KIR2DL2 Gene

HGNC Family	CD molecules (CD), Immunoglobulin superfamily domain containing, Killer cell immunoglobulin-like receptors (KIR)
Name	killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 2
Description	Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several `framework` genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nKIR2DL2 is an inhibitory receptor expressed on natural killer (NK) cells that primarily recognizes HLA‐C group 1 ligands. However, detailed binding and mutagenesis studies have shown that certain allelic variants (for example, KIR2DL2001) exhibit broader specificity by also engaging select HLA‐C group 2 allotypes. Moreover, subtle variations in HLA‐presented epitopes – as demonstrated for an HIV‐1 p24 Gag peptide – can modulate the binding affinity of KIR2DL2, which in turn can alter its capacity to inhibit NK cell cytotoxicity and even facilitate viral escape from immune surveillance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the setting of viral infections, the functional impact of KIR2DL2 is underscored by genetic studies in hepatitis C virus–infected patients, where an increased frequency of the KIR2DL2 gene – and particularly the homozygous KIR2DL2/KIR2DL2 genotype – is associated with nonresponse to antiviral therapy. In this regard, heightened inhibitory signaling through KIR2DL2 appears to impair effective viral clearance. In addition, epigenetic control mechanisms regulate its expression in T cells; promoter demethylation leads to enhanced transcription of KIR2DL2, affecting downstream signaling events and contributing, in synergy with T cell responses, to the overall HLA class I–restricted antiviral immunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOutside of direct antiviral responses, KIR2DL2 interactions with its HLA ligands also contribute to immune regulation in other clinical settings. For example, specific combinations of KIR2DL2 with HLA‐C1 have been linked to an altered risk profile in type 1 diabetes, highlighting its role as a critical checkpoint in modulating both NK cell and T cell functions. In addition, evidence from multiple sclerosis patients indicates that upregulation of KIR2DL2—particularly following viral challenges—may lead to reduced NK cell degranulation and cytotoxicity, further emphasizing its capacity to tune immune responses in autoimmune and inflammatory conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Achim K Moesta, Paul J Norman, Makoto Yawata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.180.6.3969"}], "href": "https://doi.org/10.4049/jimmunol.180.6.3969"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18322206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18322206"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nienke H van Teijlingen, Angelique Hölzemer, Christian Körner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sequence variations in HIV-1 p24 Gag-derived epitopes can alter binding of KIR2DL2 to HLA-C03:04 and modulate primary natural killer cell function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "AIDS (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/QAD.0000000000000284"}], "href": "https://doi.org/10.1097/QAD.0000000000000284"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24785948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24785948"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "M E Gutiérrez-Rodríguez, L Sandoval-Ramírez, M Díaz-Flores, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KIR gene in ethnic and Mestizo populations from Mexico."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humimm.2005.11.007"}], "href": "https://doi.org/10.1016/j.humimm.2005.11.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16698429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16698429"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ying Liu, Rork Kuick, Samir Hanash, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA methylation inhibition increases T cell KIR expression through effects on both promoter methylation and transcription factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.clim.2008.08.009"}], "href": "https://doi.org/10.1016/j.clim.2008.08.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18945643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18945643"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nafisa-Katrin Seich Al Basatena, Aidan Macnamara, Alison M Vine, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KIR2DL2 enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1002270"}], "href": "https://doi.org/10.1371/journal.ppat.1002270"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22022261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22022261"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "J R Vidal-Castiñeira, A López-Vázquez, R Díaz-Peña, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of killer immunoglobulin-like receptors in the response to combined treatment in patients with chronic hepatitis C virus infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.01285-09"}], "href": "https://doi.org/10.1128/JVI.01285-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19846535"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19846535"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "A Shastry, S K Sedimbi, R Rajalingam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combination of KIR 2DL2 and HLA-C1 (Asn 80) confers susceptibility to type 1 diabetes in Latvians."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Immunogenet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1744-313X.2008.00804.x"}], "href": "https://doi.org/10.1111/j.1744-313X.2008.00804.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19046302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19046302"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Roberta Rizzo, Valentina Gentili, Ilaria Casetta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered natural killer cells' response to herpes virus infection in multiple sclerosis involves KIR2DL2 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuroimmunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jneuroim.2012.07.004"}], "href": "https://doi.org/10.1016/j.jneuroim.2012.07.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22871633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22871633"}]}]}]}
Synonyms	CD158b, P58.2, CD158B1, NKAT6, NKAT-6
Proteins	KI2L2_HUMAN
NCBI Gene ID	3803
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KIR2DL2 has 1,066 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 40 datasets.

Click the + buttons to view associations for KIR2DL2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KIR2DL2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by KIR2DL2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of KIR2DL2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of KIR2DL2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KIR2DL2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of KIR2DL2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KIR2DL2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of KIR2DL2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of KIR2DL2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KIR2DL2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KIR2DL2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KIR2DL2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with KIR2DL2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DisGeNET Gene-Disease Associations	diseases associated with KIR2DL2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KIR2DL2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	GAD Gene-Disease Associations	diseases associated with KIR2DL2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with KIR2DL2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of KIR2DL2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with KIR2DL2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of KIR2DL2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of KIR2DL2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of KIR2DL2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of KIR2DL2 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
	GEO Signatures of Differentially Expressed Genes for Viral Infections	virus perturbations changing expression of KIR2DL2 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
	GO Biological Process Annotations 2015	biological processes involving KIR2DL2 gene from the curated GO Biological Process Annotations 2015 dataset.
	GO Cellular Component Annotations 2015	cellular components containing KIR2DL2 protein from the curated GO Cellular Component Annotations 2015 dataset.
	Hub Proteins Protein-Protein Interactions	interacting hub proteins for KIR2DL2 from the curated Hub Proteins Protein-Protein Interactions dataset.
	HuGE Navigator Gene-Phenotype Associations	phenotypes associated with KIR2DL2 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
	InterPro Predicted Protein Domain Annotations	protein domains predicted for KIR2DL2 protein from the InterPro Predicted Protein Domain Annotations dataset.
	JASPAR Predicted Transcription Factor Targets	transcription factors regulating expression of KIR2DL2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
	KEGG Pathways	pathways involving KIR2DL2 protein from the KEGG Pathways dataset.
	Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles	cell lines with high or low copy number of KIR2DL2 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
	LOCATE Predicted Protein Localization Annotations	cellular components predicted to contain KIR2DL2 protein from the LOCATE Predicted Protein Localization Annotations dataset.
	Pathway Commons Protein-Protein Interactions	interacting proteins for KIR2DL2 from the Pathway Commons Protein-Protein Interactions dataset.
	PFOCR Pathway Figure Associations 2024	pathways involving KIR2DL2 protein from the Wikipathways PFOCR 2024 dataset.
	Reactome Pathways 2014	pathways involving KIR2DL2 protein from the Reactome Pathways dataset.
	Reactome Pathways 2024	pathways involving KIR2DL2 protein from the Reactome Pathways 2024 dataset.
	TargetScan Predicted Nonconserved microRNA Targets	microRNAs regulating expression of KIR2DL2 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
	TISSUES Curated Tissue Protein Expression Evidence Scores	tissues with high expression of KIR2DL2 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
	TISSUES Experimental Tissue Protein Expression Evidence Scores	tissues with high expression of KIR2DL2 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
	TISSUES Text-mining Tissue Protein Expression Evidence Scores	tissues co-occuring with KIR2DL2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.