CausalSentinel

Protein Dossier — LRP12 (Low-density lipoprotein receptor-related protein 12)

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
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux 0.195 0.0564 5.32e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pneumothorax 0.877 0.327 0.0073 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse 0.346 0.139 0.013 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia 0.18 0.0729 0.0135 Wald ratio 1 cis NA
Pallidum volume -25.9 11.4 0.0231 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0515 0.023 0.0252 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine 0.0301 0.0136 0.0268 Wald ratio 1 cis NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate 0.284 0.134 0.0344 Wald ratio 1 cis NA
Putamen volume -75.1 35.7 0.0353 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis 0.193 0.095 0.0425 Wald ratio 1 cis NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0882 0.0441 0.0455 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] 0.173 0.0868 0.0465 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

4 association rows across 3 traits (2 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
Educational attainment 5e-10 rs3134530 1 GCST90105038 no MR -> candidate analysis
Type 2 diabetes 3e-8 rs28627996 2 GCST90492734 no MR -> candidate analysis
Facial morphology (factor 22) 3e-6 rs79944793 1 GCST004326 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 130 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
oculopharyngodistal myopathy 0.608 established (curated) no MR -> candidate analysis
oculopharyngodistal myopathy 1 0.617 established (curated) no MR -> candidate analysis
amyotrophic lateral sclerosis 28 0.617 established (curated) no MR -> candidate analysis
hypertensive disorder 0.661 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.56 common-variant locus no MR -> candidate analysis
alcohol drinking 0.55 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.534 common-variant locus no MR -> candidate analysis
respiratory tract infectious disorder 0.482 common-variant locus no MR -> candidate analysis
Abnormal abdomen morphology 0.419 common-variant locus no MR -> candidate analysis
atrial flutter 0.4 common-variant locus no MR -> candidate analysis
Increased blood pressure 0.396 common-variant locus no MR -> candidate analysis
placenta praevia 0.396 common-variant locus no MR -> candidate analysis
cardiovascular disorder 0.364 common-variant locus no MR -> candidate analysis
cerebrovascular disorder 0.365 common-variant locus no MR -> candidate analysis
open-angle glaucoma 0.361 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=1, LOEUF=0.332 — LoF-INTOLERANT
GWAS Catalog 79 unique SNPs / 125 rows
ClinVar 175 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance