Protein Dossier — GZMB (Granzyme B)
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: M54 Dorsalgia |
0.109 |
0.03 |
2.70e-04 |
Wald ratio |
1 |
cis |
NA |
| Lung adenocarcinoma |
-0.132 |
0.0441 |
0.00284 |
Wald ratio |
1 |
cis |
NA |
| Neo-agreeableness |
-0.307 |
0.106 |
0.00388 |
Wald ratio |
1 |
cis |
NA |
| Creatinine (enzymatic) in urine |
-0.0107 |
0.00413 |
0.00956 |
Wald ratio |
1 |
cis |
NA |
| Forearm bone mineral density |
0.0705 |
0.0273 |
0.00994 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: N40 Hyperplasia of prostate |
-0.126 |
0.051 |
0.0137 |
Wald ratio |
1 |
cis |
NA |
| Lung cancer |
-0.0698 |
0.0301 |
0.0203 |
Wald ratio |
1 |
cis |
NA |
| Cough on most days |
-0.0538 |
0.0233 |
0.0211 |
Wald ratio |
1 |
cis |
NA |
| Alcohol intake frequency |
-0.0131 |
0.00637 |
0.0396 |
Wald ratio |
1 |
cis |
NA |
| Birth weight |
-0.0132 |
0.00643 |
0.0407 |
Wald ratio |
1 |
cis |
NA |
| Mean cell haemoglobin |
0.0371 |
0.0185 |
0.0455 |
Wald ratio |
1 |
cis |
NA |
| Potassium in urine |
-0.00867 |
0.00438 |
0.0475 |
Wald ratio |
1 |
cis |
NA |
| …and 87 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4133_54_2 |
Granzyme B |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
16 association rows across 11 traits (16 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 GZMB levels (id: OID00743_OID20604) |
2e-571 |
rs8192917 |
1 |
GCST90860084 |
no MR -> candidate analysis |
| Circulating GZMB levels (id: OID00840_OID20604) |
3e-544 |
rs8192917 |
1 |
GCST90860165 |
no MR -> candidate analysis |
| GZMA/GZMB protein level ratio |
3e-489 |
rs8192917 |
1 |
GCST90315007 |
no MR -> candidate analysis |
| Granzyme B levels (GZMB.4133.54.2) |
6e-352 |
rs8192917 |
2 |
GCST90241324 |
no MR -> candidate analysis |
| Serum levels of protein GZMB |
5e-131 |
rs8192917 |
1 |
GCST90087736 |
no MR -> candidate analysis |
| Blood protein levels |
3e-83 |
rs11539752 |
2 |
GCST006585 |
no MR -> candidate analysis |
| GZMB protein levels |
1e-39 |
rs59268439 |
3 |
GCST90469424 |
no MR -> candidate analysis |
| Granzyme B (analyte X14041.13) levels |
1e-22 |
rs8192917 |
1 |
GCST90422424 |
no MR -> candidate analysis |
| Vitiligo |
9e-16 |
rs8192917 |
2 |
GCST004785 |
no MR -> candidate analysis |
| Hairy/enhancer-of-split related with YRPW motif protein 1 pr |
1e-9 |
rs8192917 |
1 |
GCST90437219 |
no MR -> candidate analysis |
| Nuclear receptor coactivator 7 protein levels (SomaScan ID:4 |
3e-8 |
rs2236338 |
1 |
GCST90443089 |
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 961 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 |
| vitiligo |
0.55 |
— |
common-variant locus |
no MR -> candidate analysis |
| respiratory failure |
0.448 |
— |
common-variant locus |
no MR -> candidate analysis |
| bone remodeling disease |
0.353 |
— |
common-variant locus |
no MR -> candidate analysis |
| respiratory tract neoplasm |
0.314 |
— |
common-variant locus |
no MR -> candidate analysis |
| alcohol drinking |
0.306 |
— |
common-variant locus |
no MR -> candidate analysis |
| diabetes mellitus |
0.158 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 6 rows above, 6 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 (Granzyme B) |
| gnomAD constraint |
pLI=1e-10, LOEUF=1.54 — LoF-tolerant |
| GWAS Catalog |
35 unique SNPs / 70 rows |
| ClinVar |
78 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 961 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘GZMB’ and resolved to ‘Granzyme B’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 78 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 11 of 11 traits by best p-value, aggregated from 16 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/P10144 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000100453/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2316/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/GZMB — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/GZMB — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=GZMB%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/GZMB — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:56:50 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none