SLC9A2: Sodium/Hydrogen Exchanger 2 (NHE2)
Solute Carrier Family 9 Member A2 – Ion Transport and pH Regulation
Gene Information Card
| Symbol | SLC9A2 |
|---|---|
| Full Name | Solute Carrier Family 9 Member A2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 2q12.1 |
| NCBI Gene ID | 6548 ncbi.nlm.nih.gov/gene/6548 |
| Ensembl ID | ENSG00000115616 |
| UniProt ID | Q9UBY0 |
| OMIM ID | 600310 |
| HGNC ID | 11073 |
| Aliases | NHE2, APNH, FLJ20171 |
Description
SLC9A2 encodes the sodium/hydrogen exchanger 2 (NHE2), a transmembrane protein that mediates electroneutral exchange of Na+ for H+ across the plasma membrane. This exchanger plays a critical role in intracellular pH homeostasis, cell volume regulation, and ion transport, particularly in epithelial tissues of the gastrointestinal tract and kidney.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital sodium diarrhea | Loss of NHE2 function impairs intestinal Na+ absorption, leading to osmotic diarrhea | PMID: 25713288; ClinVar |
| Inflammatory bowel disease (susceptibility) | Altered pH regulation and ion transport in colonic epithelium may contribute to mucosal inflammation | PMID: 22197931; GWAS catalog |
| Hypertension (animal model) | NHE2 dysfunction affects renal Na+ handling and blood pressure regulation | PMID: 11500513; OMIM #600310 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small intestine | 27.8 | High |
| Colon | 22.1 | High |
| Kidney | 15.3 | Medium |
| Stomach | 12.4 | Medium |
| Liver | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (intestinal) | 28.5 | High expression |
| HEK 293 (embryonic kidney) | 18.2 | Moderate expression |
| HepG2 (liver) | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1582C>T (p.Arg528*) | Nonsense | <0.01% | Premature stop; loss of function |
| c.1124G>A (p.Arg375Gln) | Missense | <0.01% | Reduced Na+/H+ exchange activity |
| c.1961_1962del (p.Val654Alafs*12) | Frameshift | <0.01% | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift variants (e.g., p.Arg528*, p.Val654Alafs*12) lead to truncated, non-functional NHE2 protein.
Gain of Function (GOF)
No gain-of-function mutations reported in SLC9A2.
Dominant Negative (DN)
No dominant-negative mutations reported in SLC9A2.
View complete mutation data：
Gene Ontology (GO)
| • sodium:proton antiporter activity (GO:0015385) | • regulation of pH (GO:0006885) |
| • sodium ion transport (GO:0006814) | • membrane (GO:0016020) |
| • plasma membrane (GO:0005886) |
Pathways
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Transport of inorganic cations/anions and amino acids/oligopeptides (Reactome: R-HSA-425393)
• SLC-mediated transmembrane transport (Reactome: R-HSA-425407)
Protein Summary
NHE2 (UniProt Q9UBY0) is a 812-amino-acid multi-pass membrane protein with 12 transmembrane domains. It functions as an electroneutral Na+/H+ antiporter, critical for pH and volume homeostasis in epithelial cells. The protein is predominantly expressed in the brush border of intestinal and renal epithelia, where it mediates Na+ absorption and H+ secretion. NHE2 activity is regulated by phosphorylation, pH, and interactions with scaffolding proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC9A2 Knockout HEK293 Cell Line | EDJ-KQ5778 | Human | 6549 | Details Get a Quote |
| SLC9A2 Knockout A-549 Cell Line | EDJ-KQ29196 | Human | 6549 | Details Get a Quote |
| SLC9A2 Knockout HCT 116 Cell Line | EDJ-KQ29197 | Human | 6549 | Details Get a Quote |
| SLC9A2 Knockout HeLa Cell Line | EDJ-KQ29198 | Human | 6549 | Details Get a Quote |
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