KLRC2

Chr 12

killer cell lectin like receptor C2

Also known as: CD159c, NKG2-C, NKG2C

KLRC2 encodes an immune activating receptor that forms complexes with KLRD1 on natural killer cells and cytotoxic lymphocytes to recognize HLA-E molecules and regulate immune responses, particularly in viral infections and maternal-fetal tolerance. The gene is not highly constrained against loss-of-function variants and currently has no established disease associations in humans. KLRC2 functions primarily in immune system regulation rather than neurological processes.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
8
Pubs (1 yr)
38
P/LP submissions
0%
P/LP missense
1.81
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryKLRC2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 30 VUS of 80 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.81LOEUF
pLI 0.000
Z-score -0.64
OE 1.21 (0.781.81)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.27Z-score
OE missense 1.07 (0.931.24)
125 obs / 116.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.21 (0.781.81)
00.351.4
Missense OE1.07 (0.931.24)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 13 / 10.8Missense obs/exp: 125 / 116.8Syn Z: -0.21
DN
0.80top 25%
GOF
0.77top 25%
LOF
0.2189th %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

80 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic2
VUS30
Likely Benign5
Benign4
36
Pathogenic
2
Likely Pathogenic
30
VUS
5
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
2
0
2
VUS
0
27
3
0
30
Likely Benign
0
4
1
0
5
Benign
0
3
0
1
4
Total03442177

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KLRC2 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →