KLRC3

Chr 12

killer cell lectin like receptor C3

Also known as: NKG2-E, NKG2E

NCBI Gene: 3823ENSG00000205810UniProt: Q07444

KLRC3 encodes NKG2E, a C-type lectin receptor expressed on natural killer (NK) cells and some cytotoxic T-cells that recognizes MHC class I HLA-E molecules and regulates immune cell function. This gene is not well-constrained against loss-of-function variants and is not currently associated with established Mendelian disease in pediatric patients.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
38
P/LP submissions
0%
P/LP missense
1.64
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— KLRC3
⚡
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 83 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.64LOEUF
pLI 0.000
Z-score 0.12
OE 0.96 (0.58–1.64)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.02Z-score
OE missense 1.01 (0.86–1.17)
118 obs / 117.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.96 (0.58–1.64)
0≤0.351.4
Missense OE1.01 (0.86–1.17)
0≤0.61.4
Synonymous OE1.25
0≤1.21.6
LoF obs/exp: 9 / 9.4Missense obs/exp: 118 / 117.4Syn Z: -1.21
DN
0.80top 10%
GOF
0.78top 25%
LOF
0.2190th %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

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic2
VUS30
Likely Benign4
Benign6
36
Pathogenic
2
Likely Pathogenic
30
VUS
4
Likely Benign
6
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
28
2
0
30
Likely Benign
0
4
0
0
4
Benign
2
4
0
0
6
Total23640078

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

View in ClinVar →

Protein Context — Lollipop Plot

KLRC3 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Machine learning and bioinformatics-based identification of mitophagy-related diagnostic biomarkers in bronchiolitis obliterans
Wang Y et al.·Medicine (Baltimore)
2026
Identification of immune hub genes participating in the pathogenesis and progression of Vogt-Koyanagi-Harada disease
Wang Y et al.·Front Immunol
2022
Tumor-infiltrating CD8+ sub-populations in primary and recurrent glioblastoma: An in-silico study
Abdoli Shadbad M et al.·Heliyon
2024
Regulation of KLRC and Ceacam gene expression by miR-141 supports cell proliferation and metastasis in cervical cancer cells.
Dabous E et al.·BMC Cancer
2024
Serum metabolism-transcriptomics investigated into the immunity of whey protein isolate-galacto-oligosaccharide conjugates after dynamic high-pressure microfluidics pretreatment.
Mao JH et al.·Food Res Int
2024
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Immunoprognostic model of lung adenocarcinoma and screening of sensitive drugs.
Liang P et al.·Sci Rep
2022Functional
Identification of MARK2, CCDC71, GATA2, and KLRC3 as candidate diagnostic genes and potential therapeutic targets for repeated implantation failure with antiphospholipid syndrome by integrated bioinformatics analysis and machine learning.
Zhang M et al.·Front Immunol
2023
Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate.
Park H et al.·Lab Invest
2018
Identifying novel biomarkers for systemic lupus erythematosus associated with macrophage activation syndrome.
Pei Y et al.·Biomed Pharmacother
2026
Differentially expressed gene transcripts using RNA sequencing from the blood of immunosuppressed kidney allograft recipients.
Dorr C et al.·PLoS One
2015
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients