CausalSentinel

Protein Dossier — ART4 (Ecto-ADP-ribosyltransferase 4)

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 -0.0213 0.00433 8.90e-07 Wald ratio 1 cis NA
Fractured or broken bones in last 5 years 0.0454 0.00998 5.32e-06 Wald ratio 1 cis NA
Height -0.0124 0.00405 0.00216 Wald ratio 1 cis NA
Lumbar spine bone mineral density -0.0362 0.0121 0.00274 Wald ratio 1 cis NA
Fractured bone site(s): Ankle 0.0784 0.0264 0.003 Wald ratio 1 cis NA
Femoral neck bone mineral density -0.0272 0.0104 0.00858 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis -0.0826 0.0343 0.0158 Wald ratio 1 cis NA
Fractured bone site(s): Wrist 0.0545 0.0226 0.016 Wald ratio 1 cis NA
Weight -0.00698 0.00296 0.0182 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis 0.0591 0.0253 0.0197 Wald ratio 1 cis NA
Diagnoses - main ICD10: H25 Senile cataract -0.0943 0.042 0.0248 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.0579 0.0264 0.0282 Wald ratio 1 cis NA
…and 99 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

5 association rows across 5 traits (5 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
Ecto-ADP-ribosyltransferase 4 levels 9e-1651 rs10772808 1 GCST90246589 no MR -> candidate analysis
Ecto-ADP-ribosyltransferase 4 levels (ART4.6576.1.3) 1e-254 rs1001096 1 GCST90241017 no MR -> candidate analysis
Ecto-ADP-ribosyltransferase 4 level in Chronic kidney diseas 7e-63 rs11056202 1 GCST90238347 no MR -> candidate analysis
Protrudin:Cytoplasmic domain, region 1, isoform 6 protein le 4e-39 rs12822851 1 GCST90437421 no MR -> candidate analysis
Hand grip strength 1e-12 rs2287226 1 GCST005830 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 855 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
osteoarthritis, knee 0.63 common-variant locus MR: beta=-0.0273, p=0.332 (cis)
preeclampsia 0.548 common-variant locus no MR -> candidate analysis
total knee arthroplasty 0.53 common-variant locus no MR -> candidate analysis
osteoarthritis, hand 0.421 common-variant locus no MR -> candidate analysis
alcohol drinking 0.368 common-variant locus no MR -> candidate analysis
urolithiasis 0.368 common-variant locus no MR -> candidate analysis
osteoarthritis, hip 0.285 common-variant locus MR: beta=-0.0273, p=0.332 (cis)
polyarticular arthritis 0.217 common-variant locus no MR -> candidate analysis
bone fracture 0.144 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.05 common-variant locus no MR -> candidate analysis
stomach disorder 0.05 common-variant locus no MR -> candidate analysis
endometriosis 0.04 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 10 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=0.0031, LOEUF=0.904 — LoF-tolerant
GWAS Catalog 48 unique SNPs / 96 rows
ClinVar 89 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance