CausalSentinel

Protein Dossier — KLK10 (Kallikrein-10)

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
Body fat -0.213 0.0691 0.00203 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pneumothorax 0.471 0.195 0.0157 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma -0.0401 0.0178 0.024 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.139 0.0634 0.0286 Wald ratio 1 cis NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis -0.125 0.06 0.0378 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate -0.149 0.0741 0.0438 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine 0.0118 0.00583 0.0439 Wald ratio 1 cis NA
Cancer code self-reported: basal cell carcinoma -0.145 0.074 0.0502 Wald ratio 1 cis NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms -0.106 0.0553 0.0561 Wald ratio 1 cis NA
Diagnoses - main ICD10: R11 Nausea and vomiting 0.156 0.0836 0.0614 Wald ratio 1 cis NA
Eye problems or disorders: Diabetes related eye disease -0.175 0.0937 0.0622 Wald ratio 1 cis NA
Diagnoses - main ICD10: R14 Flatulence and related conditions 0.335 0.189 0.0767 Wald ratio 1 cis NA
…and 79 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

38 association rows across 29 traits (35 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 3e-2250 rs3760738 2 GCST90860356 no MR -> candidate analysis
KLK10/KLK11 protein level ratio 4e-1456 rs201982139 1 GCST90315253 no MR -> candidate analysis
Kallikrein-10 levels 4e-329 rs2569454 5 GCST90248155 no MR -> candidate analysis
Cerebrospinal fluid protein KLK10 levels 3e-199 rs77303625 1 GCST90944378 no MR -> candidate analysis
KLK10 protein levels 4e-154 rs145472676 2 GCST90469696 no MR -> candidate analysis
KLK12 protein levels 5e-122 rs117025461 1 GCST90469698 no MR -> candidate analysis
Serum levels of protein KLK10 2e-117 rs3760738 1 GCST90089306 no MR -> candidate analysis
Cerebrospinal fluid protein KLK11 levels 1e-87 rs2569451 1 GCST90944379 no MR -> candidate analysis
Blood protein levels in cardiovascular risk 7e-76 rs62115757 1 GCST009731 no MR -> candidate analysis
KLK14 protein levels 3e-62 rs7259451 1 GCST90469700 no MR -> candidate analysis
Blood protein levels 4e-54 rs2569454 1 GCST006585 no MR -> candidate analysis
CDSN/KLK8 protein level ratio 8e-52 rs3745535 1 GCST90313996 no MR -> candidate analysis
…and 17 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 203 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
obesity disorder 0.128 common-variant locus no MR -> candidate analysis
fracture of pelvis 0.106 common-variant locus no MR -> candidate analysis
arthropathy 0.078 common-variant locus no MR -> candidate analysis

Of the 3 rows above, 3 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=3e-10, LOEUF=1.45 — LoF-tolerant
GWAS Catalog 188 unique SNPs / 444 rows
ClinVar 84 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance