Protein Dossier — KLK8 (Kallikrein-8)
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 |
| Sodium in urine |
0.0218 |
0.00618 |
4.09e-04 |
Wald ratio |
1 |
cis |
NA |
| Forced vital capacity (FVC) |
-0.0152 |
0.00515 |
0.00315 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I84 Haemorrhoids |
0.105 |
0.0364 |
0.00373 |
Wald ratio |
1 |
cis |
NA |
| Potassium in urine |
0.0178 |
0.00637 |
0.00536 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0148 |
0.00544 |
0.00635 |
Wald ratio |
1 |
cis |
NA |
| Body mass index (BMI) |
0.0168 |
0.00628 |
0.00739 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: high cholesterol |
0.0383 |
0.0164 |
0.0193 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hayfever or allergic rhinitis |
0.0568 |
0.0244 |
0.02 |
Wald ratio |
1 |
cis |
NA |
| Creatinine (enzymatic) in urine |
0.0135 |
0.00601 |
0.0244 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: pernicious anaemia |
-0.402 |
0.18 |
0.0256 |
Wald ratio |
1 |
cis |
NA |
| Ovarian cancer |
-0.0856 |
0.044 |
0.0518 |
Wald ratio |
1 |
cis |
NA |
| Eye problems or disorders: Cataract |
0.0605 |
0.0324 |
0.0624 |
Wald ratio |
1 |
cis |
NA |
| …and 53 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2834_54_1 |
kallikrein 8 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
28 association rows across 15 traits (26 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 |
| KLK8/NECTIN4 protein level ratio |
2e-1363 |
rs74705037 |
1 |
GCST90315258 |
no MR -> candidate analysis |
| KLK11/KLK8 protein level ratio |
1e-1342 |
rs74705037 |
1 |
GCST90315254 |
no MR -> candidate analysis |
| KLK8/LY6D protein level ratio |
1e-1166 |
rs74705037 |
1 |
GCST90315257 |
no MR -> candidate analysis |
| Circulating KLK8 levels |
3e-1082 |
rs74705037 |
4 |
GCST90860020 |
no MR -> candidate analysis |
| Kallikrein-8 levels |
4e-150 |
rs74705037 |
3 |
GCST90248164 |
no MR -> candidate analysis |
| Kallikrein-8 levels (KLK8.13708.56.3) |
6e-58 |
rs74705037 |
3 |
GCST90241680 |
no MR -> candidate analysis |
| kallikrein-11 levels |
2e-50 |
rs1122466 |
1 |
GCST90012012 |
no MR -> candidate analysis |
| Kallikrein-8 (analyte X13708.56) levels |
8e-50 |
rs1722546 |
1 |
GCST90422316 |
no MR -> candidate analysis |
| KLK12 protein levels |
5e-35 |
rs74705037 |
4 |
GCST90469698 |
no MR -> candidate analysis |
| KLK7 protein levels |
7e-33 |
rs1722547 |
1 |
GCST90469706 |
no MR -> candidate analysis |
| Serum levels of protein KLK8 |
9e-23 |
rs10410942 |
1 |
GCST90088093 |
no MR -> candidate analysis |
| Blood protein levels |
2e-17 |
rs10410942 |
2 |
GCST006585 |
no MR -> candidate analysis |
| …and 3 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 263 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 |
| actinic keratosis |
0.526 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 1 rows above, 1 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-8) |
| gnomAD constraint |
pLI=7.6e-05, LOEUF=1 — LoF-tolerant |
| GWAS Catalog |
185 unique SNPs / 442 rows |
| ClinVar |
72 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 263 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 ‘KLK8’ and resolved to ‘Kallikrein-8’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 72 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 15 of 15 traits by best p-value, aggregated from 28 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/O60259 — 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/ENSG00000129455/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4812/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/KLK8 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/KLK8 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=KLK8%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/KLK8 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:25:25 · 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