| HGNC Family | BTB (POZ) domain containing (BTBD) |
| Name | kelch repeat and BTB (POZ) domain containing 4 |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KBTBD4 is a member of the BTB‐Kelch family that functions as a substrate adaptor within CULLIN3‐RING E3 ubiquitin ligase complexes, thereby dictating target specificity for protein ubiquitylation. In several studies of medulloblastoma, recurrent in‐frame insertion mutations in KBTBD4 have been identified as primary driver events, particularly within non‐WNT/non‐SHH subgroups—including pediatric Group 3/4 and adult medulloblastomas—where mutant KBTBD4 gains the novel capacity to recruit and ubiquitinate the REST corepressor (CoREST), leading to its degradation. This aberrant ubiquitylation alters chromatin accessibility and shifts transcriptional programs toward a stem‐like, oncogenic state."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, studies in hematopoietic stem cells have demonstrated that KBTBD4 directs the substrate specificity of a CRL3 complex in response to the self‐renewal agonist UM171, implicating its role in modulating CoREST complex function and linking ubiquitin ligase activity to the regulation of stem cell self‐renewal."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, KBTBD4 insertion mutations have also been identified in pineal parenchymal tumors, where they serve as potential diagnostic markers for tumors of intermediate differentiation (PPTID) and help define distinct molecular subgroups."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, these findings position KBTBD4 as both a critical regulator of protein degradation via ubiquitination and a novel oncogenic driver through its impact on epigenetic reprogramming, highlighting its potential as a target for therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhuoyao Chen, Rafael M Ioris, Stacey Richardson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disease-associated KBTBD4 mutations in medulloblastoma elicit neomorphic ubiquitylation activity to promote CoREST degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41418-022-00983-4"}], "href": "https://doi.org/10.1038/s41418-022-00983-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35379950"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35379950"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gabriel Chun-Hei Wong, Kay Ka-Wai Li, Wei-Wei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and mutational profiles of adult medulloblastoma groups."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40478-020-01066-6"}], "href": "https://doi.org/10.1186/s40478-020-01066-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33172502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33172502"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Paul A Northcott, Ivo Buchhalter, A Sorana Morrissy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The whole-genome landscape of medulloblastoma subtypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature22973"}], "href": "https://doi.org/10.1038/nature22973"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28726821"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28726821"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jalila Chagraoui, Simon Girard, Jean-Francois Spinella, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UM171 Preserves Epigenetic Marks that Are Reduced in Ex Vivo Culture of Human HSCs via Potentiation of the CLR3-KBTBD4 Complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stem Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stem.2020.12.002"}], "href": "https://doi.org/10.1016/j.stem.2020.12.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33417871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33417871"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Anthony P Y Liu, Bryan K Li, Elke Pfaff, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-021-02284-5"}], "href": "https://doi.org/10.1007/s00401-021-02284-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33619588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33619588"}]}]}]}
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| Synonyms | BKLHD4, HSPC252 |
| Proteins | KBTB4_HUMAN |
| NCBI Gene ID | 55709 |
| 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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KBTBD4 has 5,399 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 83 datasets.
Click the + buttons to view associations for KBTBD4 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 KBTBD4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles | tissues with high or low expression of KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| BioGPS Mouse Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of KBTBD4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
| Carcinogenome Chemical Perturbation Carcinogenicity Signatures | small molecule perturbations changing expression of KBTBD4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of KBTBD4 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 KBTBD4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| CCLE Cell Line Proteomics | Cell lines associated with KBTBD4 protein from the CCLE Cell Line Proteomics dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of KBTBD4 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of KBTBD4 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 KBTBD4 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 KBTBD4 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of KBTBD4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| COMPARTMENTS Experimental Protein Localization Evidence Scores | cellular components containing KBTBD4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with KBTBD4 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 KBTBD4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with KBTBD4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| CTD Gene-Disease Associations | diseases associated with KBTBD4 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DeepCoverMOA Drug Mechanisms of Action | small molecule perturbations with high or low expression of KBTBD4 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with KBTBD4 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 KBTBD4 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 KBTBD4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of KBTBD4 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 KBTBD4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GDSC Cell Line Gene Expression Profiles | cell lines with high or low expression of KBTBD4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing KBTBD4 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with KBTBD4 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for KBTBD4 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of KBTBD4 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 KBTBD4 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 KBTBD4 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 KBTBD4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles | cell lines with high or low expression of KBTBD4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles | cell lines with KBTBD4 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of KBTBD4 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 KBTBD4 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
| LINCS L1000 CMAP CRISPR Knockout Consensus Signatures | gene perturbations changing expression of KBTBD4 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset. | |
| LOCATE Curated Protein Localization Annotations | cellular components containing KBTBD4 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 KBTBD4 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MiRTarBase microRNA Targets | microRNAs targeting KBTBD4 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of KBTBD4 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 KBTBD4 gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
| NURSA Protein Complexes | protein complexs containing KBTBD4 protein recovered by IP-MS from the NURSA Protein Complexes dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for KBTBD4 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of KBTBD4 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 KBTBD4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of KBTBD4 gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset. | |
| Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of KBTBD4 gene from the Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures dataset. | |
| Roadmap Epigenomics Cell and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of KBTBD4 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 KBTBD4 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of KBTBD4 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of KBTBD4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of KBTBD4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of KBTBD4 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of KBTBD4 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 KBTBD4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores | tissues with high expression of KBTBD4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of KBTBD4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with KBTBD4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
