| HGNC Family | Immunoglobulin superfamily domain containing, Killer cell immunoglobulin-like receptors (KIR), CD molecules (CD) |
| Name | killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 1 |
| 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": "\n KIR2DL1 is an inhibitory killer‐cell immunoglobulin–like receptor that is predominantly expressed on natural killer (NK) cells and plays a critical role in regulating their effector functions. This receptor specifically recognizes human leukocyte antigen (HLA)–C allotypes of the C2 group, and its binding is exquisitely sensitive to peptide–dependent variations. In this context, KIR2DL1 serves as the inhibitory counterpart to activating receptors (such as KIR2DS1), sharing similar peptide sensitivity but differing in downstream signaling. Engagement of KIR2DL1 with its HLA‐C2 ligands recruits intracellular phosphatases via immunoreceptor tyrosine–based inhibitory motifs, thereby raising the activation threshold and dampening NK cell–mediated cytotoxicity. This inhibitory mechanism is essential for maintaining self–tolerance and modulating immune responses during viral infections, autoimmune disorders, and conditions related to pregnancy, where proper placentation is influenced by a balance between activating and inhibitory signals. Additionally, allelic polymorphism as well as variable cell–surface expression of KIR2DL1 contribute to differences in functional outcomes and disease susceptibility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "C Andrew Stewart, Fanny Laugier-Anfossi, Frédéric Vély, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0503594102"}], "href": "https://doi.org/10.1073/pnas.0503594102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16141329"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16141329"}]}, {"type": "r", "ref": 2, "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": 3, "children": [{"type": "t", "text": "Shiqiu Xiong, Andrew M Sharkey, Philippa R Kennedy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI68991"}], "href": "https://doi.org/10.1172/JCI68991"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24091323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24091323"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Wioleta Łuszczek, Maria Mańczak, Maria Cisło, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene for the activating natural killer cell receptor, KIR2DS1, is associated with susceptibility to psoriasis vulgaris."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Immunol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humimm.2004.05.008"}], "href": "https://doi.org/10.1016/j.humimm.2004.05.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15310528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15310528"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wing Leung, Rekha Iyengar, Brandon Triplett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparison of killer Ig-like receptor genotyping and phenotyping for selection of allogeneic blood stem cell donors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.174.10.6540"}], "href": "https://doi.org/10.4049/jimmunol.174.10.6540"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15879158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15879158"}]}]}]}
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| Synonyms | KIR-K64, NKAT-1, CD158A, P58.1, NKAT, KIR2DL3, KIR221, NKAT1 |
| Proteins | KI2L1_HUMAN |
| NCBI Gene ID | 3802 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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KIR2DL1 has 2,596 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 70 datasets.
Click the + buttons to view associations for KIR2DL1 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Achilles Cell Line Gene Essentiality Profiles | cell lines with fitness changed by KIR2DL1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of KIR2DL1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of KIR2DL1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Cell Line Gene Expression Profiles | cell lines with high or low expression of KIR2DL1 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 KIR2DL1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of KIR2DL1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| CCLE Cell Line Gene Expression Profiles | cell lines with high or low expression of KIR2DL1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with KIR2DL1 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 KIR2DL1 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of KIR2DL1 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 KIR2DL1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of KIR2DL1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of KIR2DL1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing KIR2DL1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with KIR2DL1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of KIR2DL1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with KIR2DL1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| CTD Gene-Chemical Interactions | chemicals interacting with KIR2DL1 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by KIR2DL1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DGIdb Drug Targets 2026 | interacting drugs for KIR2DL1 protein from the DGIdb Drug Targets 2026 dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with KIR2DL1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with KIR2DL1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with KIR2DL1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with KIR2DL1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with KIR2DL1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at KIR2DL1 gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of KIR2DL1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of KIR2DL1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| ESCAPE Omics Signatures of Genes and Proteins for Stem Cells | PubMedIDs of publications reporting gene signatures containing KIR2DL1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GAD Gene-Disease Associations | diseases associated with KIR2DL1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
| GAD High Level Gene-Disease Associations | diseases associated with KIR2DL1 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 KIR2DL1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with KIR2DL1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing KIR2DL1 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of KIR2DL1 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 KIR2DL1 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 KIR2DL1 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 KIR2DL1 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 KIR2DL1 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving KIR2DL1 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving KIR2DL1 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing KIR2DL1 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by KIR2DL1 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of KIR2DL1 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of KIR2DL1 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of KIR2DL1 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of KIR2DL1 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| Hub Proteins Protein-Protein Interactions | interacting hub proteins for KIR2DL1 from the curated Hub Proteins Protein-Protein Interactions dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with KIR2DL1 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for KIR2DL1 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of KIR2DL1 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| KEGG Pathways | pathways involving KIR2DL1 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 KIR2DL1 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of KIR2DL1 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of KIR2DL1 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain KIR2DL1 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MSigDB Cancer Gene Co-expression Modules | co-expressed genes for KIR2DL1 from the MSigDB Cancer Gene Co-expression Modules dataset. | |
| MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of KIR2DL1 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for KIR2DL1 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving KIR2DL1 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving KIR2DL1 protein from the Wikipathways PFOCR 2024 dataset. | |
| Phosphosite Textmining Biological Term Annotations | biological terms co-occuring with KIR2DL1 protein in abstracts of publications describing phosphosites from the Phosphosite Textmining Biological Term Annotations dataset. | |
| Reactome Pathways 2014 | pathways involving KIR2DL1 protein from the Reactome Pathways dataset. | |
| Reactome Pathways 2024 | pathways involving KIR2DL1 protein from the Reactome Pathways 2024 dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of KIR2DL1 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of KIR2DL1 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of KIR2DL1 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of KIR2DL1 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of KIR2DL1 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with KIR2DL1 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
