UCP2 Gene

HGNC Family	Solute carriers (SLC)
Name	uncoupling protein 2 (mitochondrial, proton carrier)
Description	Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known. UCPs contain the three homologous protein domains of MACPs. This gene is expressed in many tissues, with the greatest expression in skeletal muscle. It is thought to play a role in nonshivering thermogenesis, obesity and diabetes. Chromosomal order is 5'-UCP3-UCP2-3'. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMitochondrial uncoupling protein 2 (UCP2) acts as a pivotal modulator of mitochondrial function by fine‐tuning the production of reactive oxygen species (ROS) and preserving cellular integrity under stress. In several models of acute neural injury and cardiac stress, enhanced UCP2 expression mediates “mild uncoupling” that attenuates mitochondrial calcium overload, inhibits apoptotic pathways, and minimizes free‐radical damage. Such protective actions have been documented in experimental stroke, traumatic brain injury, global cerebral ischemia, seizure‐related stress, dopaminergic cell toxicity, endothelial dysfunction, and even in invertebrate models where neuronal UCP2 expression prolongs lifespan by reducing oxidative damage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its antioxidant role, UCP2 serves as an important metabolic regulator that governs substrate utilization and intercompartmental metabolite trafficking. UCP2 can redirect cellular metabolism by acting as a “substrate shunt” to limit mitochondrial glucose oxidation while favoring glycolysis, and it functions as a transporter of key C4 tricarboxylic acid cycle intermediates—thereby modulating glutaminolysis. In addition, UCP2 influences mitochondrial Ca²⁺ uptake, which is critical for the regulation of oxidative phosphorylation, and its activity in pancreatic islet cells impacts both insulin and glucagon secretion. Genetic studies have identified common promoter and coding polymorphisms that alter UCP2 expression in adipose tissue and beta‐cells, thereby linking its functional status to obesity, type 2 diabetes, and overall metabolic flexibility. These multifaceted roles have been substantiated by investigations in pluripotent stem cells, isolated mitochondria, and genetic association studies, which collectively underscore UCP2’s contribution to energy homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancerous contexts, UCP2 appears to adopt a dual‐edged role that supports tumor cell survival and metabolic adaptation. Increased UCP2 levels in various malignancies, including colon, leukemia, breast, lung, and pancreatic ductal adenocarcinoma, promote a shift toward aerobic glycolysis (the Warburg effect) and diminish ROS accumulation, thereby conferring chemoresistance and anti‐apoptotic advantages. In KRAS‐mutant pancreatic cancer cells, for example, UCP2’s aspartate transport function links mitochondrial and cytosolic metabolism to facilitate tumor growth. Collectively, these findings imply that modulating UCP2 activity may represent a promising therapeutic strategy to counteract tumor progression and overcome treatment resistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yasushi Teshima, Masaharu Akao, Steven P Jones, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Association of UCP2 -866 G/A polymorphism with chronic inflammatory diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/gene.2009.29"}], "href": "https://doi.org/10.1038/gene.2009.29"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19387457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19387457"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Vanniarajan Ayyasamy, Kjerstin M Owens, Mohamed Mokhtar Desouki, et al. 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Synonyms	SLC25A8, UCPH, BMIQ4
Proteins	UCP2_HUMAN
NCBI Gene ID	7351
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

UCP2 has 13,560 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 124 datasets.

Click the + buttons to view associations for UCP2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

UCP2 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 UCP2 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 UCP2 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 UCP2 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 UCP2 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 UCP2 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 UCP2 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 UCP2 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 UCP2 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 UCP2 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 UCP2 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 UCP2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with UCP2 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 UCP2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of UCP2 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 UCP2 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 UCP2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of UCP2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing UCP2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing UCP2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with UCP2 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 UCP2 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 UCP2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with UCP2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with UCP2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with UCP2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by UCP2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving UCP2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving UCP2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with UCP2 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 UCP2 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 UCP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with UCP2 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 UCP2 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 UCP2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of UCP2 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 UCP2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with UCP2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with UCP2 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 UCP2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with UCP2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.