KCTD21 Gene

Name potassium channel tetramerization domain containing 21
Description Enables cullin family protein binding activity; histone deacetylase binding activity; and identical protein binding activity. Involved in negative regulation of smoothened signaling pathway and ubiquitin-dependent protein catabolic process. [provided by Alliance of Genome Resources, Mar 2025]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KCASH2, also known as KCTD21, is a member of a novel family of BTB/POZ‐domain proteins that function as endogenous inhibitors of the Hedgehog (Hh) signaling pathway. This protein acts as a tumor suppressor by promoting the ubiquitination‐dependent degradation of histone deacetylase 1 (HDAC1), a key event that leads to hyperacetylation and consequent inhibition of Gli transcription factors—the main effectors of Hh signaling. Consequently, KCASH2 dampens Hh pathway activity and reduces Hh‐mediated cell proliferation, a mechanism particularly relevant in the context of medulloblastoma where reduced KCASH2 expression contributes to sustained oncogenic Hh activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Regulation of KCASH2 expression is complex, involving key transcriptional regulators. For instance, transcription factor Sp1 has been shown to activate the TATA‐less proximal promoter of KCASH2, whereas p53 exerts a negative regulatory effect. This fine‐tuned balance between Sp1 and p53 contributes to the overall level of KCASH2 and, by extension, to the suppression of aberrant Hh signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, interactions with other KCTD family members, such as the direct binding of KCTD15 to KCASH2 via its BTB/POZ domain, have been demonstrated to further stabilize KCASH2, thereby reinforcing its inhibitory role on the Hh pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its critical function in modulating Hh-driven tumorigenesis, alterations in KCTD21 have also been implicated in neuropsychiatric disorders, including schizophrenia. Genetic studies have uncovered rare variants in KCTD21 that may contribute to the heterogeneous genetic architecture of neurodevelopmental conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Together, these findings highlight KCTD21/KCASH2 as a pivotal regulator of both oncogenic and neurodevelopmental pathways, suggesting its potential as a prognostic marker and therapeutic target in medulloblastoma and possibly other disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Enrico De Smaele, Lucia Di Marcotullio, Marta Moretti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of KCASH2 and KCASH3, 2 novel Cullin3 adaptors suppressing histone deacetylase and Hedgehog activity in medulloblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1593/neo.101630"}], "href": "https://doi.org/10.1593/neo.101630"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21472142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21472142"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eleonora Spiombi, Annapaola Angrisani, Simone Fonte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KCTD15 inhibits the Hedgehog pathway in Medulloblastoma cells by increasing protein levels of the oncosuppressor KCASH2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogenesis (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41389-019-0175-6"}], "href": "https://doi.org/10.1038/s41389-019-0175-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31685809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31685809"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Annapaola Angrisani, Annamaria Di Fiore, Claudia Augusta Di Trani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific Protein 1 and p53 Interplay Modulates the Expression of the KCTD-Containing Cullin3 Adaptor Suppressor of Hedgehog 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Cell Dev Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fcell.2021.638508"}], "href": "https://doi.org/10.3389/fcell.2021.638508"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33898425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33898425"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Bashayer Al-Mubarak, Mohamed Abouelhoda, Aisha Omar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-06033-1"}], "href": "https://doi.org/10.1038/s41598-017-06033-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28720891"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28720891"}]}]}]}
Synonyms KCASH2
Proteins KCD21_HUMAN
NCBI Gene ID 283219
API
Download Associations
Predicted Functions View KCTD21's ARCHS4 Predicted Functions.
Co-expressed Genes View KCTD21's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View KCTD21's ARCHS4 Predicted Functions.

Functional Associations

KCTD21 has 4,246 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 85 datasets.

Click the + buttons to view associations for KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of KCTD21 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 KCTD21 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CCLE Cell Line Proteomics Cell lines associated with KCTD21 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 KCTD21 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of KCTD21 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 KCTD21 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 KCTD21 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
CM4AI U2OS Cell Map Protein Localization Assemblies assemblies containing KCTD21 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores cellular components containing KCTD21 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 cellular components containing KCTD21 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with KCTD21 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 KCTD21 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 KCTD21 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with KCTD21 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Disease Associations diseases associated with KCTD21 gene/protein from the curated CTD Gene-Disease Associations dataset.
DeepCoverMOA Drug Mechanisms of Action small molecule perturbations with high or low expression of KCTD21 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 KCTD21 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Curated Gene-Disease Association Evidence Scores 2025 diseases involving KCTD21 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with KCTD21 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 KCTD21 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 KCTD21 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of KCTD21 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 KCTD21 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with KCTD21 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 KCTD21 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving KCTD21 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving KCTD21 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving KCTD21 gene from the curated GO Biological Process Annotations2025 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by KCTD21 gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by KCTD21 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx eQTL 2025 SNPs regulating expression of KCTD21 gene from the GTEx eQTL 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for KCTD21 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 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 KCTD21 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain KCTD21 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of KCTD21 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 KCTD21 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
NURSA Protein Complexes protein complexs containing KCTD21 protein recovered by IP-MS from the NURSA Protein Complexes dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for KCTD21 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of KCTD21 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 KCTD21 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
Roadmap Epigenomics Cell and Tissue Gene Expression Profiles cell types and tissues with high or low expression of KCTD21 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 KCTD21 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of KCTD21 gene from the Rummagene Transcription Factor Associations 2026 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of KCTD21 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of KCTD21 gene from the RummaGEO Gene Perturbation Signatures dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of KCTD21 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of KCTD21 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 KCTD21 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 KCTD21 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of KCTD21 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of KCTD21 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with KCTD21 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 KCTD21 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.