KLRK1
Chr 12killer cell lectin like receptor K1
Also known as: CD314, D12S2489E, KLR, NKG2-D, NKG2D
The protein functions as an activating receptor on natural killer (NK) cells and CD8+ T cells that recognizes stress-induced ligands on tumor cells and virus-infected cells, triggering cytotoxic immune responses and TNF expression. Mutations in this gene cause immunodeficiency with severe reduction in NK- and T-cell function and susceptibility to viral infections, following autosomal recessive inheritance. The gene shows low constraint to loss-of-function variation, consistent with the recessive inheritance pattern observed in affected patients.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
45 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 36 |
Likely Pathogenic | — | — | — | — | 2 |
VUS | — | — | — | — | 5 |
Likely Benign | — | — | — | — | 1 |
Benign | — | — | — | — | 1 |
| Total | — | 45 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KLRK1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools