CausalSentinel

Protein Dossier — ADAM19 (Disintegrin and metalloproteinase domain-containing protein 19)

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) 0.0682 0.00892 2.10e-14 Wald ratio 1 cis NA
Height 0.0488 0.0126 1.08e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma -0.126 0.0328 1.21e-04 Wald ratio 1 cis NA
Hippocampus volume 63.7 20 0.00148 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0245 0.00846 0.00371 Wald ratio 1 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain -0.157 0.0585 0.00714 Wald ratio 1 cis NA
Intracranial volume 1.99e+04 8.17e+03 0.015 Wald ratio 1 cis NA
Neo-conscientiousness -0.748 0.312 0.0166 Wald ratio 1 cis NA
Subjective well being 0.0285 0.0122 0.0196 Wald ratio 1 cis NA
Invasive mucinous ovarian cancer 0.396 0.173 0.0218 Wald ratio 1 cis NA
HDL cholesterol -0.0419 0.0199 0.0355 Wald ratio 1 cis NA
Paget’s disease -0.524 0.249 0.0356 Wald ratio 1 cis NA
…and 109 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

91 association rows across 69 traits (81 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
Lung function (FEV1/FVC) 3e-91 rs11134789 6 GCST007080 no MR -> candidate analysis
FEV1/FVC ratio 7e-75 rs4331881 1 GCST90705072 no MR -> candidate analysis
FEV1 FVC ratio Z score (UKB data field 20258) 1e-69 rs112325689 1 GCST90468165 no MR -> candidate analysis
HAVCR1 protein levels 4e-58 rs11466764 1 GCST90469431 no MR -> candidate analysis
Chronic obstructive pulmonary disease liability (machine lea 2e-50 rs1990950 1 GCST90244098 no MR -> candidate analysis
Serum levels of protein ADAM19 1e-33 rs7728609 1 GCST90090399 no MR -> candidate analysis
Forced expiratory volume in 1 second (FEV1) 6e-27 rs13361953 1 GCST90705070 no MR -> candidate analysis
Peak expiratory flow 5e-25 rs11134789 3 GCST007430 no MR -> candidate analysis
FEV1 6e-25 rs11134789 3 GCST007432 MR: beta=0.0682, p=2.10e-14 (cis)
Hematological traits (multi-trait analysis) 3e-23 rs34197759 1 GCST90838669 no MR -> candidate analysis
Blood protein levels 1e-21 rs7728609 1 GCST006585 no MR -> candidate analysis
Forced expiratory volume in 1 second FEV1 Z score (UKB data 3e-21 rs11134789 1 GCST90468166 no MR -> candidate analysis
…and 57 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 1018 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
coronary artery disorder 0.695 common-variant locus no MR -> candidate analysis
asthma 0.661 common-variant locus MR: beta=-0.126, p=1.21e-04 (cis)
chronic obstructive pulmonary disease 0.661 common-variant locus no MR -> candidate analysis
coronary atherosclerosis 0.534 common-variant locus no MR -> candidate analysis
cholelithiasis 0.403 common-variant locus MR: beta=-0.177, p=0.0409 (cis)
non-autoimmune hemolytic anemia 0.393 common-variant locus no MR -> candidate analysis
gastroesophageal reflux disease 0.351 common-variant locus no MR -> candidate analysis
lower respiratory tract disorder 0.239 common-variant locus no MR -> candidate analysis
Chronic Obstructive Asthma 0.226 common-variant locus no MR -> candidate analysis

Of the 9 rows above, 7 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=8.8e-11, LOEUF=0.696 — LoF-tolerant
GWAS Catalog 89 unique SNPs / 151 rows
ClinVar 181 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance