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SLC9A5 solute carrier family 9 member A5 [ Homo sapiens (human) ]

Gene ID: 6553, updated on 5-Aug-2026
Official Symbol
SLC9A5provided by HGNC
Official Full Name
solute carrier family 9 member A5provided by HGNC
Primary source
HGNC:HGNC:11078
See related
Ensembl:ENSG00000135740 MIM:600477; AllianceGenome:HGNC:11078
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
NHE5
Summary
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, Jul 2025]
Expression
Biased expression in spleen (RPKM 6.3), testis (RPKM 2.2) and 7 other tissues See more
Orthologs
all
Try the new Gene page
Try the new Transcripts and proteins table
See SLC9A5 in Genome Data Viewer
Location:
16q22.1
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (67248979..67272191)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (73043264..73066486)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (67282882..67306094)

Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10959 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67265259-67265760 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67265761-67266260 Neighboring gene transmembrane protein 208 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7594 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr16:67271286-67272485 Neighboring gene formin homology 2 domain containing 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:67275498-67276171 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:67276172-67276844 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10960 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10961 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10962 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:67279559-67280218 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7595 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7596 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7597 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7598 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67282619-67283120 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67283121-67283620 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:67287038-67287220 Neighboring gene uncharacterized LOC124903701 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:67304537-67304794 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7600 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:67313287-67313468 Neighboring gene pleckstrin homology and RhoGEF domain containing G4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67318282-67319022 Neighboring gene potassium channel tetramerization domain containing 19 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10963 Neighboring gene RN7SK pseudogene 118

Go to nucleotide: Graphics FASTA GenBank

Related articles in PubMed

  1. Molecular cloning and physical and genetic mapping of a novel human Na+/H+ exchanger (NHE5/SLC9A5) to chromosome 16q22.1. Klanke CA, et al. Genomics, 1995 Feb 10. PMID 7759094
  2. Molecular cloning, genomic organization, and functional expression of Na+/H+ exchanger isoform 5 (NHE5) from human brain. Baird NR, et al. J Biol Chem, 1999 Feb 12. PMID 9933641
  3. Clathrin-mediated endocytosis and recycling of the neuron-specific Na+/H+ exchanger NHE5 isoform. Regulation by phosphatidylinositol 3'-kinase and the actin cytoskeleton. Szaszi K, et al. J Biol Chem, 2002 Nov 8. PMID 12205089
  4. Regulation of dendritic spine growth through activity-dependent recruitment of the brain-enriched Na⁺/H⁺ exchanger NHE5. Diering GH, et al. Mol Biol Cell, 2011 Jul 1. PMID 21551074, Free PMC Article
  5. Activation of AMP-activated protein kinase regulates hippocampal neuronal pH by recruiting Na(+)/H(+) exchanger NHE5 to the cell surface. Jinadasa T, et al. J Biol Chem, 2014 Jul 25. PMID 24936055, Free PMC Article

See all (23) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. High NHE5 expression is associated with glioma.
    Title: NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells.
  2. These data reveal a unique role for AMPK and NHE5 in regulating the pH homeostasis of hippocampal neurons during metabolic stress.
    Title: Activation of AMP-activated protein kinase regulates hippocampal neuronal pH by recruiting Na(+)/H(+) exchanger NHE5 to the cell surface.
  3. overexpression of NHE5 inhibits spine growth in response to neuronal activity
    Title: Regulation of dendritic spine growth through activity-dependent recruitment of the brain-enriched Na⁺/H⁺ exchanger NHE5.
  4. discrete elements of an elaborate sorting signal in NHE5 contribute to beta-arrestin2 binding and trafficking along the recycling endosomal pathway.
    Title: CK2 phosphorylation of an acidic Ser/Thr di-isoleucine motif in the Na+/H+ exchanger NHE5 isoform promotes association with beta-arrestin2 and endocytosis.
  5. SCAMP2 regulates NHE5 transit through recycling endosomes and promotes its surface targeting in an Arf6-dependent manner.
    Title: Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5.
  6. observations demonstrate that NHE5 is localized to the recycling endosomal pathway and is dynamically regulated by phosphatidylinositol 3'-kinase and by the state of F-actin assembly
    Title: Clathrin-mediated endocytosis and recycling of the neuron-specific Na+/H+ exchanger NHE5 isoform. Regulation by phosphatidylinositol 3'-kinase and the actin cytoskeleton.
  7. beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform.
    Title: beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform.
  8. RACK1 activates NHE5 both by integrin-dependent and independent pathways, which may coordinate cellular ion homeostasis during cell-matrix adhesion.
    Title: RACK1 associates with NHE5 in focal adhesions and positively regulates the transporter activity.
Submit: New GeneRIF Correction

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

Protein interactions

Protein Gene Interaction Pubs
Nef nef EIPA, a potent and specific inhibitor of Na+/H+ exchanger activity, significantly inhibits the Nef internalization into M2-macrophages, indicating that Nef is imported by Na+/H+ exchanger (solute carrier family 9, subfamily A) PubMed

