CausalSentinel

Protein Dossier — PSAP (Prosaposin)

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
Diagnoses - main ICD10: R55 Syncope and collapse 0.128 0.042 0.00229 Wald ratio 1 cis NA
Body mass index (BMI) 0.0128 0.00449 0.00427 Wald ratio 1 cis NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.133 0.0548 0.0152 Wald ratio 1 cis NA
Non-cancer illness code self-reported: retinal detachment -0.237 0.1 0.0184 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] -0.0819 0.0351 0.0198 Wald ratio 1 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.0603 0.0272 0.0266 Wald ratio 1 cis NA
Rheumatoid arthritis 0.0659 0.0299 0.0275 Wald ratio 1 cis NA
Depressive symptoms -0.0178 0.00808 0.0278 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate 0.0936 0.0426 0.0281 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis 0.0853 0.0389 0.0282 Wald ratio 1 cis NA
Fracture resulting from simple fall 0.0249 0.0115 0.0308 Wald ratio 1 cis NA
Diagnoses - main ICD10: M54 Dorsalgia 0.068 0.0326 0.0369 Wald ratio 1 cis NA
…and 73 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

74 association rows across 46 traits (58 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
Circulating GRN levels 2e-237 rs12248615 1 GCST90859928 no MR -> candidate analysis
PSAP protein levels 1e-202 rs12253310 3 GCST90470351 no MR -> candidate analysis
Serum levels of protein PSAP 1e-195 rs7899959 3 GCST90089295 no MR -> candidate analysis
Leukocyte immunoglobulin-like receptor subfamily B member 4 1e-188 rs55688436 3 GCST90248304 no MR -> candidate analysis
Serum levels of protein LILRB4 8e-180 rs41306532 3 GCST90089435 no MR -> candidate analysis
Prosaposin levels 5e-165 rs2394843 4 GCST90249117 no MR -> candidate analysis
Blood protein levels 4e-122 rs7086891 2 GCST006585 no MR -> candidate analysis
Granulins levels 2e-83 rs4747203 4 GCST90247801 no MR -> candidate analysis
GRN protein levels 6e-76 rs11000064 3 GCST90469404 no MR -> candidate analysis
CD83 protein levels 6e-41 rs7869 2 GCST90468652 no MR -> candidate analysis
Circulating CD83 levels (id: OID00841_OID20565) 2e-40 rs55688436 1 GCST90860166 no MR -> candidate analysis
VSIR protein levels 7e-40 rs11000044 4 GCST90471053 no MR -> candidate analysis
…and 34 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 3582 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
Gaucher disease due to saposin C deficiency 0.84 established (curated) no MR -> candidate analysis
Krabbe disease due to saposin A deficiency 0.821 established (curated) no MR -> candidate analysis
combined PSAP deficiency 0.849 established (curated) no MR -> candidate analysis
Krabbe disease 0.875 established (curated) no MR -> candidate analysis
Parkinson disease 0.547 established (curated) no MR -> candidate analysis
metachromatic leukodystrophy 0.941 established (curated) no MR -> candidate analysis
Gaucher disease 0.608 established (curated) no MR -> candidate analysis
hereditary disease 0.743 established (curated) no MR -> candidate analysis
metachromatic leukodystrophy, juvenile form 0.608 established (curated) no MR -> candidate analysis
metachromatic leukodystrophy, late infantile form 0.608 established (curated) no MR -> candidate analysis
metachromatic leukodystrophy, adult form 0.608 established (curated) no MR -> candidate analysis
infantile Krabbe disease 0.608 established (curated) no MR -> candidate analysis
Hereditary late-onset Parkinson disease 0.547 established (curated) no MR -> candidate analysis
late-onset Parkinson disease 0.547 established (curated) no MR -> candidate analysis
pericarditis 0.406 common-variant locus MR: beta=-0.273, p=0.499 (cis)

Of the 15 rows above, 14 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 (Prosaposin)
gnomAD constraint pLI=0.83, LOEUF=0.529 — LoF-tolerant
GWAS Catalog 112 unique SNPs / 222 rows
ClinVar 1031 records; 13 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance