluding comorbidities) 2e-8 rs6848524 6 GCST90448862 no MR -> candidate analysis
Longevity 3e-7 rs1487614 1 GCST003425 no MR -> candidate analysis
Systolic blood pressure (baseline) 4e-7 rs112586322 2 GCST011891 no MR -> candidate analysis
…and 11 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 60 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
facial morphology 0.513 common-variant locus no MR -> candidate analysis
placenta praevia 0.44 common-variant locus no MR -> candidate analysis
placental abruption 0.12 common-variant locus no MR -> candidate analysis
self-injurious ideation 0.093 common-variant locus no MR -> candidate analysis
secondary malignant neoplasm 0.077 common-variant locus no MR -> candidate analysis
connective tissue disorder 0.046 common-variant locus no MR -> candidate analysis
stroke disorder 0.04 common-variant locus no MR -> candidate analysis
alcohol drinking 0.04 common-variant locus no MR -> candidate analysis
adolescent idiopathic scoliosis 0.039 common-variant locus no MR -> candidate analysis

Of the 9 rows above, 9 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=6.4e-05, LOEUF=1.2 — LoF-tolerant
GWAS Catalog 51 unique SNPs / 65 rows
ClinVar 62 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance