CITED2 Gene

Name	Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2
Description	The protein encoded by this gene inhibits transactivation of HIF1A-induced genes by competing with binding of hypoxia-inducible factor 1-alpha to p300-CH1. Mutations in this gene are a cause of cardiac septal defects. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CITED2 is a multifunctional transcriptional modulator that exerts context‐dependent effects by interacting with the transcriptional coactivators CBP/p300 and various DNA‐binding proteins. In hypoxic conditions, CITED2 is induced (in part via FOXO3a activation) to function as a negative feedback regulator of hypoxia‐inducible factor–1α (HIF‑1α). By binding the TAZ1 domain of CBP/p300 through its conserved LP(E/Q)L motif, CITED2 displaces HIF‑1α from its coactivator, thereby rapidly attenuating HIF‑1–mediated transcription and reducing the induction of proapoptotic target genes (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in hypoxic regulation, CITED2 is essential for proper embryonic development. Loss or mutation of CITED2 in mouse models leads to a spectrum of developmental abnormalities including cardiac malformations, neural tube defects, abnormal left–right axis patterning, and placental insufficiency."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": " In humans, mutations that compromise CITED2 function have been linked to congenital heart disease, underscoring its role in the orchestration of cardiac gene networks through cooperative interactions with factors such as TFAP2."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, CITED2 collaborates with nuclear receptors such as PPARα to influence metabolic gene expression, and it modulates transforming growth factor–β (TGF‑β) signaling by physically interacting with Smad proteins and p300 to enhance the transcription of downstream effectors such as matrix metalloproteinase‑9."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Moreover, by regulating the expression of polycomb-group genes, CITED2 helps maintain normal cell proliferation and prevent premature cellular senescence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies reveal that CITED2 plays a central role in integrating environmental signals with transcriptional responses that are critical for cell survival, organogenesis, and tissue homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rebecca B Berlow, H Jane Dyson, Peter E Wright "}, {"type": "b", "children": [{"type": "t", "text": "Hypersensitive termination of the hypoxic response by a disordered protein switch."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature21705"}], "href": "https://doi.org/10.1038/nature21705"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28273070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28273070"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Roberto N De Guzman, Maria A Martinez-Yamout, H Jane Dyson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of the TAZ1 domain of the CREB-binding protein with the activation domain of CITED2: regulation by competition between intrinsically unstructured ligands for non-identical binding sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M310348200"}], "href": "https://doi.org/10.1074/jbc.M310348200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14594809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14594809"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Walbert J Bakker, Isaac S Harris, Tak W Mak "}, {"type": "b", "children": [{"type": "t", "text": "FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2007.10.035"}], "href": "https://doi.org/10.1016/j.molcel.2007.10.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18158893"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18158893"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhan Yin, Jennifer Haynie, Xiaoming Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The essential role of Cited2, a negative regulator for HIF-1alpha, in heart development and neurulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.162371799"}], "href": "https://doi.org/10.1073/pnas.162371799"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12149478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12149478"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Simon D Bamforth, José Bragança, Cassandra R Farthing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1446"}], "href": "https://doi.org/10.1038/ng1446"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15475956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15475956"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Juan Pedro Martinez Barbera, Tristan A Rodriguez, Nicholas D E Greene, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Folic acid prevents exencephaly in Cited2 deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/11.3.283"}], "href": "https://doi.org/10.1093/hmg/11.3.283"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11823447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11823447"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wolfgang J Weninger, Kylie Lopes Floro, Michael B Bennett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.01696"}], "href": "https://doi.org/10.1242/dev.01696"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15750185"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15750185"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "S L Withington, A N Scott, D N Saunders, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of Cited2 affects trophoblast formation and vascularization of the mouse placenta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ydbio.2006.02.025"}], "href": "https://doi.org/10.1016/j.ydbio.2006.02.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16579983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16579983"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "José Bragança, Jyrki J Eloranta, Simon D Bamforth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M208144200"}], "href": "https://doi.org/10.1074/jbc.M208144200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12586840"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12586840"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Silke Sperling, Christina H Grimm, Ilona Dunkel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and functional analysis of CITED2 mutations in patients with congenital heart defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.20262"}], "href": "https://doi.org/10.1002/humu.20262"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16287139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16287139"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yan Liu, Fengyu Wang, Yuan Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variations of CITED2 are associated with congenital heart disease (CHD) in Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0098157"}], "href": "https://doi.org/10.1371/journal.pone.0098157"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24848765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24848765"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Eric S Tien, John W Davis, John P Vanden Heuvel "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the CREB-binding protein/p300-interacting protein CITED2 as a peroxisome proliferator-activated receptor alpha coregulator."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M401489200"}], "href": "https://doi.org/10.1074/jbc.M401489200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15051727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15051727"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Y-T Chou, H Wang, Y Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cited2 modulates TGF-beta-mediated upregulation of MMP9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209552"}], "href": "https://doi.org/10.1038/sj.onc.1209552"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16619037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16619037"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Kamil R Kranc, Simon D Bamforth, José Bragança, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional coactivator Cited2 induces Bmi1 and Mel18 and controls fibroblast proliferation via Ink4a/ARF."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.21.7658-7666.2003"}], "href": "https://doi.org/10.1128/MCB.23.21.7658-7666.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14560011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14560011"}]}]}]}
Synonyms	MRG-1, VSD2, ASD8, P35SRJ
Proteins	CITE2_HUMAN
NCBI Gene ID	10370
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CITED2 has 15,035 functional associations with biological entities spanning 8 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) extracted from 130 datasets.

Click the + buttons to view associations for CITED2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CITED2 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 CITED2 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 CITED2 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 CITED2 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 CITED2 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 CITED2 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 CITED2 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 CITED2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving CITED2 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CITED2 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 CITED2 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 CITED2 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 CITED2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CITED2 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 CITED2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CITED2 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 CITED2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CITED2 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 CITED2 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 CITED2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of CITED2 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 CITED2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CITED2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CITED2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CITED2 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 CITED2 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 CITED2 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 CITED2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing CITED2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CITED2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CITED2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CITED2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CITED2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CITED2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CITED2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CITED2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CITED2 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 CITED2 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 CITED2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CITED2 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 CITED2 gene from the ENCODE Histone Modification Site Profiles dataset.