Protein Dossier — KLKB1 (Plasma kallikrein)
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 |
| Crohn’s disease |
0.971 |
0.102 |
1.74e-21 |
Wald ratio |
1 |
trans |
NA |
| Inflammatory bowel disease |
0.653 |
0.0845 |
1.03e-14 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: hypopituitarism |
0.000383 |
0.000128 |
0.00285 |
Inverse variance weighted |
2 |
trans |
NA |
| Non-cancer illness code self-reported: hypopituitarism |
0.000383 |
0.000128 |
0.00285 |
Inverse variance weighted |
2 |
trans |
NA |
| Ulcerative colitis |
0.319 |
0.107 |
0.0029 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt |
0.0017 |
0.000623 |
0.00638 |
Inverse variance weighted |
2 |
trans |
NA |
| Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt |
0.0017 |
0.000623 |
0.00638 |
Inverse variance weighted |
2 |
trans |
NA |
| Paget’s disease |
0.435 |
0.164 |
0.00807 |
Inverse variance weighted |
2 |
trans |
NA |
| Paget’s disease |
0.435 |
0.164 |
0.00807 |
Inverse variance weighted |
2 |
trans |
NA |
| Thalamus volume |
-37.9 |
17.3 |
0.0284 |
Inverse variance weighted |
2 |
trans |
NA |
| Thalamus volume |
-37.9 |
17.3 |
0.0284 |
Inverse variance weighted |
2 |
trans |
NA |
| Eczema |
0.102 |
0.047 |
0.0297 |
Inverse variance weighted |
2 |
trans |
NA |
| …and 180 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4152_58_2 |
Prekallikrein |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
307 association rows across 258 traits (300 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 BCL2L11 levels |
4e-480 |
rs4253281 |
3 |
GCST90860511 |
no MR -> candidate analysis |
| Circulating BMP6 levels |
6e-447 |
rs4253252 |
1 |
GCST90859741 |
no MR -> candidate analysis |
| Plasma kallikrein levels |
2e-426 |
rs71640035 |
6 |
GCST90249010 |
no MR -> candidate analysis |
| Kininostatin levels |
3e-404 |
rs3733402 |
1 |
GCST90248200 |
no MR -> candidate analysis |
| KLKB1 protein levels |
3e-291 |
rs4253327 |
5 |
GCST90469708 |
no MR -> candidate analysis |
| Circulating VEGFD levels (id: OID00468_OID20662) |
2e-244 |
rs12331618 |
1 |
GCST90859829 |
no MR -> candidate analysis |
| CD84/ITGA6 protein level ratio |
3e-237 |
rs4253252 |
1 |
GCST90313915 |
no MR -> candidate analysis |
| APOL1 protein levels |
8e-229 |
rs4253281 |
1 |
GCST90468341 |
no MR -> candidate analysis |
| NPY protein levels |
6e-201 |
rs4861708 |
1 |
GCST90470081 |
no MR -> candidate analysis |
| Serum levels of protein KLKB1 |
1e-191 |
rs2304595 |
1 |
GCST90088608 |
no MR -> candidate analysis |
| LGMN/SPINT2 protein level ratio |
3e-172 |
rs4253252 |
1 |
GCST90315324 |
no MR -> candidate analysis |
| Circulating ITGA6 levels |
1e-165 |
rs4253238 |
1 |
GCST90860190 |
no MR -> candidate analysis |
| …and 246 more traits (see JSON) |
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4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 550 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 |
| inherited prekallikrein deficiency |
0.892 |
— |
established (curated) |
no MR -> candidate analysis |
| prekallikrein deficiency |
0.825 |
— |
established (curated) |
no MR -> candidate analysis |
| Congenital prekallikrein deficiency |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| venous thromboembolism |
0.823 |
— |
common-variant locus |
no MR -> candidate analysis |
| blood coagulation disease |
0.655 |
— |
established (curated) |
no MR -> candidate analysis |
| serum lipopolysaccharide activity |
0.684 |
— |
common-variant locus |
no MR -> candidate analysis |
| heart disorder |
0.614 |
— |
common-variant locus |
no MR -> candidate analysis |
| cardiovascular disorder |
0.588 |
— |
common-variant locus |
no MR -> candidate analysis |
| coronary artery calcification |
0.579 |
— |
common-variant locus |
no MR -> candidate analysis |
| pulmonary embolism |
0.503 |
— |
common-variant locus |
MR: beta=0.0017, p=0.00638 (trans) |
| drug allergy |
0.416 |
— |
common-variant locus |
no MR -> candidate analysis |
| Pulmonary Infarction |
0.343 |
— |
common-variant locus |
no MR -> candidate analysis |
| deep vein thrombosis |
0.325 |
— |
common-variant locus |
no MR -> candidate analysis |
| Thromboembolism |
0.317 |
— |
common-variant locus |
no MR -> candidate analysis |
| Thrombocytopenia |
0.182 |
— |
established (curated) |
no MR -> candidate analysis |
Of the 15 rows above, 14 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 |
6 known modulators (Plasma kallikrein) |
| gnomAD constraint |
pLI=5.6e-16, LOEUF=0.98 — LoF-tolerant |
| GWAS Catalog |
127 unique SNPs / 326 rows |
| ClinVar |
383 records; 7 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 550 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 ‘KLKB1’ and resolved to ‘Plasma kallikrein’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 383 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 20 of 258 traits by best p-value, aggregated from 307 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/P03952 — 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/ENSG00000164344/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2000/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/KLKB1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/KLKB1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=KLKB1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/KLKB1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:25:47 · 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