Go to the HIV-1, Human Interaction Database

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables antiporter activity IEA
Inferred from Electronic Annotation
more info
  
enables arrestin family protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables potassium:proton antiporter activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables sodium:proton antiporter activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables sodium:proton antiporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables sodium:proton antiporter activity IEA
Inferred from Electronic Annotation
more info
  
enables sodium:proton antiporter activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in monoatomic cation transport IEA
Inferred from Electronic Annotation
more info
  
involved_in potassium ion transmembrane transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in proton transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of intracellular pH IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of intracellular pH IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of pH IEA
Inferred from Electronic Annotation
more info
  
involved_in sodium ion import across plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in sodium ion transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in sodium ion transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in sodium ion transmembrane transport TAS
Traceable Author Statement
more info
  
involved_in sodium ion transport IEA
Inferred from Electronic Annotation
more info
  
involved_in transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in dendritic spine membrane IEA
Inferred from Electronic Annotation
more info
  
located_in focal adhesion IDA
Inferred from Direct Assay
more info
 PubMed 
located_in focal adhesion IEA
Inferred from Electronic Annotation
more info
  
located_in membrane IEA
Inferred from Electronic Annotation
more info
  
located_in membrane TAS
Traceable Author Statement
more info
 PubMed 
located_in neuron spine IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane EXP
Inferred from Experiment
more info
 PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in recycling endosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in recycling endosome membrane IEA
Inferred from Electronic Annotation
more info
  
located_in synapse IDA
Inferred from Direct Assay
more info
 PubMed 
located_in synaptic membrane EXP
Inferred from Experiment
more info
 PubMed 
located_in synaptic membrane IEA
Inferred from Electronic Annotation
more info
  
Preferred Names
sodium/hydrogen exchanger 5
Names
NHE-5
Na(+)/H(+) exchanger 5
solute carrier family 9 (sodium/hydrogen exchanger), member 5
solute carrier family 9 member 5
solute carrier family 9, subfamily A (NHE5, cation proton antiporter 5), member 5

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001323971.2 → NP_001310900.1  sodium/hydrogen exchanger 5 isoform 2 precursor

    Status: VALIDATED

    Source sequence(s)
    AC040160
    Conserved Domains (1) summary
    TIGR00840
    Location:41 → 573
    b_cpa1; sodium/hydrogen exchanger 3

  2. NM_001323972.2 → NP_001310901.1  sodium/hydrogen exchanger 5 isoform 3 precursor

    Status: VALIDATED

    Source sequence(s)
    AC040160
    UniProtKB/TrEMBL
    A0ACI8QQC0, A0ACI8TF06
    Related
    ENSP00000598335.1, ENST00000928276.2

  3. NM_001323973.2 → NP_001310902.1  sodium/hydrogen exchanger 5 isoform 4 precursor

    Status: VALIDATED

    Source sequence(s)
    AC040160
    UniProtKB/TrEMBL
    A0ACI8QMH5, A0ACI8QQC0
    Related
    ENSP00000567551.1, ENST00000897492.2
    Conserved Domains (2) summary
    TIGR00840
    Location:41 → 630
    b_cpa1; sodium/hydrogen exchanger 3
    pfam00999
    Location:50 → 455
    Na_H_Exchanger; Sodium/hydrogen exchanger family

  4. NM_001323974.2 → NP_001310903.1  sodium/hydrogen exchanger 5 isoform 5

    Status: VALIDATED

    Source sequence(s)
    AC040160

  5. NM_001323975.2 → NP_001310904.1  sodium/hydrogen exchanger 5 isoform 6

    Status: VALIDATED

    Source sequence(s)
    AC040160
    Conserved Domains (2) summary
    TIGR00840
    Location:1 → 335
    b_cpa1; sodium/hydrogen exchanger 3
    cl01133
    Location:1 → 160
    Na_H_Exchanger; Sodium/hydrogen exchanger family

  6. NM_004594.3 → NP_004585.1  sodium/hydrogen exchanger 5 isoform 1 precursor

    See identical proteins and their annotated locations for NP_004585.1

    Status: VALIDATED

    Source sequence(s)
    AF111173, AL137689, DB475730
    Consensus CDS
    CCDS42178.1
    UniProtKB/Swiss-Prot
    A5PKY7, Q14940, Q9Y626
    UniProtKB/TrEMBL
    A0ACI8QQC0
    Related
    ENSP00000299798.11, ENST00000299798.16
    Conserved Domains (1) summary
    cl25615
    Location:41 → 630
    NhaP2; NhaP-type Na+/H+ and K+/H+ antiporter with C-terminal TrkAC and CorC domains [Energy production and conversion, Inorganic ion transport and metabolism]

RNA

  1. NR_136664.2 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC040160
    Related
    ENST00001052997.1

  2. NR_136665.2 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC040160
    Related
    ENST00000564812.5

  3. NR_136666.2 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC040160

  4. NR_136667.2 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC040160

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

    Range
    67248979..67272191
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047434520.1 → XP_047290476.1  sodium/hydrogen exchanger 5 isoform X2

  2. XM_017023594.2 → XP_016879083.1  sodium/hydrogen exchanger 5 isoform X3

  3. XM_047434519.1 → XP_047290475.1  sodium/hydrogen exchanger 5 isoform X1

    Related
    ENSP00000722813.1, ENST00001052996.1

  4. XM_047434521.1 → XP_047290477.1  sodium/hydrogen exchanger 5 isoform X4

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060940.1 Alternate T2T-CHM13v2.0

    Range
    73043264..73066486
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054313756.1 → XP_054169731.1  sodium/hydrogen exchanger 5 isoform X2

  2. XM_054313757.1 → XP_054169732.1  sodium/hydrogen exchanger 5 isoform X3

  3. XM_054313755.1 → XP_054169730.1  sodium/hydrogen exchanger 5 isoform X1

  4. XM_054313758.1 → XP_054169733.1  sodium/hydrogen exchanger 5 isoform X4

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q14940.2 GenPept UniProtKB/Swiss-Prot:Q14940

Gene LinkOut

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