CausalSentinel

Protein Dossier — PLXNA1 (Plexin-A1)

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
Forced vital capacity (FVC) -0.0494 0.0117 2.27e-05 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine 0.0504 0.0136 2.13e-04 Wald ratio 1 cis NA
Potassium in urine 0.0503 0.0144 4.85e-04 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.0421 0.0123 6.30e-04 Wald ratio 1 cis NA
LDL cholesterol 0.0945 0.0313 0.00255 Wald ratio 1 cis NA
Total cholesterol 0.089 0.0308 0.00382 Wald ratio 1 cis NA
Childhood intelligence -0.187 0.0775 0.0156 Wald ratio 1 cis NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.361 0.151 0.0167 Wald ratio 1 cis NA
Sodium in urine 0.0334 0.014 0.0169 Wald ratio 1 cis NA
Internalizing problems -0.302 0.13 0.0203 Wald ratio 1 cis NA
Amygdala volume 31.5 13.7 0.0215 Wald ratio 1 cis NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.775 0.361 0.0318 Wald ratio 1 cis NA
…and 102 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

26 association rows across 24 traits (19 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
Bone mineral density mean 1e-300 rs147981744 1 GCST90321120 no MR -> candidate analysis
Youthful appearance (self-reported) 1e-51 rs61263161 1 GCST011011 no MR -> candidate analysis
Plexin-A1 levels 1e-50 rs7644947 1 GCST90249037 no MR -> candidate analysis
Circulating SEMA3F levels 3e-42 rs9822602 1 GCST90860355 no MR -> candidate analysis
SEMA3F protein levels 2e-29 rs10934798 1 GCST90470570 no MR -> candidate analysis
Plexin-A1 levels (PLXNA1.9005.16.3) 2e-21 rs35154032 1 GCST90242298 no MR -> candidate analysis
Serum levels of protein PLXNA1 4e-20 rs1347003 1 GCST90090443 no MR -> candidate analysis
Educational attainment 7e-15 rs1351665 1 GCST90105038 no MR -> candidate analysis
Platelet count 3e-14 rs1106863 2 GCST90002361 MR: beta=-36.3, p=0.443 (cis)
Blood protein levels 1e-11 rs891762 1 GCST006585 no MR -> candidate analysis
Hair color 1e-10 rs61263161 1 GCST007082 no MR -> candidate analysis
Gamma glutamyl transferase levels 6e-10 rs2033421 1 GCST90662899 no MR -> candidate analysis
…and 12 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 182 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
Dworschak-Punetha neurodevelopmental syndrome 0.887 established (curated) no MR -> candidate analysis
neurodevelopmental disorder 0.669 established (curated) no MR -> candidate analysis
skin aging 0.644 common-variant locus no MR -> candidate analysis
complex neurodevelopmental disorder 0.608 established (curated) no MR -> candidate analysis
placental retention 0.58 common-variant locus no MR -> candidate analysis
ovarian dysfunction 0.551 common-variant locus no MR -> candidate analysis
Apnea 0.509 common-variant locus no MR -> candidate analysis
preeclampsia 0.302 common-variant locus no MR -> candidate analysis
Parkinson disease 0.195 established (curated) no MR -> candidate analysis
parkinsonian disorder 0.195 established (curated) no MR -> candidate analysis
vascular parkinsonism 0.195 established (curated) no MR -> candidate analysis
retinal disorder 0.168 common-variant locus no MR -> candidate analysis
chronic intestinal vascular insufficiency 0.132 common-variant locus no MR -> candidate analysis
Paralytic ileus 0.122 common-variant locus no MR -> candidate analysis

Of the 14 rows above, 14 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=0.63, LOEUF=0.486 — LoF-tolerant
GWAS Catalog 31 unique SNPs / 62 rows
ClinVar 1076 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance