SPOP Gene

HGNC Family	BTB (POZ) domain containing (BTBD)
Name	speckle-type POZ protein
Description	This gene encodes a protein that may modulate the transcriptional repression activities of death-associated protein 6 (DAXX), which interacts with histone deacetylase, core histones, and other histone-associated proteins. In mouse, the encoded protein binds to the putative leucine zipper domain of macroH2A1.2, a variant H2A histone that is enriched on inactivated X chromosomes. The BTB/POZ domain of this protein has been shown in other proteins to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPOP is a versatile adaptor protein for the CUL3‐based E3 ubiquitin ligase complex that mediates the selective recruitment of substrates for ubiquitination and subsequent proteasomal degradation. Structural and biochemical studies have revealed that SPOP contains an N‐terminal MATH domain for substrate recognition and a BTB domain that drives dimerization and even higher‐order oligomerization—features that underlie its capacity to engage diverse targets and to assemble into nuclear membraneless compartments via phase separation. These molecular properties enable SPOP to coordinate processes as varied as X inactivation and regulation of key transcriptional and signaling proteins."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThrough its ability to recognize specific degron motifs in substrate proteins, SPOP regulates the stability of multiple factors that control cell proliferation, apoptosis, and transcription. It targets key regulators – such as the androgen receptor, ERG, c‐MYC, SRC‐3, BET family proteins, and mediators like Daxx and p62 – whose appropriate turnover is essential for maintaining cellular homeostasis and antitumor barrier functions. In several cancers, including prostate, endometrial and other solid tumors, cancer‐associated SPOP mutations disrupt substrate binding and ubiquitination. This defect results in the accumulation of oncogenic proteins, altered immune checkpoint protein (PD‐L1) levels, and deregulated signaling pathways that contribute to genomic instability, epithelial–mesenchymal transition, and metabolic reprogramming."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, the function of SPOP is highly context dependent across different cancer types. In prostate cancer, for instance, mutation of SPOP not only impairs the degradation of several oncogenic drivers – but also correlates with distinct clinical features and differential responses to targeted therapies – while in Ewing sarcoma, efficient SPOP‐mediated ubiquitination of fusion oncoproteins like EWS–FLI1 has emerged as a promising therapeutic angle. SPOP also influences metabolic pathways and stress responses by regulating substrates such as Cyclin E1, Cdc20, ILF3, and ASCT2, as well as modulating autophagy through p62 ubiquitination. In renal, lung, colorectal and breast cancers, altered expression or promoter methylation of SPOP further underlines its biomarker potential and its role in driving epithelial–mesenchymal transition and metabolic reprogramming."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "30", "end_ref": "40"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Inmaculada Hernández-Muñoz, Anders H Lund, Petra van der Stoop, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0408918102"}], "href": "https://doi.org/10.1073/pnas.0408918102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15897469"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15897469"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jeong Eun Kwon, Muhnho La, Kyu Hee Oh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M600204200"}], "href": "https://doi.org/10.1074/jbc.M600204200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16524876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16524876"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Matthew W Bunce, Igor V Boronenkov, Richard A Anderson "}, {"type": "b", "children": [{"type": "t", "text": "Coordinated activation of the nuclear ubiquitin ligase Cul3-SPOP by the generation of phosphatidylinositol 5-phosphate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M710222200"}], "href": "https://doi.org/10.1074/jbc.M710222200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18218622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18218622"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jiang Liu, Murad Ghanim, Lei Xue, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Higher-order oligomerization promotes localization of SPOP to liquid nuclear speckles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201593169"}], "href": "https://doi.org/10.15252/embj.201593169"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27220849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27220849"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Min S Kim, Eun M Je, Ji E Oh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutational and expressional analyses of SPOP, a candidate tumor suppressor gene, in prostate, gastric and colorectal cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "APMIS (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/apm.12030"}], "href": "https://doi.org/10.1111/apm.12030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23216165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23216165"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Chuandong Geng, Bin He, Limei Xu, et al. 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Ubiquitylome analysis identifies dysregulation of effector substrates in SPOP-mutant prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1250255"}], "href": "https://doi.org/10.1126/science.1250255"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25278611"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25278611"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Wenjian Gan, Xiangpeng Dai, Andrea Lunardi, et al. 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Synonyms	TEF2, BTBD32
Proteins	SPOP_HUMAN
NCBI Gene ID	8405
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SPOP has 7,283 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 125 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

SPOP 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 SPOP 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 SPOP 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 SPOP 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 SPOP 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 SPOP 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 SPOP 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 SPOP 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 SPOP 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 SPOP 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 SPOP gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SPOP 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 SPOP gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SPOP protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SPOP 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 SPOP gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SPOP 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 SPOP gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SPOP gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SPOP 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 SPOP gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SPOP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SPOP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SPOP 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 SPOP protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing SPOP protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SPOP gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SPOP gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with SPOP gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SPOP 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 SPOP 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 SPOP 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 SPOP 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 SPOP 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 SPOP gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SPOP 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 SPOP 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 SPOP gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SPOP 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 SPOP from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SPOP gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.