CausalSentinel

Protein Dossier — PEAR1 (Platelet endothelial aggregation receptor 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
Systolic blood pressure automated reading 0.0405 0.0112 3.17e-04 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0345 0.0113 0.00218 Wald ratio 1 cis NA
Serum cystatin C (eGFRcys) 0.0234 0.00898 0.00932 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0459 0.0179 0.0104 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis -0.214 0.0889 0.0162 Wald ratio 1 cis NA
Height 0.0364 0.0153 0.0172 Wald ratio 1 cis NA
Potassium in urine -0.0265 0.0112 0.0177 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis -0.0942 0.0405 0.02 Wald ratio 1 cis NA
Total cholesterol -0.058 0.0256 0.0236 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine -0.0231 0.0105 0.0282 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0629 0.0305 0.0395 Wald ratio 1 cis NA
Non-cancer illness code self-reported: uterine fibroids 0.156 0.0764 0.0407 Wald ratio 1 cis NA
…and 107 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

207 association rows across 100 traits (202 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
neutrophil (absolute count, maximum, inv-norm transformed) 1e-323 rs2768762 1 GCST90475525 no MR -> candidate analysis
Mean platelet volume during third trimester of pregnancy 1e-315 rs12041331 4 GCST90302231 no MR -> candidate analysis
PEAR1 protein levels 3e-232 rs4661012 4 GCST90470204 no MR -> candidate analysis
Circulating PEAR1 levels 5e-229 rs4661012 4 GCST90860639 no MR -> candidate analysis
ENG/PEAR1 protein level ratio 3e-188 rs11264581 1 GCST90314649 no MR -> candidate analysis
Platelet count during third trimester of pregnancy 4e-163 rs12041331 3 GCST90302226 no MR -> candidate analysis
Platelet count at delivery 9e-154 rs12048392 2 GCST90302227 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 5e-153 rs12041331 3 GCST90468087 no MR -> candidate analysis
Mean platelet volume at delivery 1e-147 rs12041331 3 GCST90302232 no MR -> candidate analysis
Mean platelet volume 1e-145 rs12041331 13 GCST90002349 no MR -> candidate analysis
White blood cell count 4e-140 rs2768762 2 GCST90026503 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 7e-132 rs12566888 4 GCST90838671 no MR -> candidate analysis
…and 88 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 145 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
platelet aggregation 0.75 common-variant locus no MR -> candidate analysis
Thrombocytopenia 0.584 common-variant locus no MR -> candidate analysis
Decreased total leukocyte count 0.565 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.545 common-variant locus no MR -> candidate analysis
alcohol drinking 0.175 common-variant locus no MR -> candidate analysis

Of the 5 rows above, 5 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=5.6e-33, LOEUF=1.01 — LoF-tolerant
GWAS Catalog 111 unique SNPs / 242 rows
ClinVar 210 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx 15 clinical annotations across 4 drugs

Caveats declared by the tools

Sources

Provenance