CausalSentinel

Protein Dossier — KLRC3 (NKG2-E type II integral membrane protein)

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
Non-cancer illness code self-reported: hypopituitarism 0.624 0.188 8.73e-04 Wald ratio 1 trans NA
Non-cancer illness code self-reported: osteoporosis 0.106 0.0447 0.0173 Wald ratio 1 trans NA
Alcohol intake frequency -0.0204 0.00915 0.0257 Wald ratio 1 trans NA
Diagnoses - main ICD10: R35 Polyuria -0.293 0.136 0.0309 Wald ratio 1 trans NA
Thalamus volume 38 17.8 0.0325 Wald ratio 1 trans NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt -0.173 0.0822 0.0358 Wald ratio 1 trans NA
Hippocampus volume 27.1 13.4 0.0424 Wald ratio 1 trans NA
Non-cancer illness code self-reported: uterine fibroids -0.112 0.0561 0.0456 Wald ratio 1 trans NA
Endometrioid ovarian cancer -0.16 0.0803 0.047 Wald ratio 1 trans NA
Lumbar spine bone mineral density -0.0469 0.0237 0.0478 Wald ratio 1 trans NA
Weight -0.0104 0.00546 0.0558 Wald ratio 1 trans NA
Diagnoses - main ICD10: G47 Sleep disorders -0.186 0.0984 0.0581 Wald ratio 1 trans NA
…and 66 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

12 association rows across 12 traits (10 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
KLRK1 protein levels 2e-27 rs542584463 1 GCST90469713 no MR -> candidate analysis
monocyte (fraction, mean, inv-norm transformed) 4e-21 rs2682487 1 GCST90479705 no MR -> candidate analysis
Aspartate aminotransferase levels 5e-18 rs17513937 1 GCST90011899 no MR -> candidate analysis
platelet count (minimum, inv-norm transformed) 2e-16 rs2682487 1 GCST90476302 no MR -> candidate analysis
monocyte (fraction, maximum, inv-norm transformed) 4e-15 rs2682487 1 GCST90479704 no MR -> candidate analysis
monocyte (absolute count, maximum, inv-norm transformed) 1e-14 rs2859659 1 GCST90479701 no MR -> candidate analysis
Platelet count 2e-14 rs2859659 1 GCST90002361 no MR -> candidate analysis
Complex ventricular septal defect 3e-11 rs10734829 1 GCST90246230 no MR -> candidate analysis
Gamma glutamyl transferase levels 3e-11 rs17513937 1 GCST90662899 no MR -> candidate analysis
Mean corpuscular volume 5e-9 rs77926410 1 GCST004602 no MR -> candidate analysis
Neutrophil-to-lymphocyte ratio 5e-8 rs182561471 1 GCST90866310 no MR -> candidate analysis
Composite immunoglobulin trait (IgA/IgG) 3e-6 rs2682491 1 GCST008572 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 92 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
ventricular septal defect 0.44 common-variant locus no MR -> candidate analysis
psoriasis 0.337 common-variant locus MR: beta=0.0629, p=0.252 (trans)
Behcet disease 0.138 common-variant locus no MR -> candidate analysis

Of the 3 rows above, 2 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=0.00018, LOEUF=1.03 — LoF-tolerant
GWAS Catalog 85 unique SNPs / 170 rows
ClinVar 86 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance