CausalSentinel

Protein Dossier — PPIL1 (Peptidyl-prolyl cis-trans isomerase-like 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
Cigarettes smoked per day 0.508 0.217 0.0192 Wald ratio 1 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.0963 0.0412 0.0193 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine 0.0833 0.0375 0.0262 Wald ratio 1 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain -0.0751 0.0367 0.0408 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension -0.0244 0.0123 0.0474 Wald ratio 1 cis NA
Diagnoses - main ICD10: J33 Nasal polyp -0.264 0.136 0.0527 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0172 0.0091 0.0584 Wald ratio 1 cis NA
Fasting glucose -0.0154 0.00832 0.0646 Wald ratio 1 cis NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages -0.231 0.126 0.0657 Wald ratio 1 cis NA
Pulse rate -0.0226 0.0125 0.0704 Wald ratio 1 cis NA
Body mass index (BMI) 0.0125 0.00704 0.0758 Wald ratio 1 cis NA
Forearm bone mineral density 0.0747 0.0422 0.077 Wald ratio 1 cis NA
…and 69 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

32 association rows across 25 traits (27 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
Peptidyl-prolyl cis-trans isomerase-like 1 levels 1e-451 rs12194408 1 GCST90248953 no MR -> candidate analysis
heart rate (HR, minimum, inv-normal transformed) 5e-66 rs236352 3 GCST90476341 no MR -> candidate analysis
Peptidyl-prolyl cis-trans isomerase-like 1 levels (PPIL1.988 2e-55 rs12194408 1 GCST90242223 no MR -> candidate analysis
Pulse rate (UKB data field 102) 1e-32 rs236349 1 GCST90468177 no MR -> candidate analysis
Heart rate variability traits (SDNN) 2e-28 rs236349 2 GCST004734 no MR -> candidate analysis
Height 7e-25 rs2071822 1 GCST90245848 no MR -> candidate analysis
heart rate (HR, mean, inv-normal transformed) 1e-24 rs236352 2 GCST90476338 no MR -> candidate analysis
Heart rate variability traits (RMSSD) 6e-20 rs236349 2 GCST004733 no MR -> candidate analysis
Heart rate variability (standard deviation of normal-to-norm 9e-20 rs236349 1 GCST90281265 no MR -> candidate analysis
Heart rate variability (corrected standard deviation of norm 4e-19 rs236349 1 GCST90281266 no MR -> candidate analysis
Heart rate variability (corrected root mean square of succes 5e-17 rs236349 1 GCST90281264 no MR -> candidate analysis
Heart rate variability (root mean square of successive diffe 6e-16 rs236349 1 GCST90281263 no MR -> candidate analysis
…and 13 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 490 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
pontocerebellar hypoplasia, type 14 0.907 established (curated) no MR -> candidate analysis
pontocerebellar hypoplasia 0.66 established (curated) no MR -> candidate analysis
Non-syndromic pontocerebellar hypoplasia 0.66 established (curated) no MR -> candidate analysis
hypothyroidism 0.549 common-variant locus MR: beta=-0.0245, p=0.445 (cis)
neurodevelopmental disorder 0.438 established (curated) no MR -> candidate analysis
major depressive disorder 0.316 common-variant locus no MR -> candidate analysis
hereditary disease 0.309 established (curated) no MR -> candidate analysis
cardiac arrhythmia 0.17 common-variant locus no MR -> candidate analysis

Of the 8 rows above, 7 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 (Peptidyl-prolyl cis-trans isomerase-like 1)
gnomAD constraint pLI=0.00026, LOEUF=1.13 — LoF-tolerant
GWAS Catalog 64 unique SNPs / 128 rows
ClinVar 56 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance