CausalSentinel

Protein Dossier — ADAM23 (Disintegrin and metalloproteinase domain-containing protein 23)

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
Diagnoses - main ICD10: K80 Cholelithiasis -0.129 0.0476 0.00675 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vitiligo 0.558 0.22 0.0112 Wald ratio 1 cis NA
Knee osteoarthritis 0.168 0.0695 0.0157 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine -0.113 0.0473 0.0172 Wald ratio 1 cis NA
Birth weight 0.0211 0.00903 0.0196 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.0949 0.0415 0.0223 Wald ratio 1 cis NA
HbA1C -0.0187 0.00879 0.033 Wald ratio 1 cis NA
Alzheimer’s disease -0.0773 0.0393 0.0494 Wald ratio 1 cis NA
Eczema -0.0816 0.0421 0.0528 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia 0.065 0.0344 0.0584 Wald ratio 1 cis NA
Non-cancer illness code self-reported: anxiety or panic attacks 0.0876 0.0474 0.0645 Wald ratio 1 cis NA
Height 0.0141 0.00764 0.0645 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

56 association rows across 26 traits (51 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 ADAM23 levels 7e-1768 rs1448903 8 GCST90859683 no MR -> candidate analysis
ADAM23/BSG protein level ratio 8e-1698 rs1448903 1 GCST90313169 no MR -> candidate analysis
ADAM23 protein levels 4e-286 rs74668856 8 GCST90468219 no MR -> candidate analysis
Disintegrin and metalloproteinase domain-containing protein 6e-174 rs1207146 7 GCST90247308 no MR -> candidate analysis
Disintegrin and metalloproteinase domain-containing protein 3e-64 rs1921673 4 GCST90240922 no MR -> candidate analysis
Serum levels of protein ADAM23 8e-63 rs1448903 3 GCST90089632 no MR -> candidate analysis
Blood protein levels 2e-40 rs1448903 1 GCST006585 no MR -> candidate analysis
Childhood body mass index 9e-23 rs143223375 2 GCST90301649 no MR -> candidate analysis
ICD10 J35: Chronic diseases of tonsils and adenoids 1e-20 rs189411872 1 GCST90269775 no MR -> candidate analysis
Neurological blood protein biomarker levels 3e-17 rs1448903 2 GCST008478 no MR -> candidate analysis
Pharyngeal disease 3e-15 rs189411872 1 GCST90269785 no MR -> candidate analysis
Chronic diseases of tonsils or adenoids (MTAG) 1e-13 rs189411872 1 GCST90269792 no MR -> candidate analysis
…and 14 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 917 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
tonsillitis 0.551 common-variant locus no MR -> candidate analysis
alcohol drinking 0.458 common-variant locus no MR -> candidate analysis
disorder of pharynx 0.441 common-variant locus no MR -> candidate analysis
lymphatic system disorder 0.43 common-variant locus no MR -> candidate analysis
upper respiratory tract disorder 0.43 common-variant locus no MR -> candidate analysis
cirrhosis of liver 0.425 common-variant locus no MR -> candidate analysis
biliary tract disorder 0.418 common-variant locus no MR -> candidate analysis
ovarian dysfunction 0.394 common-variant locus no MR -> candidate analysis
retinal edema 0.36 common-variant locus no MR -> candidate analysis
sialadenitis 0.35 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.35 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.244 common-variant locus no MR -> candidate analysis
obesity disorder 0.182 common-variant locus no MR -> candidate analysis

Of the 13 rows above, 13 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=1, LOEUF=0.368 — LoF-INTOLERANT
GWAS Catalog 60 unique SNPs / 120 rows
ClinVar 147 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance