CausalSentinel

Protein Dossier — TPST1 (Protein-tyrosine sulfotransferase 1)

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
Weight -0.0378 0.00991 1.35e-04 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.0368 0.0115 0.00135 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine 0.15 0.0561 0.00752 Wald ratio 1 cis NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] -0.357 0.137 0.00898 Wald ratio 1 cis NA
Happiness 0.0335 0.0139 0.0158 Wald ratio 1 cis NA
Triglycerides 0.0532 0.022 0.0159 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.0233 0.00972 0.0164 Wald ratio 1 cis NA
Rheumatoid arthritis -0.17 0.0746 0.0231 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0204 0.00922 0.0268 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.222 0.106 0.0361 Wald ratio 1 cis NA
Serum cystatin C (eGFRcys) 0.0177 0.00865 0.0404 Wald ratio 1 cis NA
Mean cell volume 0.233 0.114 0.0408 Wald ratio 1 cis NA
…and 97 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

18 association rows across 10 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
Protein-tyrosine sulfotransferase 1 levels 4e-64 rs12537083 1 GCST90249185 no MR -> candidate analysis
Argininosuccinate lyase levels 2e-31 rs4145009 1 GCST90246581 no MR -> candidate analysis
White blood cell count 9e-25 rs12540307 8 GCST90662906 no MR -> candidate analysis
Height (baseline) 2e-15 rs4291144 1 GCST90565843 no MR -> candidate analysis
Bone mineral density mean 7e-14 rs75734022 1 GCST90321120 no MR -> candidate analysis
Smoking initiation 3e-13 rs62468710 1 GCST90243968 no MR -> candidate analysis
Neutrophil count 3e-12 rs12540307 1 GCST90018968 no MR -> candidate analysis
Triglyceride levels 7e-10 rs9969301 1 GCST90662893 no MR -> candidate analysis
Gout 1e-7 rs4149458 2 GCST001356 MR: beta=0.0934, p=0.28 (cis)
Hospitalization rate in serious mental illnesses 7e-6 rs146187962 1 GCST90559268 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 77 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
smoking initiation 0.254 common-variant locus no MR -> candidate analysis
poisoning 0.135 common-variant locus no MR -> candidate analysis
Alzheimer disease 0.064 common-variant locus no MR -> candidate analysis

Of the 3 rows above, 3 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=0.00039, LOEUF=0.835 — LoF-tolerant
GWAS Catalog 22 unique SNPs / 42 rows
ClinVar 71 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance