KLRC1

Chr 12

killer cell lectin like receptor C1

Also known as: CD159A, NKG2, NKG2A

The KLRC1 protein functions as an immune inhibitory receptor that forms complexes with KLRD1 to recognize HLA-E molecules, enabling natural killer cells and T cells to distinguish self from non-self and prevent autoimmune responses. This gene is loss-of-function tolerant (pLI = 0.00004, LOEUF = 1.31), and mutations are not currently associated with established Mendelian disease phenotypes despite its role in immune regulation. The gene's tolerance to loss-of-function variants suggests that KLRC1 deficiency may not cause severe developmental or immunological disorders in humans.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
21
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.31
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryKLRC1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.31LOEUF
pLI 0.000
Z-score 0.84
OE 0.73 (0.421.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.07Z-score
OE missense 1.02 (0.881.18)
122 obs / 119.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.73 (0.421.31)
00.351.4
Missense OE1.02 (0.881.18)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 8 / 11.0Missense obs/exp: 122 / 119.8Syn Z: 0.68
DN
0.82top 10%
GOF
0.74top 25%
LOF
0.2091th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KLRC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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