CausalSentinel

Protein Dossier — PSMD5 (26S proteasome non-ATPase regulatory subunit 5)

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
Diagnoses - main ICD10: H25 Senile cataract 0.281 0.097 0.00381 Wald ratio 1 trans NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] 0.189 0.0668 0.00458 Wald ratio 1 trans NA
Diagnoses - main ICD10: R55 Syncope and collapse 0.214 0.0965 0.0263 Wald ratio 1 trans NA
Weight 0.0215 0.00984 0.029 Wald ratio 1 trans NA
Potassium in urine 0.0236 0.0113 0.0369 Wald ratio 1 trans NA
Forced vital capacity (FVC) -0.018 0.00915 0.0497 Wald ratio 1 trans NA
Body mass index (BMI) 0.0218 0.0111 0.05 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) -0.0188 0.00965 0.0511 Wald ratio 1 trans NA
Non-cancer illness code self-reported: migraine 0.112 0.0578 0.0538 Wald ratio 1 trans NA
Diagnoses - main ICD10: R35 Polyuria 0.267 0.14 0.0562 Wald ratio 1 trans NA
Diagnoses - main ICD10: B37 Candidiasis 0.617 0.324 0.0566 Wald ratio 1 trans NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal 0.153 0.0814 0.0593 Wald ratio 1 trans NA
…and 52 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

12 association rows across 10 traits (11 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
Height 5e-86 rs12343516 1 GCST90245848 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 2e-25 rs10818476 1 GCST90838671 no MR -> candidate analysis
heart rate (HR, minimum, inv-normal transformed) 7e-18 rs12343516 2 GCST90476341 no MR -> candidate analysis
MEGF9 protein levels 8e-16 rs143794270 1 GCST90469884 no MR -> candidate analysis
Platelet count 9e-15 rs1060817 1 GCST90002361 MR: beta=-13.2, p=0.489 (trans)
heart rate (HR, mean, inv-normal transformed) 1e-14 rs12343516 1 GCST90480666 no MR -> candidate analysis
Systolic blood pressure 6e-10 rs10760117 1 GCST006259 MR: beta=0.0132, p=0.245 (trans)
Hip circumference adjusted for BMI 2e-9 rs62581708 2 GCST90020028 no MR -> candidate analysis
Height (baseline) 1e-8 rs150211503 1 GCST90565843 no MR -> candidate analysis
Autoimmune traits 1e-7 rs13299616 1 GCST007071 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 56 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
Crohn disease 0.476 common-variant locus no MR -> candidate analysis
thyroid gland disorder 0.459 common-variant locus no MR -> candidate analysis
alcohol drinking 0.414 common-variant locus no MR -> candidate analysis
atopic eczema 0.226 common-variant locus no MR -> candidate analysis
benign prostatic hyperplasia 0.186 common-variant locus no MR -> candidate analysis
rheumatoid arthritis 0.055 common-variant locus no MR -> candidate analysis
complex regional pain syndrome 0.044 common-variant locus no MR -> candidate analysis
placental abruption 0.042 common-variant locus no MR -> candidate analysis
autoimmune disease 0.041 common-variant locus no MR -> candidate analysis
urethral syndrome 0.041 common-variant locus no MR -> candidate analysis
neutropenia 0.04 common-variant locus no MR -> candidate analysis
systemic lupus erythematosus 0.036 common-variant locus no MR -> candidate analysis
bipolar disorder 0.035 common-variant locus no MR -> candidate analysis
Graves disease 0.034 common-variant locus no MR -> candidate analysis
ACPA-positive rheumatoid arthritis 0.032 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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 (26S proteasome non-ATPase regulatory subunit 5)
gnomAD constraint pLI=4.7e-11, LOEUF=0.999 — LoF-tolerant
GWAS Catalog 85 unique SNPs / 170 rows
ClinVar 109 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance