| HGNC Family | Killer cell lectin-like receptors (KLR) |
| Name | killer cell lectin-like receptor subfamily F, member 2 |
| Description | Enables protein homodimerization activity. Predicted to be involved in natural killer cell degranulation and positive regulation of cytokine production. Predicted to act upstream of or within natural killer cell activation and positive regulation of natural killer cell mediated cytotoxicity. Located in plasma membrane. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KLRF2, which encodes the activating natural killer (NK) cell receptor NKp65, plays a critical role in immune surveillance by mediating NK cell activation upon binding its cognate ligand, keratinocyte‐associated C‐type lectin (KACL). Expression of KACL is largely restricted to skin cells—particularly keratinocytes—and this receptor–ligand pair represents a dedicated mechanism for the immunobiology of human skin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Structural studies have demonstrated that NKp65, although monomeric, binds the dimeric KACL with exceptionally high affinity. This unique binding mode underlies its potent capacity to trigger NK cell cytotoxicity and the release of proinflammatory cytokines through a signaling cascade that involves phosphorylation of a hem‐immunoreceptor tyrosine‐based activation motif (hemITAM) and a subsequent requirement for Syk kinase activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition to its well‐characterized role in skin immunity, transcriptomic network analyses suggest that KLRF2 may also contribute to broader immune responses, as evidenced by its identification as a hub gene in studies of SARS‐CoV‐2 infection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Finally, the close genetic linkage observed between NKp65/KLRF2 and its ligand KACL—as part of the natural killer gene complex—underscores the evolutionary conservation and coordinated regulation of these receptors in tissue‐specific immunosurveillance pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jessica Spreu, Sabrina Kuttruff, Veronika Stejfova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of C-type lectin-like receptors NKp65 and KACL facilitates dedicated immune recognition of human keratinocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0913108107"}], "href": "https://doi.org/10.1073/pnas.0913108107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20194751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20194751"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Björn Bauer, Jessica Spreu, Christina Rohe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/imm.12432"}], "href": "https://doi.org/10.1111/imm.12432"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25510854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25510854"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yili Li, Qian Wang, Sharon Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of NKp65 bound to its keratinocyte ligand reveals basis for genetically linked recognition in natural killer gene complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1303300110"}], "href": "https://doi.org/10.1073/pnas.1303300110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23803857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23803857"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Björn Bauer, Tanja Wotapek, Tobias Zöller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Activating C-type Lectin-like Receptor NKp65 Signals through a Hemi-immunoreceptor Tyrosine-based Activation Motif (hemITAM) and Spleen Tyrosine Kinase (Syk)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.759977"}], "href": "https://doi.org/10.1074/jbc.M116.759977"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28082678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28082678"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Basavaraj Vastrad, Chanabasayya Vastrad, Anandkumar Tengli "}, {"type": "b", "children": [{"type": "t", "text": "Identification of potential mRNA panels for severe acute respiratory syndrome coronavirus 2 (COVID-19) diagnosis and treatment using microarray dataset and bioinformatics methods."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "3 Biotech (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13205-020-02406-y"}], "href": "https://doi.org/10.1007/s13205-020-02406-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33251083"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33251083"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Olga Lysenko, Dorothea Schulte, Michel Mittelbronn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BACL is a novel brain-associated, non-NKC-encoded mammalian C-type lectin-like receptor of the CLEC2 family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0065345"}], "href": "https://doi.org/10.1371/journal.pone.0065345"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23776472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23776472"}]}]}]}
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| Synonyms | NKP65 |
| Proteins | KLRF2_HUMAN |
| NCBI Gene ID | 100431172 |
| 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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KLRF2 has 838 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 40 datasets.
Click the + buttons to view associations for KLRF2 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of KLRF2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of KLRF2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of KLRF2 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 KLRF2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing KLRF2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with KLRF2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of KLRF2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| dbGAP Gene-Trait Associations | traits associated with KLRF2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by KLRF2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with KLRF2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at KLRF2 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 KLRF2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of KLRF2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with KLRF2 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 KLRF2 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of KLRF2 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving KLRF2 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving KLRF2 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving KLRF2 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing KLRF2 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by KLRF2 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by KLRF2 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by KLRF2 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of KLRF2 gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of KLRF2 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 KLRF2 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with KLRF2 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| GWASdb SNP-Disease Associations | diseases associated with KLRF2 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
| GWASdb SNP-Phenotype Associations | phenotypes associated with KLRF2 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for KLRF2 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of KLRF2 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 KLRF2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Kinase Library Tyrosine Kinome Atlas | kinases that phosphorylate KLRF2 protein from the Kinase Library Tyrosine Kinome Atlas dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of KLRF2 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of KLRF2 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of KLRF2 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of KLRF2 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of KLRF2 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of KLRF2 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with KLRF2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
