Protein Dossier — KLK6 (Kallikrein-6)
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: N40 Hyperplasia of prostate |
0.276 |
0.0659 |
2.75e-05 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis |
0.268 |
0.0939 |
0.0044 |
Wald ratio |
1 |
cis |
NA |
| Body mass index (BMI) |
0.0225 |
0.0083 |
0.00662 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: G47 Sleep disorders |
0.234 |
0.0864 |
0.00664 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions |
0.259 |
0.0959 |
0.00695 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: asthma |
0.0525 |
0.0221 |
0.0173 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal |
-0.202 |
0.0865 |
0.0198 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0163 |
0.00719 |
0.0231 |
Wald ratio |
1 |
cis |
NA |
| Forced vital capacity (FVC) |
-0.0148 |
0.00681 |
0.0298 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R14 Flatulence and related conditions |
0.464 |
0.231 |
0.0446 |
Wald ratio |
1 |
cis |
NA |
| Thalamus volume |
-42.6 |
23.6 |
0.0705 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K40 Inguinal hernia |
-0.102 |
0.0564 |
0.0708 |
Wald ratio |
1 |
cis |
NA |
| …and 61 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3450_4_2 |
Kallikrein 6 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
29 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 KLK10 levels |
2e-587 |
rs1654530 |
2 |
GCST90860356 |
no MR -> candidate analysis |
| KLK6/MOG protein level ratio |
6e-258 |
rs1654535 |
1 |
GCST90315255 |
no MR -> candidate analysis |
| Circulating KLK6 levels |
3e-241 |
rs268891 |
3 |
GCST90859992 |
no MR -> candidate analysis |
| KLK6/PTPRN2 protein level ratio |
5e-214 |
rs1654535 |
1 |
GCST90315256 |
no MR -> candidate analysis |
| KLK6 protein levels |
5e-191 |
rs268891 |
2 |
GCST90469705 |
no MR -> candidate analysis |
| Kallikrein-6 levels |
3e-99 |
rs268891 |
1 |
GCST90012008 |
no MR -> candidate analysis |
| KLK7 protein levels |
1e-80 |
rs56031098 |
2 |
GCST90469706 |
no MR -> candidate analysis |
| KLK10 protein levels |
2e-59 |
rs60850416 |
3 |
GCST90469696 |
no MR -> candidate analysis |
| Serum levels of protein KLK10 |
2e-57 |
rs57392237 |
1 |
GCST90089306 |
no MR -> candidate analysis |
| KLK12 protein levels |
3e-37 |
rs12461147 |
2 |
GCST90469698 |
no MR -> candidate analysis |
| KLK4 protein levels |
2e-29 |
rs57392237 |
1 |
GCST90469704 |
no MR -> candidate analysis |
| Erythematosquamous dermatosis (PheCode 690) |
4e-22 |
rs268890 |
2 |
GCST90480446 |
no MR -> candidate analysis |
| …and 7 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 280 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 |
| seborrheic dermatitis |
0.277 |
— |
common-variant locus |
no MR -> candidate analysis |
| erythematosquamous dermatosis |
0.274 |
— |
common-variant locus |
no MR -> candidate analysis |
| placenta praevia |
0.22 |
— |
common-variant locus |
no MR -> candidate analysis |
| alcohol drinking |
0.21 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 4 rows above, 4 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 (Kallikrein-6) |
| gnomAD constraint |
pLI=6.9e-05, LOEUF=1.12 — LoF-tolerant |
| GWAS Catalog |
163 unique SNPs / 424 rows |
| ClinVar |
52 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 280 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 ‘KLK6’ and resolved to ‘Kallikrein-6’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 52 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 19 of 19 traits by best p-value, aggregated from 29 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/Q92876 — 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/ENSG00000167755/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4448/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/KLK6 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/KLK6 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=KLK6%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/KLK6 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:24:42 · 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