CYB561 Gene

HGNC Family	Cytochrome b561 (CYB561)
Name	cytochrome b561
Description	Predicted to enable transmembrane monodehydroascorbate reductase activity. Predicted to be involved in ascorbate homeostasis. Predicted to be located in chromaffin granule membrane. Predicted to be active in lysosomal membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cytochrome b561 (CYB561) proteins are integral transmembrane electron transporters that play key roles in ascorbate recycling and iron homeostasis. For instance, increased CYB561 expression has been observed in senescing human oral keratinocytes, suggesting a potential involvement in cellular aging processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In cancer, studies have demonstrated that a CYB561 family member (CYB561A3) is critical for sustaining intracellular iron balance; its knockout in Burkitt lymphoma cells induces profound iron starvation, lysosomal and mitochondrial damage, and impaired respiration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, pathogenic mutations in CYB561 have been linked to autonomic dysfunction. Patients harboring loss‐of‐function mutations exhibit defective catecholamine biosynthesis with undetectable norepinephrine levels and severe orthostatic hypotension."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Common CYB561 variants have also been associated with blunted vascular responses"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and, through disrupted microRNA binding in its 3′-UTR, with modulation of heart rate and autonomic tone."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the oncologic context, aberrant expression of CYB561 and even a related long noncoding RNA (lnc‑CYB561‑5) have been implicated in tumor progression; high CYB561 levels in breast cancer and overexpression of lnc‑CYB561‑5 in non–small cell lung cancer correlate with aggressive disease and poor prognosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, CYB561 proteins are characterized by a unique “two‐heme, six-transmembrane” structure that enables their function as electron shuttles. These electrons are used to reduce ferric iron to its more soluble ferrous state – a process essential both for nonheme iron absorption and for the proper functioning of dopamine β-hydroxylase in catecholamine synthesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": " Furthermore, a homologous CYB561 protein in the parasitic flatworm Schistosoma japonicum has been shown to reconstitute ferric reductase activity in yeast, reinforcing the role of CYB561 proteins in iron metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted roles of CYB561 proteins in regulating cellular redox balance, iron homeostasis, and catecholamine biosynthesis. Alterations in CYB561 expression or function can contribute to pathologies ranging from cellular senescence and cardiovascular dysregulation to oncogenesis, highlighting its potential as both a biomarker and therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mo K Kang, Ayako Kameta, Ki-Hyuk Shin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Senescence-associated genes in normal human oral keratinocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0014-4827(03)00061-2"}], "href": "https://doi.org/10.1016/s0014-4827(03"}, {"type": "t", "text": "00061-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12837283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12837283"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhonghao Wang, Rui Guo, Stephen J Trudeau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CYB561A3 is the key lysosomal iron reductase required for Burkitt B-cell growth and survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood.2021011079"}], "href": "https://doi.org/10.1182/blood.2021011079"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34232987"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34232987"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Maarten P van den Berg, Rowida Almomani, Italo Biaggioni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "CYB561"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Causing a Novel Orthostatic Hypotension Syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.117.311949"}], "href": "https://doi.org/10.1161/CIRCRESAHA.117.311949"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29343526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29343526"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Cyndya A Shibao, Emily M Garland, Bonnie K Black, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Congenital absence of norepinephrine due to "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "CYB561"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0000000000008734"}], "href": "https://doi.org/10.1212/WNL.0000000000008734"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31822578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31822578"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Maple M Fung, Carie Nguyen, Parag Mehtani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation within adrenergic pathways determines in vivo effects of presynaptic stimulation in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.107.706317"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.107.706317"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18180394"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18180394"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kuixing Zhang, Dekker C Deacon, Fangwen Rao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human heart rate: heritability of resting and stress values in twin pairs, and influence of genetic variation in the adrenergic pathway at a microribonucleic acid (microrna) motif in the 3'-UTR of cytochrome b561 [corrected]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Coll Cardiol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jacc.2013.09.025"}], "href": "https://doi.org/10.1016/j.jacc.2013.09.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24140660"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24140660"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Longfei Li, Zhimin Li, Jingming Qu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel long non-coding RNA CYB561-5 promotes aerobic glycolysis and tumorigenesis by interacting with basigin in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.17057"}], "href": "https://doi.org/10.1111/jcmm.17057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35064752"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35064752"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xiaochen Yang, Yangjing Zhao, Qixiang Shao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytochrome b561 Serves as a Potential Prognostic Biomarker and Target for Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Gen Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/IJGM.S338878"}], "href": "https://doi.org/10.2147/IJGM.S338878"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35002301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35002301"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xiaofeng Zhou, GuoShuang Shen, Dengfeng Ren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and clinical prognostic value of CYB561 in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-022-03928-z"}], "href": "https://doi.org/10.1007/s00432-022-03928-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35486183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35486183"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Alajos Bérczi, László Zimányi "}, {"type": "b", "children": [{"type": "t", "text": "The trans-membrane cytochrome b561 proteins: structural information and biological function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Protein Pept Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2174/1389203715666140828100351"}], "href": "https://doi.org/10.2174/1389203715666140828100351"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25163754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25163754"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Cristiana Picco, Joachim Scholz-Starke, Alessia Naso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "How are cytochrome b561 electron currents controlled by membrane voltage and substrate availability?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Antioxid Redox Signal (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ars.2013.5809"}], "href": "https://doi.org/10.1089/ars.2013.5809"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24410448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24410448"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Han Asard, Raffaella Barbaro, Paolo Trost, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytochromes b561: ascorbate-mediated trans-membrane electron transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Antioxid Redox Signal (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ars.2012.5065"}], "href": "https://doi.org/10.1089/ars.2012.5065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23249217"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23249217"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Darius J R Lane, Dong-Hun Bae, Angelica M Merlot, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Duodenal cytochrome b (DCYTB) in iron metabolism: an update on function and regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nutrients (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/nu7042274"}], "href": "https://doi.org/10.3390/nu7042274"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25835049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25835049"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Amber Glanfield, Donald P McManus, Danielle J Smyth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A cytochrome b561 with ferric reductase activity from the parasitic blood fluke, Schistosoma japonicum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Negl Trop Dis (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pntd.0000884"}], "href": "https://doi.org/10.1371/journal.pntd.0000884"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21103361"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21103361"}]}]}]}
Synonyms	CYB561A1, FRRS2
Proteins	CY561_HUMAN
NCBI Gene ID	1534
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CYB561 has 7,179 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 114 datasets.

Click the + buttons to view associations for CYB561 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CYB561 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 CYB561 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 CYB561 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 CYB561 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 CYB561 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 CYB561 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 CYB561 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 CYB561 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 CYB561 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 CYB561 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 CYB561 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 CYB561 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 CYB561 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CYB561 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CYB561 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 CYB561 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CYB561 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 CYB561 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CYB561 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CYB561 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CYB561 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CYB561 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 CYB561 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 CYB561 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CYB561 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CYB561 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CYB561 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CYB561 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 CYB561 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 CYB561 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 CYB561 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 CYB561 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 CYB561 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CYB561 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 CYB561 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 CYB561 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CYB561 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 CYB561 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CYB561 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CYB561 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CYB561 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.