CausalSentinel

Protein Dossier — HBZ (Hemoglobin subunit zeta)

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 0.0112 0.00367 0.00228 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.0324 0.0107 0.00242 Wald ratio 1 cis NA
Cancer code self-reported: malignant melanoma -0.107 0.0359 0.00288 Wald ratio 1 cis NA
Femoral neck bone mineral density 0.0279 0.00979 0.0043 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bone disorder 0.141 0.0528 0.00758 Wald ratio 1 cis NA
Systolic blood pressure automated reading -0.00745 0.00291 0.0105 Wald ratio 1 cis NA
Pulse rate -0.0116 0.00503 0.0206 Wald ratio 1 cis NA
Forearm bone mineral density 0.0424 0.0187 0.0235 Wald ratio 1 cis NA
Neuroticism -0.0102 0.00452 0.0244 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine -0.046 0.0209 0.0281 Wald ratio 1 cis NA
Diagnoses - main ICD10: B37 Candidiasis 0.235 0.109 0.0304 Wald ratio 1 cis NA
Clear cell ovarian cancer 0.106 0.0502 0.0346 Wald ratio 1 cis NA
…and 74 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

56 association rows across 33 traits (53 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
Hemoglobin subunit zeta levels 1e-685 rs2461286 2 GCST90247854 no MR -> candidate analysis
Hemoglobin subunit zeta levels (HBZ.6919.3.3) 1e-389 rs2461286 2 GCST90241383 no MR -> candidate analysis
Mean corpuscular hemoglobin 7e-162 rs11864973 9 GCST90662875 no MR -> candidate analysis
Mean corpuscular volume 9e-134 rs11864973 7 GCST90662877 no MR -> candidate analysis
Mean corpuscular haemoglobin (UKB data field 30050) 1e-129 rs113613943 2 GCST90468084 no MR -> candidate analysis
HBZ protein levels 1e-96 rs544061540 1 GCST90469435 no MR -> candidate analysis
Mean corpuscular volume (UKB data field 30040) 4e-70 rs11864973 1 GCST90468086 no MR -> candidate analysis
AHSP/CA2 protein level ratio 9e-65 rs7202152 1 GCST90313215 no MR -> candidate analysis
AHSP/BLVRB protein level ratio 2e-60 rs7202152 1 GCST90313214 no MR -> candidate analysis
AHSP/HMBS protein level ratio 3e-50 rs7202152 1 GCST90313217 no MR -> candidate analysis
Red blood cell count 1e-45 rs11864973 4 GCST90662878 no MR -> candidate analysis
Mean corpuscular hemoglobin concentration 7e-30 rs11864973 3 GCST005992 no MR -> candidate analysis
…and 21 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 187 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
anemia (phenotype) 0.247 common-variant locus no MR -> candidate analysis
Iron deficiency anemia 0.251 common-variant locus no MR -> candidate analysis
inherited hemoglobinopathy 0.17 common-variant locus no MR -> candidate analysis
alcohol drinking 0.081 common-variant locus no MR -> candidate analysis
stroke disorder 0.081 common-variant locus no MR -> candidate analysis

Of the 5 rows above, 5 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 (Hemoglobin subunit zeta)
gnomAD constraint pLI=0.42, LOEUF=1.09 — LoF-tolerant
GWAS Catalog 174 unique SNPs / 419 rows
ClinVar 85 records; 14 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance