CausalSentinel

Protein Dossier — PRELP (Prolargin)

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
Body mass index (BMI) 0.00819 0.00265 0.00196 Wald ratio 1 trans NA
Diagnoses - main ICD10: K80 Cholelithiasis 0.0538 0.0175 0.00206 Wald ratio 1 trans NA
Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis 0.0884 0.0355 0.0128 Wald ratio 1 trans NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.0699 0.0294 0.0174 Wald ratio 1 trans NA
Non-cancer illness code self-reported: osteoarthritis -0.0185 0.00902 0.0402 Wald ratio 1 trans NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.0703 0.0343 0.0406 Wald ratio 1 trans NA
Pulse rate 0.00933 0.00467 0.0459 Wald ratio 1 trans NA
Diagnoses - main ICD10: L03 Cellulitis 0.0553 0.0279 0.0475 Wald ratio 1 trans NA
Non-cancer illness code self-reported: iron deficiency anaemia -0.0765 0.0392 0.0511 Wald ratio 1 trans NA
Fracture resulting from simple fall 0.0132 0.00688 0.0552 Wald ratio 1 trans NA
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.0642 0.0338 0.0575 Wald ratio 1 trans NA
Eye problems or disorders: Diabetes related eye disease 0.0605 0.0319 0.0578 Wald ratio 1 trans NA
…and 54 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

40 association rows across 26 traits (35 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 PRELP levels 3e-1687 rs41313926 4 GCST90859791 no MR -> candidate analysis
Ankyrin-2 levels 5e-265 rs41313926 6 GCST90246511 no MR -> candidate analysis
OPTC protein levels 4e-104 rs10217817 2 GCST90470128 no MR -> candidate analysis
Ankyrin-2 levels (ANK2.7624.19.3) 1e-91 rs41313926 1 GCST90240295 no MR -> candidate analysis
Circulating OPTC levels 5e-79 rs3766907 1 GCST90860578 no MR -> candidate analysis
Keratocan levels 5e-62 rs879446 2 GCST90248183 no MR -> candidate analysis
CHIT1 protein levels 2e-42 rs544579097 4 GCST90468744 no MR -> candidate analysis
Potassium voltage-gated channel subfamily E regulatory beta 2e-39 rs41313926 1 GCST90249191 no MR -> candidate analysis
PRELP protein levels 5e-35 rs74599912 1 GCST90470321 no MR -> candidate analysis
Prolow-density lipoprotein receptor-related protein 1 levels 6e-31 rs41313926 2 GCST90421198 no MR -> candidate analysis
Serum levels of protein KERA 7e-30 rs10920636 1 GCST90086440 no MR -> candidate analysis
Cerebrospinal fluid protein PRELP levels 9e-27 rs41313926 1 GCST90944512 no MR -> candidate analysis
…and 14 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 210 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
osteoarthritis, hip 0.509 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.393 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.273 common-variant locus no MR -> candidate analysis
arthropathy 0.192 common-variant locus no MR -> candidate analysis
liver disorder 0.191 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.113 common-variant locus no MR -> candidate analysis

Of the 6 rows above, 6 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=0.00013, LOEUF=1.06 — LoF-tolerant
GWAS Catalog 68 unique SNPs / 136 rows
ClinVar 79 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance