CausalSentinel

Protein Dossier — ADA2 (Adenosine deaminase 2)

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
Weight -0.00895 0.00258 5.25e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] -0.0801 0.0264 0.0024 Wald ratio 1 cis NA
Rheumatoid arthritis 0.0663 0.0219 0.00249 Wald ratio 1 cis NA
Bulimia nervosa 0.0262 0.0091 0.00404 Wald ratio 1 cis NA
Non-cancer illness code self-reported: muscle or soft tissue injuries -0.0941 0.038 0.0132 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate -0.0786 0.0329 0.0171 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes -0.0121 0.00511 0.0176 Wald ratio 1 cis NA
Neo-openness to experience -0.219 0.0948 0.0207 Wald ratio 1 cis NA
Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level 0.145 0.0636 0.0224 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb -0.0519 0.0234 0.0267 Wald ratio 1 cis NA
HDL cholesterol 0.0138 0.00637 0.0307 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma 0.0492 0.0232 0.0339 Wald ratio 1 cis NA
…and 108 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

52 association rows across 25 traits (48 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
Adenosine deaminase CECR1 levels 3e-985 rs2231495 5 GCST90246979 no MR -> candidate analysis
Adenosine deaminase CECR1 levels (CECR1.6077.63.3) 1e-370 rs2231495 2 GCST90240191 no MR -> candidate analysis
Blood protein levels 9e-370 rs2231495 2 GCST006585 no MR -> candidate analysis
ADA2/VCAM1 protein level ratio 2e-286 rs9606655 1 GCST90313167 no MR -> candidate analysis
IL17RA protein levels 3e-286 rs5748923 14 GCST90469562 no MR -> candidate analysis
ADA2 protein levels 1e-265 rs737963 5 GCST90468215 no MR -> candidate analysis
Protein S100-A11 levels 9e-243 rs2231495 2 GCST90249401 no MR -> candidate analysis
Interleukin-17 receptor A levels 8e-47 rs5992639 3 GCST90248041 no MR -> candidate analysis
Adenosine deaminase CECR1 level in Chronic kidney disease wi 1e-44 rs2231495 1 GCST90238152 no MR -> candidate analysis
Arylsulfatase B levels 3e-35 rs2231495 1 GCST90246585 no MR -> candidate analysis
Serum levels of protein PTHLH 5e-27 rs2231495 1 GCST90088151 no MR -> candidate analysis
Parathyroid hormone-related protein levels 3e-25 rs2231495 1 GCST90249173 no MR -> candidate analysis
…and 13 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 498 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
deficiency of adenosine deaminase 2 0.916 established (curated) no MR -> candidate analysis
Sneddon syndrome 0.84 established (curated) no MR -> candidate analysis
polyarteritis nodosa, childhoood-onset 0.945 established (curated) no MR -> candidate analysis
Diamond-Blackfan anemia 0.608 established (curated) no MR -> candidate analysis
Blackfan-Diamond anemia 0.608 established (curated) no MR -> candidate analysis
autoinflammatory syndrome 0.83 established (curated) no MR -> candidate analysis
Behcet disease 0.779 established (curated) no MR -> candidate analysis
Splenomegaly 0.559 established (curated) no MR -> candidate analysis
immunodeficiency disease 0.547 established (curated) no MR -> candidate analysis
polyarteritis nodosa 0.438 established (curated) no MR -> candidate analysis
preeclampsia 0.349 common-variant locus no MR -> candidate analysis
bone Paget disease 0.319 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 12 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=7e-07, LOEUF=0.894 — LoF-tolerant
GWAS Catalog 104 unique SNPs / 231 rows
ClinVar 705 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance