CausalSentinel

Protein Dossier — PLEKHA7 (Pleckstrin homology domain-containing family A member 7)

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: hypertension 0.0827 0.0213 1.03e-04 Wald ratio 1 cis NA
Systolic blood pressure automated reading 0.0526 0.0139 1.53e-04 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0417 0.0139 0.00267 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt 0.288 0.114 0.0117 Wald ratio 1 cis NA
Platelet count 6.36 2.56 0.0129 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia -0.27 0.11 0.0142 Wald ratio 1 cis NA
Myocardial infarction 0.133 0.0569 0.0192 Wald ratio 1 cis NA
Fasting glucose 0.0434 0.0195 0.0263 Wald ratio 1 cis NA
Rheumatoid arthritis 0.176 0.0795 0.0265 Wald ratio 1 cis NA
Diagnoses - main ICD10: R11 Nausea and vomiting 0.346 0.157 0.0281 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis 0.0877 0.0416 0.035 Wald ratio 1 cis NA
Pallidum volume 22.5 10.7 0.0366 Wald ratio 1 cis NA
…and 84 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

137 association rows across 76 traits (102 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
Pleckstrin homology domain-containing family A member 7 leve 5e-694 rs425325 4 GCST90249021 no MR -> candidate analysis
Bone mineral density mean 3e-77 rs112467382 1 GCST90321120 no MR -> candidate analysis
NUCB2 protein levels 2e-47 rs72865761 7 GCST90470101 no MR -> candidate analysis
Reticulocyte fraction of red cells 3e-46 rs17472529 1 GCST90002406 no MR -> candidate analysis
Reticulocyte count 2e-37 rs17472529 1 GCST90002405 no MR -> candidate analysis
Mean corpuscular hemoglobin 5e-35 rs17472529 1 GCST90002390 no MR -> candidate analysis
High light scatter reticulocyte percentage of red cells 2e-29 rs17472529 1 GCST90002386 no MR -> candidate analysis
NCR3LG1 protein levels 6e-27 rs77255250 4 GCST90470010 no MR -> candidate analysis
High light scatter reticulocyte count 5e-25 rs17472529 1 GCST90002385 no MR -> candidate analysis
Vertex-wise sulcal depth 2e-24 rs7947897 1 GCST90095129 no MR -> candidate analysis
Primary open angle glaucoma (multi-trait analysis) 2e-24 rs4141194 1 GCST90310211 no MR -> candidate analysis
Retinal thickness (pixel 63_91) 8e-22 rs12575487 1 GCST90527987 no MR -> candidate analysis
…and 64 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 141 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
glaucoma 0.776 common-variant locus no MR -> candidate analysis
open-angle glaucoma 0.776 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.747 common-variant locus no MR -> candidate analysis
cleft lip 0.603 established (curated) no MR -> candidate analysis
alcohol drinking 0.655 common-variant locus no MR -> candidate analysis
primary angle-closure glaucoma 0.601 common-variant locus no MR -> candidate analysis
essential hypertension 0.589 common-variant locus no MR -> candidate analysis
Back pain 0.524 common-variant locus no MR -> candidate analysis
ovarian dysfunction 0.513 common-variant locus no MR -> candidate analysis
pyogenic granuloma 0.512 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.498 common-variant locus no MR -> candidate analysis
response to xenobiotic stimulus 0.478 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.466 common-variant locus no MR -> candidate analysis
bilirubin metabolism disease 0.428 common-variant locus no MR -> candidate analysis
smoking initiation 0.378 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 0 known modulators (Pleckstrin homology domain-containing family A member 7)
gnomAD constraint pLI=1.4e-19, LOEUF=0.72 — LoF-tolerant
GWAS Catalog 115 unique SNPs / 247 rows
ClinVar 311 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance