RNF220 Gene

HGNC Family	Zinc fingers
Name	ring finger protein 220
Description	Enables beta-catenin binding activity. Involved in positive regulation of canonical Wnt signaling pathway. Acts upstream of or within positive regulation of DNA-binding transcription factor activity and protein monoubiquitination. Located in nuclear lamina. Part of protein-containing complex. Implicated in hypomyelinating leukodystrophy 23. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNF220 is a RING domain E3 ubiquitin ligase with multifaceted functions in cellular signal regulation. In the context of canonical Wnt/β-catenin signaling, RNF220 physically interacts with β-catenin and partners with the deubiquitinating enzyme USP7 to remove ubiquitin modifications from β-catenin. This action stabilizes β-catenin and enhances Wnt signaling through a positive feedback loop, while its own stability is tightly controlled by Gsk3β."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn reproductive biology, a homozygous mutation in RNF220 has been linked to abnormal chromatin condensation in spermatozoa, resulting in small-headed sperm. Here, RNF220 normally promotes the ubiquitination and subsequent proteasomal degradation of the chromatin-associated protein SIN3B. Disruption of this function leads to excessive chromatin condensation during spermatogenesis and infertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn acute myeloid leukemia (AML), RNF220 is overexpressed in leukemic bone marrow cells compared with normal hematopoietic stem cells. This overexpression promotes cell cycle progression by stabilizing Cyclin D1, a process that is mediated by increased USP22 expression, thereby contributing to enhanced proliferation of AML cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRNF220 also emerges as a critical regulator in the nervous system. Missense mutations in RNF220 have been identified in patients with a novel form of leukodystrophy characterized by ataxia and sensorineural deafness. The impaired interaction of mutant RNF220 with lamin B1 disrupts nuclear lamina integrity, leading to nuclear abnormalities reminiscent of laminopathies and contributing to neurodegeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn colon cancer, RNF220 is upregulated in both patient samples and cell models, where it facilitates tumor progression by promoting cell proliferation, migration, invasion, and stemness. This oncogenic effect occurs via modulation of the USP22–BMI1 axis, underscoring the role of RNF220 in colorectal cancer pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRNF220 is also central to the regulation of Sonic hedgehog (Shh) signaling during cerebellar development and medulloblastoma progression. It is required for sustained high Shh pathway activation in cerebellar granule neuron progenitors, a function that depends on its stabilization by factors such as ZC4H2 and the E3 ligase RLIM. Furthermore, RNF220 protein levels are modulated by additional E3 ubiquitin ligases, Smurf1 and Smurf2, which target it for degradation, thereby fine-tuning Shh signaling in medulloblastoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pengcheng Ma, Xiangcai Yang, Qinghua Kong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ubiquitin ligase RNF220 enhances canonical Wnt signaling through USP7-mediated deubiquitination of β-catenin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00731-14"}], "href": "https://doi.org/10.1128/MCB.00731-14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25266658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25266658"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiaohui Jiang, Xiang Wang, Xueguang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A homozygous RNF220 mutation leads to male infertility with small-headed sperm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2018.11.074"}], "href": "https://doi.org/10.1016/j.gene.2018.11.074"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30500349"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30500349"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuming Pan, Na An, Xiaopeng Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNF220 promotes the proliferation of leukaemic cells and reduces the degradation of the Cyclin D1 protein through USP22."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Cells Mol Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bcmd.2020.102490"}], "href": "https://doi.org/10.1016/j.bcmd.2020.102490"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32896826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32896826"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Antonella Sferra, Paola Fortugno, Marialetizia Motta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic mutations in RNF220 cause laminopathies featuring leukodystrophy, ataxia and deafness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awab185"}], "href": "https://doi.org/10.1093/brain/awab185"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33964137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33964137"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jianwen Yan, Min Tan, Lin Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ring finger 220 promotes the stemness and progression of colon cancer cells via Ubiquitin specific peptidase 22-BMI1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.2003664"}], "href": "https://doi.org/10.1080/21655979.2021.2003664"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34753387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34753387"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yuwei Li, Chencheng Yang, Huishan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sequential stabilization of RNF220 by RLIM and ZC4H2 during cerebellum development and Shh-group medulloblastoma progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Biol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jmcb/mjab082"}], "href": "https://doi.org/10.1093/jmcb/mjab082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35040952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35040952"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yuwei Li, Huishan Wang, Bin Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Smurf1 and Smurf2 mediated polyubiquitination and degradation of RNF220 suppresses Shh-group medulloblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-023-06025-2"}], "href": "https://doi.org/10.1038/s41419-023-06025-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37537194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37537194"}]}]}]}
Synonyms	C1ORF164
Proteins	RN220_HUMAN
NCBI Gene ID	55182
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RNF220 has 5,668 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 126 datasets.

Click the + buttons to view associations for RNF220 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RNF220 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 RNF220 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 RNF220 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 RNF220 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 RNF220 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 RNF220 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 RNF220 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 RNF220 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 RNF220 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 RNF220 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 RNF220 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RNF220 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 RNF220 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RNF220 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RNF220 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 RNF220 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RNF220 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 RNF220 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 RNF220 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of RNF220 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing RNF220 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 RNF220 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RNF220 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RNF220 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RNF220 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 RNF220 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 RNF220 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 RNF220 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 RNF220 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RNF220 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RNF220 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RNF220 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with RNF220 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 RNF220 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 RNF220 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving RNF220 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with RNF220 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 RNF220 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RNF220 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 RNF220 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 RNF220 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.