SLC9A5 Gene

HGNC Family	Solute carriers (SLC)
Name	solute carrier family 9, subfamily A (NHE5, cation proton antiporter 5), member 5
Description	Enables arrestin family protein binding activity and sodium:proton antiporter activity. Involved in regulation of intracellular pH and sodium ion transmembrane transport. Located in several cellular components, including focal adhesion; neuron spine; and recycling endosome membrane. Implicated in end stage renal disease. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC9A5, the gene encoding the brain‐enriched Na⁺/H⁺ exchanger isoform NHE5, plays a pivotal role in regulating intracellular and local extracellular pH by dynamically cycling between the plasma membrane and recycling endosomes. In nonneuronal and neuronal cells alike, NHE5 localizes both to the cell surface and in endosomal compartments—a distribution governed by clathrin‐dependent endocytosis and fine‐tuned by protein–protein interactions. For instance, studies have shown that NHE5 interacts with β‐arrestins, whose binding to its carboxy terminus decreases its surface abundance, and with regulatory proteins such as RACK1 and SCAMP2 that facilitate its targeting to membrane domains (for details, see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neurons, NHE5 is essential for modulating the pH microenvironment of dendritic spines during synaptic activity. Activation of NMDA receptors triggers the recruitment of NHE5 from intracellular stores to the plasma membrane and specifically to the spine head, where it contributes to a delayed alkalinization following an initial acidification. This localized pH regulation acts as a negative feedback mechanism that constrains excessive activity-induced spine growth, thereby influencing synaptic plasticity (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in synaptic function, emerging evidence implicates NHE5 in the regulation of tumor cell behavior, particularly in glioma. In models of glioma, knockdown of NHE5 disrupts endocytic recycling pathways and reduces the stability of cell adhesion molecules such as β₁-integrin, leading to diminished receptor tyrosine kinase signaling. These changes culminate in inhibited cell proliferation, adhesion, and invasion, suggesting that NHE5 not only contributes to neuronal homeostasis but also plays an important role in tumor growth and invasiveness (refer to."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Katalin Szaszi, Anders Paulsen, Elod Z Szabo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clathrin-mediated endocytosis and recycling of the neuron-specific Na+/H+ exchanger NHE5 isoform. Regulation by phosphatidylinositol 3'-kinase and the actin cytoskeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M206629200"}], "href": "https://doi.org/10.1074/jbc.M206629200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12205089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12205089"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Elöd Z Szabó, Masayuki Numata, Viktoria Lukashova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0407444102"}], "href": "https://doi.org/10.1073/pnas.0407444102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15699339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15699339"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ichiro Onishi, Paulo J C Lin, Graham H Diering, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RACK1 associates with NHE5 in focal adhesions and positively regulates the transporter activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2006.06.011"}], "href": "https://doi.org/10.1016/j.cellsig.2006.06.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16920332"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16920332"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Graham H Diering, John Church, Masayuki Numata "}, {"type": "b", "children": [{"type": "t", "text": "Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M807055200"}], "href": "https://doi.org/10.1074/jbc.M807055200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19276089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19276089"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Graham H Diering, Fergil Mills, Shernaz X Bamji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of dendritic spine growth through activity-dependent recruitment of the brain-enriched Na⁺/H⁺ exchanger NHE5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E11-01-0066"}], "href": "https://doi.org/10.1091/mbc.E11-01-0066"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21551074"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21551074"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Toru Kurata, Vinotheni Rajendran, Steven Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Metastasis (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10585-019-10001-6"}], "href": "https://doi.org/10.1007/s10585-019-10001-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31595389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31595389"}]}]}]}
Synonyms	NHE5
Proteins	SL9A5_HUMAN
NCBI Gene ID	6553
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SLC9A5 has 4,963 functional associations with biological entities spanning 8 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) extracted from 105 datasets.

Click the + buttons to view associations for SLC9A5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC9A5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SLC9A5 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 SLC9A5 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 SLC9A5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SLC9A5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SLC9A5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SLC9A5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	dbGAP Gene-Trait Associations	traits associated with SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 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 SLC9A5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SLC9A5 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 SLC9A5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SLC9A5 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 SLC9A5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SLC9A5 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SLC9A5 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 SLC9A5 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SLC9A5 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 SLC9A5 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of SLC9A5 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 SLC9A5 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.