NCOA4 Gene

Name	nuclear receptor coactivator 4
Description	This gene encodes an androgen receptor coactivator. The encoded protein interacts with the androgen receptor in a ligand-dependent manner to enhance its transcriptional activity. Chromosomal translocations between this gene and the ret tyrosine kinase gene, also located on chromosome 10, have been associated with papillary thyroid carcinoma. Alternatively spliced transcript variants have been described. Pseudogenes are present on chromosomes 4, 5, 10, and 14. [provided by RefSeq, Feb 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNCOA4 is a selective autophagic cargo receptor that directly binds ferritin—particularly its heavy chain—to mediate the lysosomal degradation of this iron‐storage complex in a process known as ferritinophagy. Biochemical studies using defined NCOA4 fragments have revealed its high‐affinity interaction with ferritin, demonstrating that this binding is critical for releasing iron under conditions of iron depletion or cellular stress. In addition, NCOA4 levels are dynamically regulated by iron availability and ubiquitin–proteasome–mediated degradation, thereby controlling ferritin turnover and influencing cell susceptibility to ferroptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of NCOA4‐mediated ferritinophagy has emerged as an important mechanism implicated in several diseases. In cancers such as clear cell renal cell carcinoma and prostate cancer, altered NCOA4 expression influences intracellular iron homeostasis and ferroptosis sensitivity, potentially impacting tumor progression. Moreover, in certain salivary gland tumors, gene rearrangements—such as the NCOA4‐RET fusion—underscore the role of NCOA4 as an oncogenic partner, highlighting its involvement in aberrant signaling pathways that drive neoplastic transformation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its central function in iron metabolism, NCOA4 has been linked to the regulation of ferroptosis in non‐cancerous pathologies. For example, in osteoarthritis, upregulation of NCOA4—as induced by JNK–JUN signaling—promotes ferritin degradation, leading to excess intracellular labile iron, oxidative stress, and chondrocyte ferroptosis, thereby contributing to extracellular matrix degradation and disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Joseph D Mancias, Xiaoxu Wang, Steven P Gygi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature13148"}], "href": "https://doi.org/10.1038/nature13148"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24695223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24695223"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "William E Dowdle, Beat Nyfeler, Jane Nagel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3053"}], "href": "https://doi.org/10.1038/ncb3053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25327288"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25327288"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Joseph D Mancias, Laura Pontano Vaites, Sahar Nissim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.10308"}], "href": "https://doi.org/10.7554/eLife.10308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26436293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26436293"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Wen Hou, Yangchun Xie, Xinxin Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autophagy promotes ferroptosis by degradation of ferritin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2016.1187366"}], "href": "https://doi.org/10.1080/15548627.2016.1187366"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27245739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27245739"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Magdalena Gryzik, Ayush Srivastava, Giovanna Longhi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and characterization of the ferritin binding domain of Nuclear Receptor Coactivator-4 (NCOA4)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Gen Subj (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagen.2017.07.015"}], "href": "https://doi.org/10.1016/j.bbagen.2017.07.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28754384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28754384"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mark M Pomerantz, Yashaswi Shrestha, Richard J Flavin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of the 10q11 cancer risk locus implicates MSMB and NCOA4 in human prostate tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1001204"}], "href": "https://doi.org/10.1371/journal.pgen.1001204"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21085629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21085629"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Alena Skálová, Nikola Ptáková, Thalita Santana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NCOA4-RET and TRIM27-RET Are Characteristic Gene Fusions in Salivary Intraductal Carcinoma, Including Invasive and Metastatic Tumors: Is \"Intraductal\" Correct?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0000000000001301"}], "href": "https://doi.org/10.1097/PAS.0000000000001301"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31162284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31162284"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yanhua Mou, Jinchun Wu, Yao Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Low expression of ferritinophagy-related NCOA4 gene in relation to unfavorable outcome and defective immune cells infiltration in clear cell renal carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12885-020-07726-z"}], "href": "https://doi.org/10.1186/s12885-020-07726-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33402128"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33402128"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yulin Zhang, Yang Kong, Yuan Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of COPZ1 induces NCOA4 mediated autophagy and ferroptosis in glioblastoma cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-020-01622-3"}], "href": "https://doi.org/10.1038/s41388-020-01622-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33420375"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33420375"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Naiara Santana-Codina, Ajami Gikandi, Joseph D Mancias "}, {"type": "b", "children": [{"type": "t", "text": "The Role of NCOA4-Mediated Ferritinophagy in Ferroptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Exp Med Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-3-030-62026-4_4"}], "href": "https://doi.org/10.1007/978-3-030-62026-4_4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34370287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34370287"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Lanying Song, Wensheng Yan, Xinbin Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myocardial smad4 is essential for cardiogenesis in mouse embryos."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.107.155630"}], "href": "https://doi.org/10.1161/CIRCRESAHA.107.155630"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17585069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17585069"}]}]}]}
Synonyms	ARA70, ELE1, PTC3, RFG
Proteins	NCOA4_HUMAN
NCBI Gene ID	8031
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NCOA4 has 7,407 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 123 datasets.

Click the + buttons to view associations for NCOA4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NCOA4 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by NCOA4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NCOA4 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 NCOA4 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 NCOA4 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 NCOA4 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 NCOA4 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 NCOA4 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 NCOA4 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 NCOA4 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 NCOA4 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 NCOA4 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 NCOA4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with NCOA4 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NCOA4 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 NCOA4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NCOA4 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 NCOA4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing NCOA4 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 NCOA4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NCOA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NCOA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing NCOA4 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 NCOA4 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 NCOA4 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 NCOA4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NCOA4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NCOA4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NCOA4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NCOA4 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 NCOA4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving NCOA4 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving NCOA4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NCOA4 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 NCOA4 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 NCOA4 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 NCOA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NCOA4 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 NCOA4 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 NCOA4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NCOA4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.