CausalSentinel

Protein Dossier — DNAJB9 (DnaJ homolog subfamily B member 9)

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
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 2.44 0.229 1.86e-26 Wald ratio 1 trans NA
LDL cholesterol 0.156 0.0211 1.41e-13 Wald ratio 1 trans 1
Diagnoses - main ICD10: K80 Cholelithiasis 0.283 0.0566 5.77e-07 Wald ratio 1 trans NA
Total cholesterol 0.102 0.0208 1.01e-06 Wald ratio 1 trans NA
Diagnoses - main ICD10: R07 Pain in throat and chest 0.176 0.0403 1.28e-05 Wald ratio 1 trans NA
Non-cancer illness code self-reported: high cholesterol 0.0918 0.0265 5.42e-04 Wald ratio 1 trans NA
Diagnoses - main ICD10: R11 Nausea and vomiting 0.347 0.123 0.00482 Wald ratio 1 trans NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.217 0.0825 0.00838 Wald ratio 1 trans NA
HDL cholesterol -0.0538 0.0207 0.00924 Wald ratio 1 trans NA
Forced vital capacity (FVC) -0.0222 0.00881 0.0118 Wald ratio 1 trans NA
Non-cancer illness code self-reported: depression -0.0994 0.049 0.0427 Wald ratio 1 trans NA
Weight -0.0182 0.00949 0.0544 Wald ratio 1 trans NA
…and 61 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

27 association rows across 15 traits (20 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
LAMB1 protein levels 9e-23 rs73195464 3 GCST90469732 no MR -> candidate analysis
NRCAM protein levels 3e-20 rs145468221 2 GCST90470082 no MR -> candidate analysis
Insomnia 8e-13 rs10254670 7 GCST90131901 no MR -> candidate analysis
Exostosis of jaw (PheCode 526.8) 4e-11 rs538989321 1 GCST90480282 no MR -> candidate analysis
Protein quantitative trait loci (liver) 1e-9 rs6971377 3 GCST011427 no MR -> candidate analysis
Body size at age 10 3e-9 rs10953577 1 GCST010989 no MR -> candidate analysis
Educational attainment (years of education) 6e-9 rs78270331 2 GCST006442 no MR -> candidate analysis
Cerebellar grey matter morphology (MOSTest) 6e-9 rs7811819 1 GCST90728589 no MR -> candidate analysis
Hippocampus volume change rate x age interaction (1df) 6e-8 rs2215141 1 GCST90128565 no MR -> candidate analysis
Breast dense area 1e-7 rs138864371 1 GCST90293091 no MR -> candidate analysis
Hippocampus volume change rate x age interaction (2df) 2e-7 rs2215141 1 GCST90128580 no MR -> candidate analysis
Metabolite levels 4e-7 rs13231248 1 GCST009391 no MR -> candidate analysis
…and 3 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 178 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
insomnia 0.271 common-variant locus no MR -> candidate analysis
crush injury 0.236 common-variant locus no MR -> candidate analysis
pulmonary vascular congestion 0.228 common-variant locus no MR -> candidate analysis
ovarian dysfunction 0.228 common-variant locus no MR -> candidate analysis
myopia 0.186 common-variant locus no MR -> candidate analysis
polycythemia 0.168 common-variant locus no MR -> candidate analysis
trauma complication 0.124 common-variant locus no MR -> candidate analysis
exostosis 0.113 common-variant locus no MR -> candidate analysis
type 1 diabetes mellitus 0.088 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.065 common-variant locus no MR -> candidate analysis
coffee consumption 0.059 common-variant locus no MR -> candidate analysis

Of the 11 rows above, 11 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=0.0029, LOEUF=1.01 — LoF-tolerant
GWAS Catalog 30 unique SNPs / 48 rows
ClinVar 67 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance