KCTD1 Gene

Name	potassium channel tetramerization domain containing 1
Description	This gene encodes a protein containing a BTB (Broad-complex, tramtrack and bric a brac), also known as a POZ (POxvirus and zinc finger) protein-protein interaction domain. The encoded protein negatively regulates the AP-2 family of transcription factors and the Wnt signaling pathway. A mechanism for the modulation of Wnt signaling has been proposed in which the encoded protein enhances ubiquitination and degradation of the beta-catenin protein. Mutations in this gene have been identified in Scalp-ear-nipple (SEN) syndrome. [provided by RefSeq, May 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KCTD1 is a multifunctional protein whose activity is mediated by its conserved BTB domain, which facilitates protein–protein interactions that are critical for modulating transcriptional and signaling pathways. In the developing ectoderm, KCTD1 acts as a transcriptional repressor by binding to and inhibiting AP‐2 family transcription factors – notably AP‐2α – a function that is essential for proper ectodermal differentiation; mutations that impair this interaction are causative for scalp–ear–nipple syndrome, where protein destabilization and aggregation are observed (for example."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in ectodermal development, KCTD1 also contributes to organ-specific differentiation processes. In the kidney, for instance, it functions as a downstream target of the transcription factor AP‐2β to promote the terminal differentiation of early distal convoluted tubule cells and protect against renal fibrosis by repressing β‐catenin activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, during adipogenesis KCTD1 expression is up‐regulated, and it facilitates differentiation by interacting with and relocating AP‐2α away from the nucleus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, KCTD1 has also been implicated in the regulation of the canonical Wnt signaling pathway. It promotes the phosphorylation‐dependent ubiquitination and subsequent degradation of β‐catenin—a process that requires cooperation with kinases such as CK1 and GSK‐3β and the ubiquitin ligase β‐TrCP—thereby inhibiting downstream Wnt target gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Notably, although many BTB-domain proteins serve as substrate adaptors for Cul3-based ubiquitin ligases, studies have consistently shown that KCTD1 does not exhibit detectable binding to Cul3."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, biophysical studies have provided insights into the structural stability and folding properties of KCTD1. Recombinant expression and circular dichroism analyses underscore the importance of its secondary structure for proper function. Moreover, under conditions of elevated copper ion concentration, KCTD1 acquires increased β‑sheet content and forms aggregation-prone, protease-resistant species that are associated with cell toxicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, KCTD1 functions as a transcriptional repressor—most notably by regulating AP‐2α activity—to influence ectodermal development and differentiation in multiple tissues. Its role in promoting the degradation of β‐catenin further connects it to the modulation of Wnt signaling, which is critical for proper cell fate determination and tissue homeostasis. The precise folding and stability of the KCTD1 protein, governed by its BTB domain and sensitive to metal ion conditions, are essential for its normal biological functions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alexander G Marneros, Anita E Beck, Emily H Turner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in KCTD1 cause scalp-ear-nipple syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2013.03.002"}], "href": "https://doi.org/10.1016/j.ajhg.2013.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23541344"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23541344"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiaofeng Ding, Chang Luo, Jianlin Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The interaction of KCTD1 with transcription factor AP-2alpha inhibits its transactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.22002"}], "href": "https://doi.org/10.1002/jcb.22002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19115315"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19115315"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Giovanni Smaldone, Nicole Balasco, Luciano Pirone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular basis of the scalp-ear-nipple syndrome unraveled by the characterization of disease-causing KCTD1 mutants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-46911-4"}], "href": "https://doi.org/10.1038/s41598-019-46911-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31324836"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31324836"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lingyu Hu, Li Chen, Liu Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KCTD1 mutants in scalp‑ear‑nipple syndrome and AP‑2α P59A in Char syndrome reciprocally abrogate their interactions, but can regulate Wnt/β‑catenin signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2020.11457"}], "href": "https://doi.org/10.3892/mmr.2020.11457"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33000225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33000225"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Alexander G Marneros "}, {"type": "b", "children": [{"type": "t", "text": "AP-2β/KCTD1 Control Distal Nephron Differentiation and Protect against Renal Fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2020.05.026"}], "href": "https://doi.org/10.1016/j.devcel.2020.05.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32553120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32553120"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Luciano Pirone, Giovanni Smaldone, Rosa Spinelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KCTD1: A novel modulator of adipogenesis through the interaction with the transcription factor AP2α."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Biol Lipids (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbalip.2019.08.010"}], "href": "https://doi.org/10.1016/j.bbalip.2019.08.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31465887"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31465887"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xinxin Li, Cheng Chen, Fangmei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KCTD1 suppresses canonical Wnt signaling pathway by enhancing β-catenin degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0094343"}], "href": "https://doi.org/10.1371/journal.pone.0094343"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24736394"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24736394"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Rabia Habib, Muhammad Ansar, Manuel Mattheisen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Novel Locus for Ectodermal Dysplasia of Hair, Nail and Skin Pigmentation Anomalies Maps to Chromosome 18p11.32-p11.31."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0129811"}], "href": "https://doi.org/10.1371/journal.pone.0129811"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26115030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26115030"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Alan X Ji, Anh Chu, Tine Kragh Nielsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural Insights into KCTD Protein Assembly and Cullin3 Recognition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2015.08.019"}], "href": "https://doi.org/10.1016/j.jmb.2015.08.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26334369"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26334369"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Giovanni Smaldone, Luciano Pirone, Nicole Balasco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cullin 3 Recognition Is Not a Universal Property among KCTD Proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0126808"}], "href": "https://doi.org/10.1371/journal.pone.0126808"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25974686"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25974686"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Zhepeng Liu, Feifei Song, Zhi-Li Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bivalent Copper Ions Promote Fibrillar Aggregation of KCTD1 and Induce Cytotoxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep32658"}], "href": "https://doi.org/10.1038/srep32658"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27596723"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27596723"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Fanghua Mei, Jin Xiang, Song Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression, purification, and secondary structure characterization of recombinant KCTD1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (Mosc) (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1134/S0006297912080160"}], "href": "https://doi.org/10.1134/S0006297912080160"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22860917"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22860917"}]}]}]}
Synonyms	SENS, C18ORF5
Proteins	KCTD1_HUMAN
NCBI Gene ID	284252
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KCTD1 has 4,089 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 113 datasets.

Click the + buttons to view associations for KCTD1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KCTD1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KCTD1 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 KCTD1 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 KCTD1 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 KCTD1 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 KCTD1 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 KCTD1 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 KCTD1 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 KCTD1 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 KCTD1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with KCTD1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KCTD1 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 KCTD1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KCTD1 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 KCTD1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with KCTD1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with KCTD1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of KCTD1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KCTD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KCTD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing KCTD1 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 KCTD1 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 KCTD1 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 KCTD1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KCTD1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KCTD1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KCTD1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with KCTD1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of KCTD1 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 KCTD1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving KCTD1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with KCTD1 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 KCTD1 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 KCTD1 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 KCTD1 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 KCTD1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KCTD1 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 KCTD1 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 KCTD1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KCTD1 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 KCTD1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.