DCAF8 Gene

HGNC Family	WD repeat domain containing (WDR), DDB1 and CUL4 associated factors (DCAF)
Name	DDB1 and CUL4 associated factor 8
Description	This gene encodes a WD repeat-containing protein that interacts with the Cul4-Ddb1 E3 ligase macromolecular complex. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DCAF8 is a WD40‐repeat–containing protein that functions as a substrate receptor for Cullin–RING E3 ubiquitin ligase complexes (CRL4), thereby guiding the ubiquitination and degradation of specific protein targets. In the nervous system, a point mutation within the DCAF8 WD40 region (p.R317C) was shown to impair its association with DDB1, leading to defects in neurofilament degradation and contributing to a form of axonal hereditary motor and sensory neuropathy with infrequent giant axons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the reproductive system, knockout studies in mice demonstrated that loss of DCAF8 results in impaired spermatogenesis characterized by reduced sperm motility and morphological abnormalities, underscoring its critical role in male fertility."}, {"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 roles in neuronal and reproductive cells, DCAF8 also participates in chromatin regulation. In hepatocytes, DCAF8 directs a CRL4 complex to polyubiquitinate histone H3 at lysine 79, thereby modulating H3K9 methylation and repressing the expression of fetal and cell‐cycle genes; inactivation of DCAF8 in this context reactivates these genes and drives cell senescence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, unbiased screening approaches have identified the CRL4B–DDB1–DCAF8 complex as a novel E3 ligase for Cdc25A, illustrating its broader importance in regulating cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In muscle tissue, DCAF8 has been found to interact with the muscle‐specific ubiquitin ligase MuRF1. The MuRF1–DCAF8 partnership is important for the CRL4A‐dependent degradation of myosin heavy chain proteins, and the downregulation of either component can impede muscle atrophy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, recent studies have extended the repertoire of DCAF8 substrates by implicating it in the stability control of chromatin remodelers such as LSH, as well as in the regulation of pro‐inflammatory mediators like HMGB1 in sepsis‐induced myocardial dysfunction—further emphasizing its multifaceted role in cellular protein homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings reveal that DCAF8 serves as an essential adapter that links specific substrates to the CRL4 E3 ubiquitin ligase machinery. Through its regulation of protein degradation in diverse contexts—including neuronal integrity, spermatogenesis, cell cycle control, muscle homeostasis, chromatin remodeling, and inflammatory responses—DCAF8 emerges as a pivotal regulator whose dysfunction may underlie multiple disease processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christopher J Klein, Yanhong Wu, Peter Vogel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin ligase defect by DCAF8 mutation causes HMSN2 with giant axons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0000000000000206"}], "href": "https://doi.org/10.1212/WNL.0000000000000206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24500646"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24500646"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiuli Zhang, Zhizhou Xia, Xingyu Lv, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DDB1- and CUL4-associated factor 8 plays a critical role in spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11684-021-0851-8"}], "href": "https://doi.org/10.1007/s11684-021-0851-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33855678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33855678"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Gaofeng Li, Tong Ji, Jiang Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRL4"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "DCAF8"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " Ubiquitin Ligase Targets Histone H3K79 and Promotes H3K9 Methylation in the Liver."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2017.01.039"}], "href": "https://doi.org/10.1016/j.celrep.2017.01.039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28178526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28178526"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yuanzhong Wu, Liwen Zhou, Xin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-scale CRISPR-Cas9 screening method for protein stability reveals novel regulators of Cdc25A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Discov (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/celldisc.2016.14"}], "href": "https://doi.org/10.1038/celldisc.2016.14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27462461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27462461"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Marcel Nowak, Benjamin Suenkel, Pablo Porras, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DCAF8, a novel MuRF1 interaction partner, promotes muscle atrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.233395"}], "href": "https://doi.org/10.1242/jcs.233395"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31391242"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31391242"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Daoyuan Huang, Qian Li, Xinpei Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRL4"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "DCAF8"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " dependent opposing stability control over the chromatin remodeler LSH orchestrates epigenetic dynamics in ferroptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41418-020-00689-5"}], "href": "https://doi.org/10.1038/s41418-020-00689-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33288900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33288900"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qingyun Peng, Huifen Xu, Mingbing Xiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The small molecule PSSM0332 disassociates the CRL4A"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "DCAF8"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " E3 ligase complex to decrease the ubiquitination of NcoR1 and inhibit the inflammatory response in a mouse sepsis-induced myocardial dysfunction model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.50186"}], "href": "https://doi.org/10.7150/ijbs.50186"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33061810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33061810"}]}]}]}
Synonyms	GAN2, WDR42A, H326
Proteins	DCAF8_HUMAN
NCBI Gene ID	50717
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DCAF8 has 6,090 functional associations with biological entities spanning 9 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, sequence feature) extracted from 112 datasets.

Click the + buttons to view associations for DCAF8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DCAF8 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 DCAF8 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 DCAF8 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 DCAF8 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 DCAF8 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 DCAF8 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 DCAF8 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 DCAF8 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 DCAF8 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 DCAF8 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 DCAF8 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DCAF8 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 DCAF8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DCAF8 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 DCAF8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DCAF8 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 DCAF8 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 DCAF8 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with DCAF8 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing DCAF8 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of DCAF8 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DCAF8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DCAF8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DCAF8 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 DCAF8 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 DCAF8 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DCAF8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DCAF8 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DCAF8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by DCAF8 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving DCAF8 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving DCAF8 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DCAF8 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 DCAF8 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 DCAF8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DCAF8 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 DCAF8 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 DCAF8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DCAF8 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 DCAF8 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 DCAF8 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.