CausalSentinel

Protein Dossier — SULF2 (Extracellular sulfatase Sulf-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
Non-cancer illness code self-reported: gout 0.569 0.0578 7.21e-23 Wald ratio 1 trans 0.981
Urate 0.278 0.0286 3.11e-22 Wald ratio 1 trans NA
Triglycerides 0.119 0.0169 1.77e-12 Wald ratio 1 trans 0.991
HDL cholesterol -0.118 0.0178 3.26e-11 Wald ratio 1 trans 0.992
Serum creatinine (eGFRcrea) -0.0239 0.00434 3.80e-08 Wald ratio 1 trans 0.992
Creatinine (enzymatic) in urine -0.0572 0.0116 8.59e-07 Wald ratio 1 trans NA
Potassium in urine -0.0554 0.0123 6.78e-06 Wald ratio 1 trans NA
Ferritin 0.176 0.0482 2.64e-04 Wald ratio 1 trans NA
Non-cancer illness code self-reported: asthma -0.139 0.0391 3.87e-04 Wald ratio 1 trans NA
LDL cholesterol 0.0664 0.0191 5.07e-04 Wald ratio 1 trans NA
Haemoglobin concentration -0.115 0.0339 7.13e-04 Wald ratio 1 trans NA
Neuroticism 0.0564 0.0174 0.00115 Wald ratio 1 trans NA
…and 114 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

177 association rows across 126 traits (156 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
Phospholipids in HDL 2e-47 rs4239651 2 GCST90501117 no MR -> candidate analysis
Total Lipids in HDL 6e-46 rs4239651 2 GCST90501115 no MR -> candidate analysis
High density lipoprotein cholesterol levels 2e-44 rs4239651 7 GCST90239649 no MR -> candidate analysis
Concentration of medium HDL particles 4e-44 rs4239651 3 GCST90501189 no MR -> candidate analysis
Free cholesterol in medium HDL 4e-43 rs4239651 2 GCST90501186 no MR -> candidate analysis
Apolipoprotein A1 levels 2e-42 rs4239651 8 GCST90501098 no MR -> candidate analysis
Total lipids in medium HDL 2e-42 rs4239651 2 GCST90501188 no MR -> candidate analysis
Cholesterol in Medium HDL 6e-42 rs4239651 2 GCST90501182 no MR -> candidate analysis
Phospholipids in medium HDL 1e-41 rs4239651 2 GCST90501190 no MR -> candidate analysis
Cholesteryl Esters in Medium HDL 7e-41 rs4239651 2 GCST90501184 no MR -> candidate analysis
Free Cholesterol in HDL 5e-38 rs4239651 1 GCST90501114 no MR -> candidate analysis
Phospholipids to Total Lipids in Small HDL percentage 1e-32 rs4239651 2 GCST90501243 no MR -> candidate analysis
…and 114 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 365 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
osteoarthritis, knee 0.748 common-variant locus MR: beta=-0.253, p=0.0641 (trans)
alcohol drinking 0.684 common-variant locus no MR -> candidate analysis
smoking initiation 0.569 common-variant locus no MR -> candidate analysis
liver disorder 0.539 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.482 common-variant locus no MR -> candidate analysis
osteoarthritis 0.461 common-variant locus MR: beta=-0.253, p=0.0641 (trans)
osteoarthritis, hip 0.461 common-variant locus MR: beta=-0.128, p=0.276 (trans)
total knee arthroplasty 0.461 common-variant locus no MR -> candidate analysis
squamous cell carcinoma 0.43 common-variant locus no MR -> candidate analysis
arthropathy 0.43 common-variant locus no MR -> candidate analysis
head injury 0.406 common-variant locus no MR -> candidate analysis
Sjogren syndrome 0.364 common-variant locus no MR -> candidate analysis
non-Hodgkin lymphoma 0.363 common-variant locus no MR -> candidate analysis
lymphatic system cancer 0.363 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.345 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 12 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=2.2e-05, LOEUF=0.608 — LoF-tolerant
GWAS Catalog 61 unique SNPs / 121 rows
ClinVar 188 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance