CausalSentinel

Protein Dossier — CACNA2D3 (Voltage-dependent calcium channel subunit alpha-2/delta-3)

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 expiratory volume in 1-second (FEV1) 0.0305 0.00796 1.24e-04 Inverse variance weighted 2 cis NA
Forced expiratory volume in 1-second (FEV1) 0.0305 0.00796 1.24e-04 Inverse variance weighted 2 trans NA
Forced vital capacity (FVC) 0.0252 0.00754 8.37e-04 Inverse variance weighted 2 cis NA
Forced vital capacity (FVC) 0.0252 0.00754 8.37e-04 Inverse variance weighted 2 trans NA
Non-cancer illness code self-reported: osteoporosis 0.175 0.0622 0.00479 Inverse variance weighted 2 cis NA
Non-cancer illness code self-reported: osteoporosis 0.175 0.0622 0.00479 Inverse variance weighted 2 trans NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt 0.226 0.082 0.00579 Inverse variance weighted 2 cis NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt 0.226 0.082 0.00579 Inverse variance weighted 2 trans NA
Non-cancer illness code self-reported: hypertension 0.0406 0.0151 0.00703 Inverse variance weighted 2 cis NA
Non-cancer illness code self-reported: hypertension 0.0406 0.0151 0.00703 Inverse variance weighted 2 trans NA
Fasting glucose -0.0301 0.0117 0.0102 Inverse variance weighted 2 cis NA
Fasting glucose -0.0301 0.0117 0.0102 Inverse variance weighted 2 trans NA
…and 186 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

179 association rows across 123 traits (112 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
Height 1e-68 rs358498 8 GCST90245848 MR: beta=0.0502, p=0.386 (cis)
Voltage-dependent calcium channel subunit alpha-2/delta-3 le 7e-45 rs9878608 3 GCST90250154 no MR -> candidate analysis
Lung function (FEV1/FVC) 1e-31 rs17759204 4 GCST007080 no MR -> candidate analysis
FEV1/FVC ratio 4e-29 rs11708743 1 GCST90705072 no MR -> candidate analysis
Leucine-rich repeat and transmembrane domain-containing prot 8e-29 rs1878110 1 GCST90427784 no MR -> candidate analysis
FEV1 FVC ratio Z score (UKB data field 20258) 5e-26 rs17759204 1 GCST90468165 no MR -> candidate analysis
Chronic obstructive pulmonary disease liability (machine lea 2e-25 rs17759204 1 GCST90244098 no MR -> candidate analysis
Facial morphology (segment 2) 3e-24 rs17054293 1 GCST90007245 no MR -> candidate analysis
IL17RB protein levels 2e-22 rs116550666 6 GCST90469563 no MR -> candidate analysis
Type 2 diabetes 5e-22 rs4955988 9 GCST90134620 MR: beta=-0.0486, p=0.258 (cis)
Total PHF-tau (SNP x SNP interaction) 2e-20 rs17053724 x rs11018364 4 GCST010340 no MR -> candidate analysis
Bone mineral density mean 1e-18 rs149885450 3 GCST90321120 no MR -> candidate analysis
…and 111 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 352 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
mathematical ability 0.707 common-variant locus no MR -> candidate analysis
chronic obstructive pulmonary disease 0.077 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.601 common-variant locus no MR -> candidate analysis
placental abruption 0.576 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.563 common-variant locus no MR -> candidate analysis
substance abuse 0.563 common-variant locus no MR -> candidate analysis

Of the 6 rows above, 6 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 9 known modulators (Voltage-gated calcium channel)
gnomAD constraint pLI=1, LOEUF=0.463 — LoF-INTOLERANT
GWAS Catalog 118 unique SNPs / 294 rows
ClinVar 308 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance