KIR2DS4 Gene

HGNC Family CD molecules (CD), Killer cell immunoglobulin-like receptors (KIR), Immunoglobulin superfamily domain containing
Name killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 4
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": "\nKIR2DS4 is one of the oldest and most prevalent activating receptors expressed on human natural killer (NK) cells. It functions as a histocompatibility leukocyte antigen (HLA) class I receptor with a unique ligand specificity that distinguishes it from other killer-cell immunoglobulin-like receptors. KIR2DS4 recognizes particular subsets of HLA-C, in addition to HLA-A*11, with its specificity largely determined by a distinctive proline–valine motif at positions 71–72 that alters its binding loop and bonding potential. Site‐directed mutagenesis and crystallographic studies have underscored the importance of these residues, thereby defining the receptor’s unique interaction with its HLA ligands."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its molecular specificity, KIR2DS4 plays a significant role in shaping NK cell responses, particularly in the context of viral infections. Studies have demonstrated that activating KIRs, including KIR2DS4 alongside KIR2DS2 and KIR3DS1, contribute to the clonal-like expansion and differentiation of NK cells during human cytomegalovirus infection. This expansion is thought to be driven by education via self-specific inhibitory KIRs as well as the concerted action of activating receptors, positioning KIR2DS4 as an important mediator in the adaptation of the NK cell compartment to viral challenges."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thorsten Graef, Achim K Moesta, Paul J Norman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-C."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20091010"}], "href": "https://doi.org/10.1084/jem.20091010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19858347"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19858347"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Vivien Béziat, Lisa L Liu, Jenny-Ann Malmberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-10-459545"}], "href": "https://doi.org/10.1182/blood-2012-10-459545"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23325834"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23325834"}]}]}]}
Synonyms NKAT8, KIR412, KIR-2DS4, KIR1D, CD158I, KKA3, NKAT-8
Proteins KI2S4_HUMAN
NCBI Gene ID 3809
API
Download Associations
Predicted Functions View KIR2DS4's ARCHS4 Predicted Functions.
Co-expressed Genes View KIR2DS4's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View KIR2DS4's ARCHS4 Predicted Functions.

Functional Associations

KIR2DS4 has 1,947 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 64 datasets.

Click the + buttons to view associations for KIR2DS4 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 KIR2DS4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of KIR2DS4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of KIR2DS4 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 KIR2DS4 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 KIR2DS4 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 KIR2DS4 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 KIR2DS4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with KIR2DS4 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 KIR2DS4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of KIR2DS4 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 KIR2DS4 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 KIR2DS4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing KIR2DS4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with KIR2DS4 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 KIR2DS4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with KIR2DS4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores diseases associated with KIR2DS4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with KIR2DS4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DisGeNET Gene-Disease Associations diseases associated with KIR2DS4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with KIR2DS4 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 KIR2DS4 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 KIR2DS4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of KIR2DS4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
GAD Gene-Disease Associations diseases associated with KIR2DS4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with KIR2DS4 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 KIR2DS4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with KIR2DS4 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 KIR2DS4 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of KIR2DS4 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 KIR2DS4 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 KIR2DS4 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 KIR2DS4 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 KIR2DS4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving KIR2DS4 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Cellular Component Annotations 2015 cellular components containing KIR2DS4 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by KIR2DS4 gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by KIR2DS4 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of KIR2DS4 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 KIR2DS4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of KIR2DS4 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with KIR2DS4 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
GWASdb SNP-Disease Associations diseases associated with KIR2DS4 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with KIR2DS4 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with KIR2DS4 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for KIR2DS4 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of KIR2DS4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of KIR2DS4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
KEGG Pathways pathways involving KIR2DS4 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 KIR2DS4 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 KIR2DS4 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 KIR2DS4 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LOCATE Curated Protein Localization Annotations cellular components containing KIR2DS4 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain KIR2DS4 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MSigDB Cancer Gene Co-expression Modules co-expressed genes for KIR2DS4 from the MSigDB Cancer Gene Co-expression Modules dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for KIR2DS4 from the Pathway Commons Protein-Protein Interactions dataset.
Reactome Pathways 2014 pathways involving KIR2DS4 protein from the Reactome Pathways dataset.
Reactome Pathways 2024 pathways involving KIR2DS4 protein from the Reactome Pathways 2024 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of KIR2DS4 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of KIR2DS4 gene from the RummaGEO Gene Perturbation Signatures dataset.
Tabula Sapiens Gene-Cell Associations cell types with high or low expression of KIR2DS4 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of KIR2DS4 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 KIR2DS4 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 KIR2DS4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with KIR2DS4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.