CausalSentinel

Protein Dossier — PLXNB2 (Plexin-B2)

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
Heel bone mineral density (BMD) T-score automated -0.0337 0.00599 1.88e-08 Wald ratio 1 cis 0.963
Non-cancer illness code self-reported: hypertension -0.0307 0.00813 1.58e-04 Wald ratio 1 cis NA
Systolic blood pressure automated reading -0.0159 0.00473 7.67e-04 Wald ratio 1 cis NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0499 0.0156 0.00141 Wald ratio 1 cis NA
Diagnoses - main ICD10: H25 Senile cataract 0.143 0.0457 0.00171 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0397 0.0132 0.00258 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.133 0.0471 0.00477 Wald ratio 1 cis NA
Cancer code self-reported: prostate cancer 0.124 0.0479 0.00965 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine 0.0749 0.0302 0.0132 Wald ratio 1 cis NA
Weight 0.0101 0.00408 0.0138 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis 0.0828 0.0342 0.0154 Wald ratio 1 cis NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.0818 0.0347 0.0183 Wald ratio 1 cis NA
…and 74 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

95 association rows across 67 traits (79 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 PLXNB2 levels 3e-2637 rs11547731 7 GCST90860422 no MR -> candidate analysis
Plexin-B2 levels 3e-502 rs28578714 6 GCST90249039 no MR -> candidate analysis
Plexin-B2 levels (PLXNB2.9216.100.3) 4e-116 rs28573806 1 GCST90242299 no MR -> candidate analysis
Plexin-B2 level in Chronic kidney disease with hypertension 6e-103 rs28379706 1 GCST90233009 no MR -> candidate analysis
Serum levels of protein PLXNB2 8e-102 rs28379706 1 GCST90090558 no MR -> candidate analysis
PLXNB2 protein levels 1e-77 rs58705604 4 GCST90470266 no MR -> candidate analysis
R-spondin-2 protein levels (SomaScan ID:10855-55) 8e-55 rs28379706 1 GCST90443179 no MR -> candidate analysis
Platelet crit (UKB data field 30090) 6e-36 rs73188911 1 GCST90468096 no MR -> candidate analysis
Mean reticulocyte volume (UKB data field 30260) 1e-32 rs117265627 1 GCST90468088 no MR -> candidate analysis
Mean sphered cell volume (UKB data field 30270) 1e-29 rs117265627 1 GCST90468089 no MR -> candidate analysis
Mean corpuscular volume (UKB data field 30040) 7e-28 rs117265627 1 GCST90468086 no MR -> candidate analysis
Cerebrospinal fluid protein PLXNB2 levels 1e-22 rs111925803 1 GCST90944865 no MR -> candidate analysis
…and 55 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 1366 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
cutaneous melanoma 0.78 common-variant locus no MR -> candidate analysis
hair color 0.717 common-variant locus no MR -> candidate analysis
cancer 0.584 common-variant locus MR: beta=-0.0307, p=1.58e-04 (cis)
hypertensive disorder 0.585 common-variant locus no MR -> candidate analysis
vein disorder 0.4 common-variant locus no MR -> candidate analysis
lymphatic system disorder 0.4 common-variant locus no MR -> candidate analysis
Varicose veins 0.362 common-variant locus MR: beta=0.048, p=0.119 (cis)
arthropathy 0.182 common-variant locus no MR -> candidate analysis
obesity disorder 0.156 common-variant locus no MR -> candidate analysis

Of the 9 rows above, 7 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=0.021, LOEUF=0.502 — LoF-tolerant
GWAS Catalog 110 unique SNPs / 256 rows
ClinVar 579 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance