XPR1 Gene

Name	xenotropic and polytropic retrovirus receptor 1
Description	The protein encoded by this gene is a receptor for the xenotropic and polytropic classes of murine leukemia viruses. The encoded protein is involved in phosphate homeostasis by mediating phosphate export from the cell. Defects in this gene have been associated with idiopathic basal ganglia calcification-6. [provided by RefSeq, Jun 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nXPR1 is the sole known inorganic phosphate exporter in human cells, playing an essential role in maintaining phosphate homeostasis. Mutations in XPR1 have been linked to primary familial brain calcification (PFBC), where impaired phosphate export due to these mutations disrupts normal phosphate regulation in the brain. In PFBC patients, alterations in XPR1—whether affecting its cell‐surface localization or its transport activity—lead to aberrant phosphate accumulation and consequent pathological calcification."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies have revealed that XPR1-mediated phosphate efflux is subject to tight regulation by inositol pyrophosphate signaling. Binding of inositol polyphosphates—including InsP8—to the SPX domain modulates XPR1’s gating, with key basic clusters and a conserved tryptophan residue acting as a molecular switch to control phosphate transport. Moreover, the interplay between phosphate importers (e.g., SLC20A2) and XPR1 ensures the coordination of phosphate uptake and efflux, thereby stabilizing intracellular phosphate and ATP levels. Recent cryo-electron microscopy structures have further detailed the molecular architecture of XPR1, delineating the structural elements that underlie its phosphate export function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these roles in phosphate homeostasis, XPR1 also functions as a receptor for retroviruses and is implicated in diverse pathophysiological conditions, notably cancer. In prostate cells, for example, XPR1 facilitates xenotropic murine leukemia virus entry, while aberrant expression or regulation of XPR1 has been observed in several malignancies—including ovarian, uterine, osteosarcoma, papillary thyroid, and lung adenocarcinoma—where it contributes to tumor cell survival by preventing toxic phosphate accumulation. Its expression is modulated by factors such as microRNAs and interacting proteins like KIDINS220, and alterations in XPR1-related phosphate transport may also underlie conditions such as tumor-induced osteomalacia. Collectively, these findings underscore the multifunctional nature of XPR1, linking its phosphate export and receptor functions to both metabolic and oncogenic processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andrea Legati, Donatella Giovannini, Gaël Nicolas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.3289"}], "href": "https://doi.org/10.1038/ng.3289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25938945"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25938945"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mathieu Anheim, Uriel López-Sánchez, Donatella Giovannini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XPR1 mutations are a rare cause of primary familial brain calcification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00415-016-8166-4"}], "href": "https://doi.org/10.1007/s00415-016-8166-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27230854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27230854"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Uriel López-Sánchez, Gaël Nicolas, Anne-Claire Richard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of XPR1/SLC53A1 variants located outside of the SPX domain in patients with primary familial brain calcification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-43255-x"}], "href": "https://doi.org/10.1038/s41598-019-43255-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31043717"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31043717"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Miranda S Wilson, Henning J Jessen, Adolfo Saiardi "}, {"type": "b", "children": [{"type": "t", "text": "The inositol hexakisphosphate kinases IP6K1 and -2 regulate human cellular phosphate homeostasis, including XPR1-mediated phosphate export."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA119.007848"}], "href": "https://doi.org/10.1074/jbc.RA119.007848"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31186349"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31186349"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xingyao Li, Chunfang Gu, Sarah Hostachy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Control of XPR1-dependent cellular phosphate efflux by InsP"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "8"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " is an exemplar for functionally-exclusive inositol pyrophosphate signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1908830117"}], "href": "https://doi.org/10.1073/pnas.1908830117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32019887"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32019887"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Uriel López-Sánchez, Sandrine Tury, Gaël Nicolas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interplay between primary familial brain calcification-associated SLC20A2 and XPR1 phosphate transporters requires inositol polyphosphates for control of cellular phosphate homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA119.011376"}], "href": "https://doi.org/10.1074/jbc.RA119.011376"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32393577"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32393577"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Rui Yan, Huiwen Chen, Chuanyu Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human XPR1 structures reveal phosphate export mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-024-07852-9"}], "href": "https://doi.org/10.1038/s41586-024-07852-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39169184"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39169184"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sushma Bhosle, Suganthi Suppiah, Ross Molinaro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evaluation of cellular determinants required for in vitro xenotropic murine leukemia virus-related virus entry into human prostate cancer and noncancerous cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00274-10"}], "href": "https://doi.org/10.1128/JVI.00274-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20410264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20410264"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Wei-Chao Chen, Qiu-Li Li, Qimei Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of tongue squamous cell carcinoma (TSCC) via activation of NF-κB signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-019-1155-6"}], "href": "https://doi.org/10.1186/s13046-019-1155-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30995931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30995931"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Y Jiang, X Li, J Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The genetic polymorphisms of XPR1 and SCL34A3 are associated with Fanconi syndrome in Chinese patients of tumor-induced osteomalacia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Endocrinol Invest (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s40618-020-01371-w"}], "href": "https://doi.org/10.1007/s40618-020-01371-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32725396"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32725396"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xiaohuan Mao, Shuren Guo, Lan Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circ-XPR1 promotes osteosarcoma proliferation through regulating the miR-214-5p/DDX5 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-020-00412-z"}], "href": "https://doi.org/10.1007/s13577-020-00412-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32920730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32920730"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Huawei Zou, Cheng Xiang "}, {"type": "b", "children": [{"type": "t", "text": "Clinical implication of xenotropic and polytropic retrovirus receptor 1 in papillary thyroid carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhejiang Da Xue Xue Bao Yi Xue Ban (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3724/zdxbyxb-2021-0052"}], "href": "https://doi.org/10.3724/zdxbyxb-2021-0052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34117845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34117845"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yaqiong Hu, Jun Bai, Dandan Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The miR-4732-5p/XPR1 axis suppresses the invasion, metastasis, and epithelial-mesenchymal transition of lung adenocarcinoma "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "via"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " the PI3K/Akt/GSK3β/Snail pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Omics (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1039/d1mo00245g"}], "href": "https://doi.org/10.1039/d1mo00245g"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35388387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35388387"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Daniel P Bondeson, Brenton R Paolella, Adhana Asfaw, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphate dysregulation via the XPR1-KIDINS220 protein complex is a therapeutic vulnerability in ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cancer (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s43018-022-00360-7"}], "href": "https://doi.org/10.1038/s43018-022-00360-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35437317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35437317"}]}]}]}
Synonyms	SYG1, X3, IBGC6, SLC53A1
Proteins	XPR1_HUMAN
NCBI Gene ID	9213
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

XPR1 has 7,494 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 110 datasets.

Click the + buttons to view associations for XPR1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

XPR1 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 XPR1 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 XPR1 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 XPR1 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 XPR1 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 XPR1 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 XPR1 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 XPR1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of XPR1 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 XPR1 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 XPR1 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 XPR1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with XPR1 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 XPR1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of XPR1 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 XPR1 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 XPR1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing XPR1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing XPR1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with XPR1 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 XPR1 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 XPR1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with XPR1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with XPR1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of XPR1 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 XPR1 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 XPR1 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 XPR1 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 XPR1 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 XPR1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with XPR1 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 XPR1 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 XPR1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of XPR1 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 XPR1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with XPR1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with XPR1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with XPR1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing XPR1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of XPR1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of XPR1 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.