CausalSentinel

Protein Dossier — HSPB1 (Heat shock protein beta-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
Non-cancer illness code self-reported: hypertension -0.0478 0.0129 2.24e-04 Wald ratio 1 cis NA
Body mass index (BMI) -0.0212 0.00724 0.00342 Wald ratio 1 cis NA
Alzheimer’s disease 0.132 0.0486 0.00676 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma 0.137 0.0528 0.00936 Wald ratio 1 cis NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia 0.131 0.051 0.0105 Wald ratio 1 cis NA
Caudate volume -38.9 15.5 0.0122 Wald ratio 1 cis NA
Weight -0.0153 0.00639 0.0165 Wald ratio 1 cis NA
Putamen volume -44.7 19.1 0.0195 Wald ratio 1 cis NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) 0.107 0.0462 0.0212 Wald ratio 1 cis NA
Amyotrophic lateral sclerosis -0.122 0.0542 0.0244 Wald ratio 1 cis NA
Non-cancer illness code self-reported: mania or bipolar disorder or manic depression 0.245 0.113 0.03 Wald ratio 1 cis NA
Invasive mucinous ovarian cancer 0.239 0.121 0.0477 Wald ratio 1 cis NA
…and 68 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

32 association rows across 19 traits (27 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
Circulating HSPB1 levels 7e-1848 rs2868371 1 GCST90859826 no MR -> candidate analysis
Heat shock 27 kDa protein levels 1e-553 rs2868371 2 GCST90012028 no MR -> candidate analysis
Heat shock protein beta-1 levels 7e-553 rs2908203 5 GCST90247943 no MR -> candidate analysis
HSPB1 protein levels 2e-153 rs2908203 7 GCST90453114 no MR -> candidate analysis
A0A6Q8PFK8;HSPB1 protein level (protein group normalized int 1e-26 rs2908203 1 GCST90570781 no MR -> candidate analysis
Serum levels of protein HSPB1 7e-25 rs2908203 1 GCST90086539 no MR -> candidate analysis
ZP3 protein levels 4e-24 rs111362096 2 GCST90471105 no MR -> candidate analysis
CCL24 protein levels 2e-22 rs77586767 2 GCST90468576 no MR -> candidate analysis
Blood protein levels 2e-16 rs2868371 1 GCST006585 no MR -> candidate analysis
Plexin-A1 protein levels (SomaScan ID:11103-24) 3e-15 rs28584236 1 GCST90438260 no MR -> candidate analysis
Circulating CCL24 levels 7e-13 rs111515579 1 GCST90859940 no MR -> candidate analysis
Ventral frontal thickness 5e-9 rs2903813 1 GCST90572712 no MR -> candidate analysis
…and 7 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 630 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
neuronopathy, distal hereditary motor, type 2B 0.957 established (curated) no MR -> candidate analysis
Charcot-Marie-Tooth disease axonal type 2F 0.931 established (curated) no MR -> candidate analysis
Autosomal dominant Charcot-Marie-Tooth disease type 2F 0.847 established (curated) no MR -> candidate analysis
Charcot-Marie-Tooth disease 0.872 established (curated) no MR -> candidate analysis
hereditary disease 0.837 established (curated) no MR -> candidate analysis
distal hereditary motor neuropathy type 2 0.598 established (curated) no MR -> candidate analysis
distal hereditary motor neuropathy 0.559 established (curated) no MR -> candidate analysis
Charcot-Marie-Tooth disease type 4 0.228 established (curated) no MR -> candidate analysis
hereditary peripheral neuropathy 0.195 established (curated) no MR -> candidate analysis

Of the 9 rows above, 9 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 (Heat shock protein beta-1)
gnomAD constraint pLI=7.8e-08, LOEUF=1.64 — LoF-tolerant
GWAS Catalog 75 unique SNPs / 150 rows
ClinVar 471 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance