SLC25A3 Gene

HGNC Family	Solute carriers (SLC)
Name	solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 3
Description	The protein encoded by this gene catalyzes the transport of phosphate into the mitochondrial matrix, either by proton cotransport or in exchange for hydroxyl ions. The protein contains three related segments arranged in tandem which are related to those found in other characterized members of the mitochondrial carrier family. Both the N-terminal and C-terminal regions of this protein protrude toward the cytosol. Multiple alternatively spliced transcript variants have been isolated. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC25A3 encodes a mitochondrial carrier protein with a critical role in maintaining cellular energy and metal homeostasis. Early studies of its transcriptional regulation revealed that the phosphate carrier gene (PiC) is driven by a promoter lacking a TATA box yet enriched in binding sites for factors such as Sp1 and CREB, highlighting a tight tissue‐specific control of its expression required for efficient phosphate import into the matrix."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\nClinical investigations have demonstrated that SLC25A3 functions as the primary transporter of inorganic phosphate into the mitochondrial matrix, an essential process for adenosine triphosphate (ATP) synthesis. Mutations affecting the muscle-specific isoform result in markedly reduced ATP production, contributing to lactic acidosis, hypertrophic cardiomyopathy, and muscular hypotonia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n\nFurther studies exploring SLC25A3 deficiency revealed that when protein levels drop significantly (by more than 85%), maximal oxidative phosphorylation is compromised, and mitochondrial network integrity is disrupted. This deficiency underscores the importance of maintaining appropriate SLC25A3 levels not only for ATP generation but also for preserving mitochondrial morphology and efficiency."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n\nIn addition to its pivotal role in phosphate transport, SLC25A3 has been shown to facilitate copper import into the mitochondrial matrix—a process vital for the maturation of cuproenzymes such as cytochrome c oxidase and superoxide dismutase. Functional assays, including knockdowns in mammalian cells and heterologous expression in yeast, confirm that inadequate SLC25A3 impairs copper delivery, leading to cytochrome c oxidase deficiency, thereby linking copper homeostasis directly to mitochondrial function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n\nRecent work has further expanded the functional landscape of SLC25A3 by uncovering its involvement in immune regulation. Specifically, SLC25A3 interacts with the NLRP3 inflammasome, disrupting the association between NLRP3 and NEK7. This interaction promotes the ubiquitination of NLRP3, ultimately dampening inflammasome activation and providing a mechanistic link between mitochondrial metabolism and innate immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Vito Iacobazzi, Vittoria Infantino, Paola Costanzo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional analysis of the promoter of the mitochondrial phosphate carrier human gene: identification of activator and repressor elements and their transcription factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20050776"}], "href": "https://doi.org/10.1042/BJ20050776"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15984930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15984930"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Johannes A Mayr, Olaf Merkel, Sepp D Kohlwein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/511788"}], "href": "https://doi.org/10.1086/511788"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17273968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17273968"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Erin L Seifert, Aniko Gál, Michelle G Acoba, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Natural and Induced Mitochondrial Phosphate Carrier Loss: DIFFERENTIAL DEPENDENCE OF MITOCHONDRIAL METABOLISM AND DYNAMICS AND CELL SURVIVAL ON THE EXTENT OF DEPLETION."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.744714"}], "href": "https://doi.org/10.1074/jbc.M116.744714"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27780865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27780865"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Aren Boulet, Katherine E Vest, Margaret K Maynard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "c"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " oxidase biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA117.000265"}], "href": "https://doi.org/10.1074/jbc.RA117.000265"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29237729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29237729"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Paul A Cobine, Stanley A Moore, Scot C Leary "}, {"type": "b", "children": [{"type": "t", "text": "Getting out what you put in: Copper in mitochondria and its impacts on human disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2020.118867"}], "href": "https://doi.org/10.1016/j.bbamcr.2020.118867"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32979421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32979421"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Feng Xiao, Yaling Jia, Simeng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SLC25A3 negatively regulates NLRP3 inflammasome activation by restricting the function of NLRP3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2024.107233"}], "href": "https://doi.org/10.1016/j.jbc.2024.107233"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38552738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38552738"}]}]}]}
Synonyms	PTP, OK/SW-CL.48, PHC
Proteins	MPCP_HUMAN
NCBI Gene ID	5250
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SLC25A3 has 9,895 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 122 datasets.

Click the + buttons to view associations for SLC25A3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SLC25A3 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 SLC25A3 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 SLC25A3 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 SLC25A3 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 SLC25A3 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 SLC25A3 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 SLC25A3 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 SLC25A3 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 SLC25A3 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 SLC25A3 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 SLC25A3 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 SLC25A3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC25A3 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 SLC25A3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SLC25A3 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 SLC25A3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SLC25A3 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 SLC25A3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with SLC25A3 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SLC25A3 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SLC25A3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SLC25A3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SLC25A3 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 SLC25A3 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 SLC25A3 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 SLC25A3 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 SLC25A3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SLC25A3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SLC25A3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SLC25A3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SLC25A3 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 SLC25A3 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 SLC25A3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SLC25A3 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 SLC25A3 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 SLC25A3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SLC25A3 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 SLC25A3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SLC25A3 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 SLC25A3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SLC25A3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.