CausalSentinel

Protein Dossier — SIGLEC12 (Sialic acid-binding Ig-like lectin 12)

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
Non-cancer illness code self-reported: pneumothorax 0.313 0.105 0.00294 Wald ratio 1 cis NA
Multiple sclerosis -0.0862 0.0295 0.00353 Wald ratio 1 cis NA
Fasting proinsulin -0.024 0.00878 0.00639 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities -0.0553 0.0214 0.00968 Wald ratio 1 cis NA
Diagnoses - main ICD10: M54 Dorsalgia 0.05 0.0214 0.0196 Wald ratio 1 cis NA
Paget’s disease 0.149 0.0683 0.0297 Wald ratio 1 cis NA
Serum cystatin C (eGFRcys) -0.00488 0.00231 0.0344 Wald ratio 1 cis NA
Eye problems or disorders: Diabetes related eye disease -0.0821 0.0404 0.0421 Wald ratio 1 cis NA
Myocardial infarction 0.0249 0.0125 0.0465 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bone disorder 0.11 0.0556 0.0484 Wald ratio 1 cis NA
Non-cancer illness code self-reported: enlarged prostate 0.0459 0.0237 0.0523 Wald ratio 1 cis NA
Knee osteoarthritis -0.0644 0.0341 0.0593 Wald ratio 1 cis NA
…and 88 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

17 association rows across 11 traits (16 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
Blood protein levels 1e-371 rs1973095 5 GCST006585 no MR -> candidate analysis
Sialic acid-binding Ig-like lectin 12 levels (SIGLEC12.8352. 3e-366 rs3826667 1 GCST90242807 no MR -> candidate analysis
Sialic acid-binding Ig-like lectin 12:Ig-like V-type 2 domai 5e-323 rs3810114 1 GCST90421049 no MR -> candidate analysis
Circulating SIGLEC6 levels 7e-280 rs79814518 1 GCST90860512 no MR -> candidate analysis
SIGLEC5 protein levels 3e-201 rs2034889 1 GCST90470633 no MR -> candidate analysis
SIGLEC8 protein levels 5e-117 rs3810110 1 GCST90470636 no MR -> candidate analysis
Sialic acid-binding Ig-like lectin 12 level in Chronic kidne 7e-39 rs4801871 1 GCST90232810 no MR -> candidate analysis
Septin-6 protein levels (SomaScan ID:10037-98) 4e-33 rs968491 1 GCST90442431 no MR -> candidate analysis
Sialic acid-binding Ig-like lectin 6 levels 3e-21 rs75950899 2 GCST90161451 no MR -> candidate analysis
CD33 protein levels 5e-18 rs73051357 2 GCST90468625 no MR -> candidate analysis
Plasma calcium levels 6e-6 rs73049701 1 GCST90100541 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 58 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
placental abruption 0.33 common-variant locus no MR -> candidate analysis

Of the 1 rows above, 1 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=3e-12, LOEUF=1.03 — LoF-tolerant
GWAS Catalog 99 unique SNPs / 198 rows
ClinVar 151 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance