| HGNC Family | CD molecules (CD), Immunoglobulin superfamily domain containing |
| Name | B and T lymphocyte associated |
| Description | This gene encodes a member of the immunoglobulin superfamily. The encoded protein contains a single immunoglobulin (Ig) domain and is a receptor that relays inhibitory signals to suppress the immune response. Alternative splicing results in multiple transcript variants. Polymorphisms in this gene have been associated with an increased risk of rheumatoid arthritis. [provided by RefSeq, Aug 2011] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BTLA (B and T Lymphocyte Attenuator) is an immunoglobulin‐domain receptor that is not expressed on naive T cells but is induced upon activation—particularly on T helper type 1 cells—and functions as a key negative regulator of T cell responses by attenuating receptor‐mediated activation signals (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Upon engagement, BTLA becomes tyrosine‐phosphorylated and recruits phosphatases such as SHP-1 and SHP-2, leading to diminished production of cytokines like interleukin-2 and reduced cellular proliferation. Structural studies have demonstrated that BTLA binds uniquely to the herpesvirus entry mediator (HVEM) through its N-terminal cysteine-rich domain, establishing a receptor–ligand pair that is distinct from other CD28 family members (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, BTLA is capable of both trans interactions—with BTLA on one cell engaging HVEM on an adjacent cell—and cis interactions on the same cell surface, the latter of which can restrict HVEM activation and help maintain T cell quiescence (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In the context of tumors, BTLA is upregulated on antigen-specific CD8⁺ T cells and is associated with a state of partial dysfunction or exhaustion; combined blockade of BTLA along with other inhibitory pathways can enhance T cell proliferation, cytokine production, and antitumor responses (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, these findings underscore BTLA’s integral role in modulating T cell activation, survival, and immune tolerance in both physiological and pathological conditions, suggesting that therapeutic manipulation of the BTLA–HVEM axis could be beneficial in contexts such as autoimmunity and cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Norihiko Watanabe, Maya Gavrieli, John R Sedy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni944"}], "href": "https://doi.org/10.1038/ni944"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12796776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12796776"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "John R Sedy, Maya Gavrieli, Karen G Potter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni1144"}], "href": "https://doi.org/10.1038/ni1144"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15568026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15568026"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Deanne M Compaan, Lino C Gonzalez, Irene Tom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Attenuating lymphocyte activity: the crystal structure of the BTLA-HVEM complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M507629200"}], "href": "https://doi.org/10.1074/jbc.M507629200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16169851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16169851"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Timothy C Cheung, Lisa M Oborne, Marcos W Steinberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "T cell intrinsic heterodimeric complexes between HVEM and BTLA determine receptivity to the surrounding microenvironment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0902490"}], "href": "https://doi.org/10.4049/jimmunol.0902490"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19915044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19915044"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Julien Fourcade, Zhaojun Sun, Ornella Pagliano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-11-2637"}], "href": "https://doi.org/10.1158/0008-5472.CAN-11-2637"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22205715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22205715"}]}]}]}
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| Synonyms | CD272, BTLA1 |
| Proteins | BTLA_HUMAN |
| NCBI Gene ID | 151888 |
| 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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BTLA has 4,603 functional associations with biological entities spanning 7 categories (molecular profile, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 91 datasets.
Click the + buttons to view associations for BTLA from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles | tissues with high or low expression of BTLA gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of BTLA 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 Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of BTLA gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| BioGPS Mouse Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of BTLA gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of BTLA 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 BTLA gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with BTLA 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 BTLA gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of BTLA 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 BTLA 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 BTLA gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing BTLA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with BTLA protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with BTLA 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 BTLA gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with BTLA gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| dbGAP Gene-Trait Associations | traits associated with BTLA 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 BTLA gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with BTLA 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 BTLA 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 BTLA 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 BTLA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with BTLA 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 BTLA 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 BTLA gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of BTLA 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 BTLA from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GAD Gene-Disease Associations | diseases associated with BTLA gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
| GAD High Level Gene-Disease Associations | diseases associated with BTLA gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with BTLA 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 BTLA from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of BTLA 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 BTLA 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 BTLA 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 BTLA gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of BTLA gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving BTLA gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving BTLA gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving BTLA gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing BTLA protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by BTLA gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of BTLA 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 BTLA 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 BTLA gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
| GTEx Tissue-Specific Aging Signatures | tissue samples with high or low expression of BTLA gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with BTLA gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| GWASdb SNP-Disease Associations | diseases associated with BTLA gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
| GWASdb SNP-Phenotype Associations | phenotypes associated with BTLA gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of BTLA gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HPA Cell Line Gene Expression Profiles | cell lines with high or low expression of BTLA gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of BTLA gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Protein Expression Profiles | tissues with high or low expression of BTLA protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of BTLA gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| Hub Proteins Protein-Protein Interactions | interacting hub proteins for BTLA from the curated Hub Proteins Protein-Protein Interactions dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with BTLA gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for BTLA protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of BTLA gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of BTLA gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of BTLA 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 BTLA 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 BTLA 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 BTLA gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Curated Protein Localization Annotations | cellular components containing BTLA 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 BTLA protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by BTLA gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MiRTarBase microRNA Targets | microRNAs targeting BTLA gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset. | |
| MoTrPAC Rat Endurance Exercise Training | tissue samples with high or low expression of BTLA gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset. | |
| MPO Gene-Phenotype Associations | phenotypes of transgenic mice caused by BTLA gene mutations from the MPO Gene-Phenotype Associations dataset. | |
| MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of BTLA gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for BTLA from the Pathway Commons Protein-Protein Interactions dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of BTLA gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of BTLA gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving BTLA protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving BTLA protein from the Wikipathways PFOCR 2024 dataset. | |
| Reactome Pathways 2014 | pathways involving BTLA protein from the Reactome Pathways dataset. | |
| Reactome Pathways 2024 | pathways involving BTLA protein from the Reactome Pathways 2024 dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at BTLA gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of BTLA gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of BTLA gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of BTLA gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of BTLA gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of BTLA gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of BTLA 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 BTLA 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 BTLA protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of BTLA protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of BTLA protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with BTLA protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with BTLA protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
| WikiPathways Pathways 2014 | pathways involving BTLA protein from the Wikipathways Pathways 2014 dataset. | |
| WikiPathways Pathways 2024 | pathways involving BTLA protein from the WikiPathways Pathways 2024 dataset. | |
