| HGNC Family | BPI fold containing (BPIF) |
| Name | BPI fold containing family B, member 4 |
| Description | Predicted to enable lipid binding activity. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BPIFB4 is emerging as a multifunctional protein that plays a critical role in maintaining vascular homeostasis and promoting healthy aging. In its longevity‐associated variant (LAV), BPIFB4 enhances endothelial nitric oxide synthase (eNOS) activity via phosphorylation and formation of a signaling complex with 14–3–3 and heat shock protein 90. This molecular cascade, further promoted by calcium mobilization and protein kinase Cα activation, improves vasorelaxation and vascular repair in response to mechanical stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Gene therapy studies in animal models have demonstrated that delivery of LAV‐BPIFB4 can rescue endothelial dysfunction, lower blood pressure, and reduce atherosclerotic disease progression—effects that are mediated partly by modulation of the CXCR4 signaling axis and by shifting monocyte/macrophage populations toward an anti‐inflammatory (M2) phenotype."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " Conversely, alternative BPIFB4 variants have been linked to impaired eNOS phosphorylation and hypertension, underscoring the importance of its specific isoforms in vascular regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Notably, high circulating levels of BPIFB4 characterize long‐living individuals and are associated with reduced frailty and enhanced reparative responses, suggesting that BPIFB4 may serve both as a biomarker and as a therapeutic target for counteracting age‐related cardiovascular and inflammatory disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francesco Villa, Albino Carrizzo, Chiara C Spinelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Analysis Reveals a Longevity-Associated Protein Modulating Endothelial Function and Angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.117.305875"}], "href": "https://doi.org/10.1161/CIRCRESAHA.117.305875"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26034043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26034043"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chiara Carmela Spinelli, Albino Carrizzo, Anna Ferrario, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LAV-BPIFB4 isoform modulates eNOS signalling through Ca2+/PKC-alpha-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvx072"}], "href": "https://doi.org/10.1093/cvr/cvx072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28419216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28419216"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Annibale Alessandro Puca, Albino Carrizzo, Chiara Spinelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Heart J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/eurheartj/ehz459"}], "href": "https://doi.org/10.1093/eurheartj/ehz459"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31289820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31289820"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zexu Dang, Elisa Avolio, Anita C Thomas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF-1/CXCR4 signalling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Heart Fail (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ejhf.1840"}], "href": "https://doi.org/10.1002/ejhf.1840"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32384208"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32384208"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Elena Ciaglia, Valentina Lopardo, Francesco Montella, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " macrophages and NAD"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " decline."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-022-04535-z"}], "href": "https://doi.org/10.1038/s41419-022-04535-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35087020"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35087020"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Carmine Vecchione, Francesco Villa, Albino Carrizzo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A rare genetic variant of BPIFB4 predisposes to high blood pressure via impairment of nitric oxide signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-10341-x"}], "href": "https://doi.org/10.1038/s41598-017-10341-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28852218"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28852218"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Francesco Villa, Alberto Malovini, Albino Carrizzo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum BPIFB4 levels classify health status in long-living individuals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immun Ageing (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12979-015-0054-8"}], "href": "https://doi.org/10.1186/s12979-015-0054-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26675039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26675039"}]}]}]}
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| Synonyms | C20ORF186, RY2G5, LPLUNC4, DJ726C3.5 |
| Proteins | BPIB4_HUMAN |
| NCBI Gene ID | 149954 |
| 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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BPIFB4 has 1,261 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 64 datasets.
Click the + buttons to view associations for BPIFB4 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 BPIFB4 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 BPIFB4 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 BPIFB4 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 BPIFB4 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 BPIFB4 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 BPIFB4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of BPIFB4 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of BPIFB4 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 BPIFB4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing BPIFB4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing BPIFB4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with BPIFB4 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 BPIFB4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| CTD Gene-Chemical Interactions | chemicals interacting with BPIFB4 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by BPIFB4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores | diseases associated with BPIFB4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with BPIFB4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with BPIFB4 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 BPIFB4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with BPIFB4 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 BPIFB4 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 BPIFB4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of BPIFB4 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 BPIFB4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing BPIFB4 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of BPIFB4 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 BPIFB4 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 BPIFB4 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 BPIFB4 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 BPIFB4 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of BPIFB4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing BPIFB4 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2023 | cellular components containing BPIFB4 protein from the curated GO Cellular Component Annotations 2023 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing BPIFB4 protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by BPIFB4 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of BPIFB4 gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of BPIFB4 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 BPIFB4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with BPIFB4 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| GWASdb SNP-Disease Associations | diseases associated with BPIFB4 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
| GWASdb SNP-Phenotype Associations | phenotypes associated with BPIFB4 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of BPIFB4 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for BPIFB4 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of BPIFB4 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 BPIFB4 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 BPIFB4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of BPIFB4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| LOCATE Curated Protein Localization Annotations | cellular components containing BPIFB4 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 BPIFB4 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of BPIFB4 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles | drug perturbations changing expression of BPIFB4 gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
| NURSA Protein Complexes | protein complexs containing BPIFB4 protein recovered by IP-MS from the NURSA Protein Complexes dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of BPIFB4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| Reactome Pathways 2024 | pathways involving BPIFB4 protein from the Reactome Pathways 2024 dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at BPIFB4 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of BPIFB4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of BPIFB4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of BPIFB4 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of BPIFB4 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 BPIFB4 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 BPIFB4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of BPIFB4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with BPIFB4 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 BPIFB4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
