CausalSentinel

Protein Dossier — PSAPL1 (Proactivator polypeptide-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
Anorexia nervosa 0.21 0.0801 0.00862 Wald ratio 1 cis NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis -0.163 0.063 0.00956 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate 0.13 0.0517 0.0121 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb -0.12 0.0485 0.0132 Wald ratio 1 cis NA
Knee and hip osteoarthritis 0.123 0.0523 0.0182 Wald ratio 1 cis NA
HbA1C 0.0193 0.00839 0.0212 Wald ratio 1 cis NA
Thyroid cancer -0.485 0.214 0.0238 Wald ratio 1 cis NA
Alcohol intake frequency -0.0187 0.00833 0.0247 Wald ratio 1 cis NA
Knee osteoarthritis 0.14 0.0644 0.0294 Wald ratio 1 cis NA
Amyotrophic lateral sclerosis -0.0859 0.0425 0.0432 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine -0.0825 0.0432 0.056 Wald ratio 1 cis NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.077 0.0409 0.0596 Wald ratio 1 cis NA
…and 92 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

11 association rows across 7 traits (11 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
PSAPL1 protein levels 3e-303 rs56269914 3 GCST90470350 no MR -> candidate analysis
Proactivator polypeptide-like 1 levels 7e-191 rs58274198 2 GCST90249429 no MR -> candidate analysis
Serum levels of protein PSAPL1 4e-110 rs74563302 1 GCST90090315 no MR -> candidate analysis
Proactivator polypeptide-like 1 levels (PSAPL1.8814.33.3) 3e-71 rs10023470 1 GCST90242354 no MR -> candidate analysis
CDSN protein levels 8e-35 rs75278193 1 GCST90468688 no MR -> candidate analysis
Circulating CDSN levels 1e-26 rs6850206 2 GCST90860191 no MR -> candidate analysis
Cerebrospinal fluid protein PSAPL1 levels 2e-10 rs58448418 1 GCST90943787 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 51 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
arthropathy 0.567 common-variant locus no MR -> candidate analysis
alcohol drinking 0.399 common-variant locus no MR -> candidate analysis
urolithiasis 0.33 common-variant locus no MR -> candidate analysis
nephrotic syndrome 0.203 common-variant locus no MR -> candidate analysis
bone Paget disease 0.203 common-variant locus no MR -> candidate analysis
tooth disorder 0.203 common-variant locus no MR -> candidate analysis
spinal cord injury 0.195 common-variant locus no MR -> candidate analysis
ulcerative colitis 0.169 common-variant locus no MR -> candidate analysis
ileostomy 0.169 common-variant locus no MR -> candidate analysis
pathological myopia 0.16 common-variant locus no MR -> candidate analysis
COVID-19 0.127 common-variant locus no MR -> candidate analysis
response to xenobiotic stimulus 0.123 common-variant locus no MR -> candidate analysis
poisoning 0.123 common-variant locus no MR -> candidate analysis
gastritis 0.104 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.078 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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=NA, LOEUF=NA — Constraint metrics missing; LoF tolerance cannot be judged.
GWAS Catalog 100 unique SNPs / 192 rows
ClinVar 224 records; 7 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance