FXYD5 Gene

Name	FXYD domain containing ion transport regulator 5
Description	This gene encodes a member of a family of small membrane proteins that share a 35-amino acid signature sequence domain, beginning with the sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator. Mouse FXYD5 has been termed RIC (Related to Ion Channel). FXYD2, also known as the gamma subunit of the Na,K-ATPase, regulates the properties of that enzyme. FXYD1 (phospholemman), FXYD2 (gamma), FXYD3 (MAT-8), FXYD4 (CHIF), and FXYD5 (RIC) have been shown to induce channel activity in experimental expression systems. Transmembrane topology has been established for two family members (FXYD1 and FXYD2), with the N-terminus extracellular and the C-terminus on the cytoplasmic side of the membrane. This gene product, FXYD5, is a glycoprotein that functions in the up-regulation of chemokine production, and it is involved in the reduction of cell adhesion via its ability to down-regulate E-cadherin. It also promotes metastasis, and has been linked to a variety of cancers. Alternative splicing results in multiple transcript variants. [RefSeq curation by Kathleen J. Sweadner, Ph.D., sweadner@helix.mgh.harvard.edu., Sep 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FXYD5 (also known as dysadherin) is a unique, single‐span membrane protein belonging to the FXYD family of tissue‐specific regulators of the Na,K‐ATPase. Similar to its family members, FXYD5 interacts with the Na,K‐ATPase to modulate its transport kinetics—increasing the maximal pump velocity (V<sub>max</sub>) and altering ion affinities—while its transmembrane domain is critical for forming high‐affinity complexes with the pump (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Moreover, FXYD5 displays additional functions that extend beyond ion transport regulation. Its expression is frequently upregulated in various cancers, where it downregulates E‐cadherin and weakens cell–cell adhesion by interfering with adhesive interactions mediated by the β1‐subunit of the Na,K‐ATPase. This anti‐adhesive activity—dependent on its extracellular O‐glycosylated domain and transmembrane interactions—leads to disruption of intercellular junctions, reorganization of actin structures, and ultimately promotes a more mobile, invasive phenotype (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to altering cell adhesion, FXYD5 can engage in pro‐metastatic signaling. For instance, its upregulation in ovarian cancer has been linked to enhanced transforming growth factor‐β (TGF‑β) signaling and sustained epithelial–mesenchymal transition (EMT), thereby fostering tumor metastasis and predicting poor patient survival (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, FXYD5 influences the tumor microenvironment by increasing the surface expression of receptors—resulting in augmented secretion of chemokines such as CCL2—which may further enhance inflammatory and pro‐survival signals that benefit cancer progression (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, FXYD5 functions dually as a modulator of Na,K‐ATPase activity and as a promoter of cancer cell invasion and metastasis. Its ability to alter ion pump kinetics, disrupt cell–cell adhesion, and stimulate pro‐metastatic signaling pathways underscores its potential as both a prognostic marker and a therapeutic target in diverse carcinomas.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Irina Lubarski, Kaarina Pihakaski-Maunsbach, Steven J D Karlish, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction with the Na,K-ATPase and tissue distribution of FXYD5 (related to ion channel)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M506397200"}], "href": "https://doi.org/10.1074/jbc.M506397200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16148001"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16148001"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Irina Lubarski, Steven J D Karlish, Haim Garty "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional interactions between FXYD5 and the Na+-K+-ATPase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00367.2007"}], "href": "https://doi.org/10.1152/ajprenal.00367.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17881459"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17881459"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Timothy J Miller, Pamela B Davis "}, {"type": "b", "children": [{"type": "t", "text": "FXYD5 modulates Na+ absorption and is increased in cystic fibrosis airway epithelia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00430.2007"}], "href": "https://doi.org/10.1152/ajplung.00430.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18263667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18263667"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Elmira Tokhtaeva, Haying Sun, Nimrod Deiss-Yehiely, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.186148"}], "href": "https://doi.org/10.1242/jcs.186148"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27142834"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27142834"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Irina Lubarski, Carol Asher, Haim Garty "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of cell polarization by the Na+-K+-ATPase-associated protein FXYD5 (dysadherin)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00042.2014"}], "href": "https://doi.org/10.1152/ajpcell.00042.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24717576"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24717576"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yang Bai, Liang-Dong Li, Jun Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A FXYD5/TGF‑β/SMAD positive feedback loop drives epithelial‑to‑mesenchymal transition and promotes tumor growth and metastasis in ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2019.4911"}], "href": "https://doi.org/10.3892/ijo.2019.4911"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31746425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31746425"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Irina Lubarski-Gotliv, Carol Asher, Laura A Dada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FXYD5 Protein Has a Pro-inflammatory Role in Epithelial Cells."}]}, {"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.M115.699041"}], "href": "https://doi.org/10.1074/jbc.M115.699041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27006401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27006401"}]}]}]}
Synonyms	PRO6241, KCT1, OIT2, RIC, IWU1, DYSAD, HSPC113
Proteins	FXYD5_HUMAN
NCBI Gene ID	53827
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

FXYD5 has 8,254 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 105 datasets.

Click the + buttons to view associations for FXYD5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

FXYD5 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 FXYD5 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 FXYD5 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of FXYD5 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 FXYD5 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 FXYD5 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 FXYD5 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 FXYD5 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of FXYD5 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 FXYD5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with FXYD5 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 FXYD5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of FXYD5 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 FXYD5 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 FXYD5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing FXYD5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing FXYD5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing FXYD5 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 FXYD5 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 FXYD5 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 FXYD5 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 FXYD5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with FXYD5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with FXYD5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with FXYD5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with FXYD5 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by FXYD5 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 FXYD5 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 FXYD5 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 FXYD5 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 FXYD5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with FXYD5 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 FXYD5 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 FXYD5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of FXYD5 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 FXYD5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with FXYD5 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with FXYD5 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 FXYD5 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with FXYD5 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 FXYD5 from the GeneSigDB Published Gene Signatures dataset.