CausalSentinel

Protein Dossier — HSP90B1 (Endoplasmin)

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
Heel bone mineral density (BMD) T-score automated -0.0114 0.00308 2.26e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: sleep apnoea -0.161 0.0505 0.00149 Wald ratio 1 cis NA
Sleep duration -0.00581 0.00186 0.00179 Wald ratio 1 cis NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) 0.048 0.0161 0.00284 Wald ratio 1 cis NA
Crohn’s disease -0.0338 0.0124 0.00618 Wald ratio 1 cis NA
Chronic kidney disease 0.0392 0.0146 0.0072 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis -0.0267 0.0101 0.00786 Wald ratio 1 cis NA
Sodium in urine -0.00611 0.00234 0.00906 Wald ratio 1 cis NA
Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis 0.0812 0.0322 0.0115 Wald ratio 1 cis NA
Inflammatory bowel disease -0.025 0.0102 0.0142 Wald ratio 1 cis NA
Knee osteoarthritis 0.0564 0.0271 0.0374 Wald ratio 1 cis NA
Diagnoses - main ICD10: G47 Sleep disorders -0.0656 0.0332 0.048 Wald ratio 1 cis NA
…and 99 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

30 association rows across 22 traits (29 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
Endoplasmin levels (HSP90B1.6393.63.3) 4e-795 rs1165693 1 GCST90241048 no MR -> candidate analysis
Endoplasmin levels 2e-250 rs1177457 2 GCST90426673 no MR -> candidate analysis
Potassium voltage-gated channel subfamily A member 10 levels 7e-240 rs1177457 2 GCST90422054 no MR -> candidate analysis
HSP90B1 protein levels 7e-166 rs1177457 4 GCST90453183 no MR -> candidate analysis
Serum levels of protein HSP90B1 7e-156 rs2583273 1 GCST90089394 no MR -> candidate analysis
Endoplasmin level in Chronic kidney disease with hypertensio 1e-106 rs1165692 1 GCST90238248 no MR -> candidate analysis
Serum levels of protein HNRNPM 6e-103 rs1165683 1 GCST90087223 no MR -> candidate analysis
Height 8e-47 rs4964375 2 GCST90245848 MR: beta=0.00328, p=0.261 (cis)
Paralemmin-1 protein levels (SomaScan ID:6393-63) 1e-37 rs1177457 1 GCST90443384 no MR -> candidate analysis
Heterogeneous nuclear ribonucleoprotein M levels 9e-24 rs1165695 1 GCST90247916 no MR -> candidate analysis
Leucine-rich repeat, immunoglobulin-like domain and transmem 2e-23 rs3830654 1 GCST90248331 no MR -> candidate analysis
CRELD2 protein levels 8e-21 rs2583273 1 GCST90468859 no MR -> candidate analysis
…and 10 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 449 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
Dysmetria 0.401 common-variant locus no MR -> candidate analysis
venous thromboembolism 0.393 common-variant locus no MR -> candidate analysis
diverticular disease 0.378 common-variant locus MR: beta=-0.0387, p=0.0982 (cis)
atrial septal defect 0.309 common-variant locus no MR -> candidate analysis

Of the 4 rows above, 3 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 (Endoplasmin)
gnomAD constraint pLI=1, LOEUF=0.371 — LoF-INTOLERANT
GWAS Catalog 66 unique SNPs / 129 rows
ClinVar 134 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance