HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
KLRC4
killer cell lectin like receptor C4
Chromosome 12 · 12p13.2
NCBI Gene: 8302Ensembl: ENSG00000183542.7HGNC: HGNC:6377UniProt: O43908
27PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
activating MHC class Ib receptor activitystimulatory C-type lectin receptor signaling pathwaynatural killer cell mediated immunitypositive regulation of natural killer cell mediated cytotoxicityBehcet's syndromeneurodegenerative diseaseisolated agammaglobulinemiapsoriasis
✦AI Summary

KLRC4 encodes a killer cell lectin-like receptor involved in natural killer (NK) cell-mediated immunity. As an activating MHC class Ib receptor, KLRC4 recognizes HLA-E molecules on target cells, facilitating positive regulation of NK cell-mediated cytotoxicity through stimulatory C-type lectin receptor signaling 1. The receptor functions as part of the KLRC4-KLRK1 axis, where KLRC4 cooperates with NKG2D (encoded by KLRK1) to recognize ligands on stressed or infected cells 2. Clinically, KLRC4 genetic variants are associated with multiple inflammatory and autoimmune conditions. KLRC4 polymorphisms, particularly rs2617170 (p.Asn104Ser) and rs2734565, show strong associations with Behçet's disease susceptibility across multiple populations 345. The rs2617170-T allele and rs2734565-C allele represent risk variants 34. Additionally, KLRC4 variants associate with antithyroid drug-induced agranulocytosis in Graves' disease patients, with rs2734565-C carriers experiencing significantly accelerated disease onset 2. KLRC4 has also been identified as a potential biomarker in ST-elevation myocardial infarction 6. These associations suggest KLRC4 polymorphisms modulate NK cell immune responses relevant to vasculitic and inflammatory pathogenesis.

Sources cited
1
KLRC4 is recognized as a BD susceptibility gene encoding a killer cell lectin-like receptor family member involved in immunogenetics
PMID: 30341905
2
KLRC4-KLRK1 polymorphisms, particularly rs2734565, associate with susceptibility and progression of antithyroid drug-induced agranulocytosis, with rs2734565-C allele showing faster disease onset
PMID: 38237612
3
KLRC4 SNP rs2617170 (p.Asn104Ser) is nominally associated with Behçet's disease with OR 0.76 for T allele in meta-analysis
PMID: 26097239
4
KLRC4 rs2617170 TT genotype and loss of C allele/CC genotype are susceptibility factors for Behçet's disease in Chinese Han population; polymorphism affects KLRC4 protein stability and expression
PMID: 28706259
5
KLRC4 is identified as a genome-wide significant susceptibility locus for Behçet's disease alongside other immune-related genes
PMID: 33258398
6
KLRC4 is identified as a candidate biomarker for ST-elevation myocardial infarction with high sensitivity and specificity in predicting disease
PMID: 38597542
7
KLRC4 is associated with Behçet's disease susceptibility in genetic association studies
PMID: 25405820
Disease Associationsⓘ20
Behcet's syndromeOpen Targets
0.28Weak
neurodegenerative diseaseOpen Targets
0.28Weak
isolated agammaglobulinemiaOpen Targets
0.06Suggestive
psoriasisOpen Targets
0.06Suggestive
T-B+ severe combined immunodeficiency due to JAK3 deficiencyOpen Targets
0.05Suggestive
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positiveOpen Targets
0.05Suggestive
X-linked lymphoproliferative diseaseOpen Targets
0.05Suggestive
combined immunodeficiency due to ZAP70 deficiencyOpen Targets
0.05Suggestive
Chronic mucocutaneous candidosisOpen Targets
0.05Suggestive
Immunodeficiency by defective expression of HLA class 2Open Targets
0.05Suggestive
activated PI3K-delta syndromeOpen Targets
0.05Suggestive
gamma chain deficiencyOpen Targets
0.05Suggestive
combined immunodeficiency due to DOCK8 deficiencyOpen Targets
0.05Suggestive
X-Linked Combined Immunodeficiency DiseasesOpen Targets
0.05Suggestive
immunodeficiency 102Open Targets
0.04Suggestive
immunodeficiency 18Open Targets
0.04Suggestive
hyper-IgE recurrent infection syndrome 5, autosomal recessiveOpen Targets
0.04Suggestive
Cryptosporidiosis - chronic cholangitis - liver diseaseOpen Targets
0.04Suggestive
cryptosporidiosis-chronic cholangitis-liver disease syndromeOpen Targets
0.04Suggestive
immunodeficiency 89 and autoimmunityOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HLA-AProtein interaction97%HLA-EProtein interaction97%HLA-GProtein interaction97%KIR2DL1Protein interaction97%KIR2DL3Protein interaction97%KIR2DS5Protein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
33%
Liver
14%
Brain
11%
Ovary
5%
Heart
0%
Gene Interaction Network
Click a node to explore
KLRC4HLA-AHLA-EHLA-GKIR2DL1KIR2DL3KIR2DS5
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O43908
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.91LoF Tolerant
pLIⓘ
0.11Tolerant
Observed/Expected LoF0.48 [0.27–0.91]
RankingsWhere KLRC4 stands among ~20K protein-coding genes
  • #12,592of 20,598
    Most Researched27
  • #8,298of 17,882
    Most Constrained (LOEUF)0.91
Genes detectedKLRC4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genetics of vasculitis.
PMID: 25405820
Curr Opin Rheumatol · 2015
1.00
2
Novel Association of KLRC4-KLRK1 Gene Polymorphisms with Susceptibility and Progression of Antithyroid Drug-Induced Agranulocytosis.
PMID: 38237612
Exp Clin Endocrinol Diabetes · 2024
0.90
3
Brief report: association of CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 With Behçet's disease in Iranians.
PMID: 26097239
Arthritis Rheumatol · 2015
0.80
4
Behçet's disease: An immunogenetic perspective.
PMID: 30341905
J Cell Physiol · 2019
0.70
5
A comprehensive overview on the genetics of Behçet's disease.
PMID: 33258398
Int Rev Immunol · 2022
0.60