CausalSentinel

Protein Dossier — PSMB1 (Proteasome subunit beta type-1)

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
Age at menarche -0.0388 0.0141 0.0059 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0716 0.0282 0.011 Wald ratio 1 cis NA
Weight -0.0123 0.00524 0.0188 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes -0.0242 0.0105 0.0212 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt 0.131 0.058 0.0239 Wald ratio 1 cis NA
Years of schooling -0.0218 0.00971 0.0244 Wald ratio 1 cis NA
Body mass index (BMI) -0.0131 0.00594 0.0278 Wald ratio 1 cis NA
Alzheimer’s disease -0.0854 0.0403 0.034 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine -0.0957 0.0461 0.0378 Wald ratio 1 cis NA
Myocardial infarction 0.0511 0.0253 0.0435 Wald ratio 1 cis NA
Gallbladder cancer -1.6 0.796 0.0443 Wald ratio 1 cis NA
Mean cell haemoglobin concentration 0.0167 0.0085 0.0487 Wald ratio 1 cis NA
…and 101 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

11 association rows across 10 traits (10 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
Serum levels of protein PSMB1 2e-101 rs6930789 1 GCST90087098 no MR -> candidate analysis
Blood protein levels 8e-67 rs756519 1 GCST006585 no MR -> candidate analysis
Adolescent idiopathic scoliosis 1e-31 rs760500 1 GCST006287 no MR -> candidate analysis
Height 1e-27 rs11755081 2 GCST90245848 MR: beta=-0.0117, p=0.11 (cis)
Hematological traits (multi-trait analysis) 2e-13 rs9460014 1 GCST90838669 no MR -> candidate analysis
Red blood cell count 1e-11 rs9460014 1 GCST90002363 no MR -> candidate analysis
Platelet count 3e-11 rs9460014 1 GCST90002357 no MR -> candidate analysis
Total bilirubin levels 6e-9 rs11755081 1 GCST90662900 no MR -> candidate analysis
Dorsolateral prefrontal area 2e-8 rs6915605 1 GCST90572714 no MR -> candidate analysis
Memory decline in normal cognition 5e-6 rs7753099 1 GCST90448447 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 273 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
neurodevelopmental disorder with microcephaly, hypotonia, and absent language 0.596 established (curated) no MR -> candidate analysis
alcohol drinking 0.339 common-variant locus no MR -> candidate analysis

Of the 2 rows above, 2 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 0 known modulators (Proteasome component C5)
gnomAD constraint pLI=0.97, LOEUF=0.518 — LoF-INTOLERANT
GWAS Catalog 28 unique SNPs / 42 rows
ClinVar 134 records; 10 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance