CausalSentinel

Protein Dossier — ADAM22 (Disintegrin and metalloproteinase domain-containing protein 22)

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
Schizophrenia -0.25 0.0599 3.05e-05 Wald ratio 1 cis NA
Alcohol intake frequency -0.0598 0.0201 0.00294 Wald ratio 1 cis NA
Clear cell ovarian cancer -0.595 0.227 0.00874 Wald ratio 1 cis NA
Happiness -0.0428 0.0168 0.0109 Wald ratio 1 cis NA
Non-cancer illness code self-reported: retinal detachment 0.382 0.167 0.0221 Wald ratio 1 cis NA
PGC cross-disorder traits -0.164 0.0729 0.0245 Wald ratio 1 cis NA
Femoral neck bone mineral density 0.0876 0.0425 0.0392 Wald ratio 1 cis NA
Neuroticism -0.0339 0.0169 0.0455 Wald ratio 1 cis NA
Diagnoses - main ICD10: K20 Oesophagitis 0.223 0.111 0.0456 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt 0.235 0.121 0.0522 Wald ratio 1 cis NA
Knee and hip osteoarthritis -0.231 0.119 0.0525 Wald ratio 1 cis NA
Body mass index (BMI) -0.026 0.0136 0.0559 Wald ratio 1 cis NA
…and 60 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

37 association rows across 19 traits (25 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
ADAM22/EPHB6 protein level ratio 2e-2411 rs2279542 1 GCST90313168 no MR -> candidate analysis
Circulating ADAM22 levels 8e-762 rs10952901 6 GCST90859681 no MR -> candidate analysis
ADAM22 protein levels 3e-114 rs140448385 8 GCST90468218 no MR -> candidate analysis
Disintegrin and metalloproteinase domain-containing protein 4e-70 rs2279542 4 GCST90247307 no MR -> candidate analysis
Serum levels of protein ADAM22 6e-17 rs2279542 2 GCST90089934 no MR -> candidate analysis
Aspartate aminotransferase to alanine aminotransferase ratio 6e-10 rs73200363 1 GCST90019498 no MR -> candidate analysis
Educational attainment 9e-10 rs1637492 1 GCST90105038 no MR -> candidate analysis
Height 3e-8 rs73202341 3 GCST008904 no MR -> candidate analysis
RBC levels of Phe (uM) 3e-8 rs111428945 1 GCST90267513 no MR -> candidate analysis
Color vision defects (Tritan) 7e-8 rs74349663 1 GCST90301671 no MR -> candidate analysis
TestASV_38 (Ruminococcus) prevalence 1e-6 rs3761806 1 GCST90011713 no MR -> candidate analysis
Metabolite levels 4e-6 rs1201841 1 GCST009391 no MR -> candidate analysis
…and 7 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 424 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
developmental and epileptic encephalopathy, 61 0.8 established (curated) no MR -> candidate analysis
cholelithiasis 0.585 common-variant locus no MR -> candidate analysis
vertebral column disorder 0.4 common-variant locus no MR -> candidate analysis
Abnormality of the immune system 0.4 common-variant locus no MR -> candidate analysis
hereditary disease 0.318 established (curated) no MR -> candidate analysis
Abnormality of the skeletal system 0.305 common-variant locus no MR -> candidate analysis
Respiratory insufficiency 0.302 common-variant locus no MR -> candidate analysis
Subdural hemorrhage 0.299 common-variant locus no MR -> candidate analysis
Intrahepatic cholestasis of pregnancy 0.139 common-variant locus no MR -> candidate analysis

Of the 9 rows above, 9 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=0.00026, LOEUF=0.553 — LoF-tolerant
GWAS Catalog 44 unique SNPs / 88 rows
ClinVar 214 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance