| HGNC Family | Ion channels |
| Name | bestrophin 4 |
| Description | This gene is a member of the bestrophin gene family of anion channels. Bestrophin genes share a similar gene structure with highly conserved exon-intron boundaries, but with distinct 3' ends. Bestrophins are transmembrane proteins that contain a homologous region rich in aromatic residues, including an invariant arg-phe-pro motif. Mutation in one of the family members (bestrophin 1) is associated with vitelliform macular dystrophy. The bestrophin 4 gene is predominantly expressed in the colon. [provided by RefSeq, Jul 2008] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BEST4 is one of four human bestrophin paralogs that forms a Ca²⁺‐activated anion channel with notable permeability to both chloride (Cl⁻) and bicarbonate (HCO₃⁻) ions. Early electrophysiological studies show that BEST4 exhibits a relatively high HCO₃⁻ permeability and conductance similar to that for Cl⁻."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In excised membrane patch experiments, human BEST4 generates robust, Ca²⁺‐dependent Cl⁻ currents with a submicromolar affinity for Ca²⁺."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Furthermore, studies in mouse models indicate that the channel activity of mBest4 is subject to intrinsic regulation by an auto‐inhibitory motif in its C terminus, suggesting that gating of BEST4 can be modulated by intracellular structural elements."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the gastrointestinal tract, BEST4 is selectively expressed in absorptive epithelial cells of both the small intestine and colon, in contrast to BEST2, which is confined to colonic goblet cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Recent single‐cell transcriptomic analyses have further defined a distinct BEST4⁺ cell population within the human intestinal epithelium, underscoring its role as a lineage marker for specialized absorptive functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, emerging clinical studies have implicated BEST4 in colorectal cancer (CRC); high levels of BEST4 expression in CRC samples correlate with advanced tumor stage, lymph node metastasis, and poorer patient survival. Mechanistic investigations indicate that BEST4 may interact with the p85α regulatory subunit of PI3K, enhancing p110 kinase activity, which in turn activates Akt signaling and upregulates oncogenic drivers such as MYC and CCND1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, autoantibodies against intestinally expressed BEST4 have been detected in immune dysregulation syndromes like IPEX."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings establish BEST4 as a Ca²⁺‐activated anion channel that plays a crucial role in intestinal epithelial ion homeostasis and fluid transport, while also potentially contributing to colorectal carcinogenesis via modulation of PI3K/Akt signaling pathways.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhiqiang Qu, H Criss Hartzell "}, {"type": "b", "children": [{"type": "t", "text": "Bestrophin Cl- channels are highly permeable to HCO3-."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00398.2007"}], "href": "https://doi.org/10.1152/ajpcell.00398.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18400985"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18400985"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Takashi Tsunenari, Jeremy Nathans, King-Wai Yau "}, {"type": "b", "children": [{"type": "t", "text": "Ca2+-activated Cl- current from human bestrophin-4 in excised membrane patches."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gen Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1085/jgp.200609527"}], "href": "https://doi.org/10.1085/jgp.200609527"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16702355"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16702355"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhiqiang Qu, Yuanyuan Cui, Criss Hartzell "}, {"type": "b", "children": [{"type": "t", "text": "A short motif in the C-terminus of mouse bestrophin 3 [corrected] inhibits its activation as a Cl channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2006.03.025"}], "href": "https://doi.org/10.1016/j.febslet.2006.03.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16563389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16563389"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Go Ito, Ryuichi Okamoto, Tatsuro Murano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lineage-specific expression of bestrophin-2 and bestrophin-4 in human intestinal epithelial cells."}]}, {"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.0079693"}], "href": "https://doi.org/10.1371/journal.pone.0079693"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24223998"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24223998"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Joao M Serigado, Jennifer Foulke-Abel, William C Hines, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ulcerative Colitis: Novel Epithelial Insights Provided by Single Cell RNA Sequencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Med (Lausanne) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fmed.2022.868508"}], "href": "https://doi.org/10.3389/fmed.2022.868508"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35530046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35530046"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Joseph Burclaff, R Jarrett Bliton, Keith A Breau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Proximal-to-Distal Survey of Healthy Adult Human Small Intestine and Colon Epithelium by Single-Cell Transcriptomics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Gastroenterol Hepatol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jcmgh.2022.02.007"}], "href": "https://doi.org/10.1016/j.jcmgh.2022.02.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35176508"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35176508"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xiao-Shun He, Wen-Long Ye, Yu-Juan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogenic potential of BEST4 in colorectal cancer via activation of PI3K/Akt signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-021-02160-2"}], "href": "https://doi.org/10.1038/s41388-021-02160-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35058597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35058597"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sara E Vazquez, Sabrina A Mann, Aaron Bodansky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autoantibody discovery across monogenic, acquired, and COVID19-associated autoimmunity with scalable PhIP-Seq."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "bioRxiv (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/2022.03.23.485509"}], "href": "https://doi.org/10.1101/2022.03.23.485509"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35350199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35350199"}]}]}]}
|
| Synonyms | VMD2L2 |
| Proteins | BEST4_HUMAN |
| NCBI Gene ID | 266675 |
| API | |
| Download Associations | |
| Predicted Functions |
 |
| Co-expressed Genes |
|
| Expression in Tissues and Cell Lines |
|
BEST4 has 2,919 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 69 datasets.
Click the + buttons to view associations for BEST4 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of BEST4 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 BEST4 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 BEST4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq | tissue samples with high or low expression of BEST4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of BEST4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of BEST4 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 BEST4 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 BEST4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with BEST4 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 BEST4 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of BEST4 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 BEST4 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 BEST4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing BEST4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with BEST4 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 BEST4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with BEST4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by BEST4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with BEST4 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 BEST4 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 BEST4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at BEST4 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 BEST4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of BEST4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with BEST4 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 BEST4 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of BEST4 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 BEST4 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 BEST4 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 BEST4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving BEST4 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing BEST4 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by BEST4 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by BEST4 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of BEST4 gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of BEST4 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 BEST4 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 BEST4 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 BEST4 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of BEST4 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HMDB Metabolites of Enzymes | interacting metabolites for BEST4 protein from the curated HMDB Metabolites of Enzymes dataset. | |
| HPA Cell Line Gene Expression Profiles | cell lines with high or low expression of BEST4 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 BEST4 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 BEST4 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 BEST4 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| HuBMAP ASCT+B Annotations | cell types associated with BEST4 gene from the HuBMAP ASCT+B dataset. | |
| HuBMAP ASCT+B Augmented with RNA-seq Coexpression | cell types associated with BEST4 gene from the HuBMAP ASCT+B Augmented with RNA-seq Coexpression dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for BEST4 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of BEST4 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 BEST4 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 BEST4 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 BEST4 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain BEST4 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of BEST4 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 BEST4 gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of BEST4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| Reactome Pathways 2014 | pathways involving BEST4 protein from the Reactome Pathways dataset. | |
| Reactome Pathways 2024 | pathways involving BEST4 protein from the Reactome Pathways 2024 dataset. | |
| Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of BEST4 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
| Roadmap Epigenomics Cell and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of BEST4 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at BEST4 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of BEST4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of BEST4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of BEST4 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of BEST4 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of BEST4 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 BEST4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with BEST4 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 BEST4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
