CausalSentinel

Protein Dossier — PPT1 (Palmitoyl-protein thioesterase 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
Pallidum volume 16.1 5.07 0.00154 Wald ratio 1 cis NA
Weight -0.0181 0.00615 0.00317 Wald ratio 1 cis NA
Body mass index (BMI) -0.0204 0.00696 0.00335 Wald ratio 1 cis NA
Non-cancer illness code self-reported: uterine fibroids 0.124 0.0498 0.013 Wald ratio 1 cis NA
Vascular or heart problems diagnosed by doctor: Angina -0.104 0.0434 0.017 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression -0.0733 0.0309 0.0177 Wald ratio 1 cis NA
Thalamus volume 37.5 16.6 0.0239 Wald ratio 1 cis NA
Cancer code self-reported: malignant melanoma 0.151 0.0682 0.0267 Wald ratio 1 cis NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0403 0.0195 0.0389 Wald ratio 1 cis NA
Diagnoses - main ICD10: K35 Acute appendicitis -0.242 0.13 0.0623 Wald ratio 1 cis NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] 0.096 0.0528 0.069 Wald ratio 1 cis NA
Non-cancer illness code self-reported: arthritis (nos) -0.175 0.0965 0.0698 Wald ratio 1 cis 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

14 association rows across 10 traits (13 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
Serum levels of protein PPT1 5e-150 rs6600314 2 GCST90090577 no MR -> candidate analysis
Palmitoyl-protein thioesterase 1 levels 5e-104 rs1800205 3 GCST90427718 no MR -> candidate analysis
Blood protein levels 1e-79 rs4660387 1 GCST006585 no MR -> candidate analysis
Palmitoyl-protein thioesterase 1 levels (PPT1.9244.27.3) 2e-46 rs7533094 2 GCST90242195 no MR -> candidate analysis
Height 2e-16 rs12061777 1 GCST90245848 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 4e-11 rs3122430 1 GCST90838669 no MR -> candidate analysis
Platelet count 2e-9 rs3122424 1 GCST90002402 no MR -> candidate analysis
Total PHF-tau (SNP x SNP interaction) 1e-8 rs12118846 x rs41497049 1 GCST010340 no MR -> candidate analysis
Body size or adipose distribution (multivariate analysis) 2e-8 rs6600317 1 GCST90624105 no MR -> candidate analysis
Refractive error 5e-8 rs6672277 1 GCST90841196 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 2312 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
neuronal ceroid lipofuscinosis 1 0.969 established (curated) no MR -> candidate analysis
neuronal ceroid lipofuscinosis 0.894 established (curated) no MR -> candidate analysis
hereditary disease 0.875 established (curated) no MR -> candidate analysis
retinitis pigmentosa 0.699 established (curated) no MR -> candidate analysis
juvenile neuronal ceroid lipofuscinosis 1 0.608 established (curated) no MR -> candidate analysis
adult neuronal ceroid lipofuscinosis 1 0.608 established (curated) no MR -> candidate analysis
infantile neuronal ceroid lipofuscinosis 1 0.608 established (curated) no MR -> candidate analysis
late infantile neuronal ceroid lipofuscinosis 1 0.608 established (curated) no MR -> candidate analysis
neurodevelopmental disorder with dysmorphic facies and distal limb anomalies 0.559 established (curated) no MR -> candidate analysis
Abnormality of the nervous system 0.438 established (curated) no MR -> candidate analysis
spastic ataxia 0.438 established (curated) no MR -> candidate analysis
streptococcal infection 0.337 common-variant locus no MR -> candidate analysis
Intellectual disability 0.228 established (curated) no MR -> candidate analysis

Of the 13 rows above, 13 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 (Palmitoyl-protein thioesterase 1)
gnomAD constraint pLI=0.0003, LOEUF=0.766 — LoF-tolerant
GWAS Catalog 27 unique SNPs / 54 rows
ClinVar 800 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance