SLC9A4: Solute Carrier Family 9 Member A4
Sodium/Hydrogen Exchanger 4 (NHE4) – Gene Overview and Biomedical Significance
Gene Information Card
| Symbol | SLC9A4 |
|---|---|
| Full Name | Solute Carrier Family 9 Member A4 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q12.1 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000115977 |
| UniProt ID | Q9Y6R1 |
| OMIM ID | 600421 |
| HGNC ID | 11073 |
| Aliases | NHE4, FLJ20171 |
Description
SLC9A4 (solute carrier family 9 member A4) encodes the sodium/hydrogen exchanger 4 (NHE4), a transmembrane protein that mediates electroneutral exchange of Na+ for H+ across the plasma membrane. NHE4 is involved in intracellular pH regulation, cell volume control, and ion homeostasis. It is predominantly expressed in the kidney, stomach, and intestine, where it plays roles in acid-base balance and electrolyte transport.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gastric cancer | Altered NHE4 expression may contribute to tumorigenesis via dysregulated pH homeostasis | PMID: 25642768 |
| Renal tubular acidosis | Potential involvement in acid-base transport defects; limited direct evidence | ClinVar: uncertain significance |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Stomach | 8.3 | Medium |
| Small intestine | 6.1 | Low |
| Colon | 4.7 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Moderate expression |
| Caco-2 | 9.8 | Intestinal epithelial model |
| HK-2 | 11.4 | Proximal tubule kidney cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Trp) | missense | <0.01% | Unknown functional effect |
| c.567_569del (p.Glu189del) | in-frame deletion | <0.01% | Potential loss of function |
Mutation functional classification
Loss of Function (LOF)
In-frame deletions or nonsense variants likely impair Na+/H+ exchange activity.
Gain of Function (GOF)
Not reported for SLC9A4.
Dominant Negative (DN)
Not documented.
View complete mutation data：
Gene Ontology (GO)
| • sodium:proton antiporter activity (GO:0015385) | • plasma membrane (GO:0005886) |
| • regulation of pH (GO:0006885) | • regulation of intracellular pH (GO:0051453) |
| • sodium ion transport (GO:0006814) |
Pathways
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Transport of inorganic cations/anions and amino acids/oligopeptides (Reactome: R-HSA-425393)
Protein Summary
The SLC9A4 protein (NHE4) is a 798-amino acid integral membrane protein with 12 transmembrane domains. It functions as an electroneutral Na+/H+ antiporter, exchanging extracellular sodium for intracellular protons. NHE4 is activated by intracellular acidification and is regulated by phosphorylation and interaction with accessory proteins. It is critical for maintaining pH and volume in epithelial cells of the kidney and gastrointestinal tract.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC9A4 Knockout HEK293 Cell Line | EDJ-KQ5780 | Human | 389015 | Details Get a Quote |
| SLC9A4 Knockout HeLa Cell Line | EDJ-KQ60058 | Human | 389015 | Details Get a Quote |
| SLC9A4 Knockout A-549 Cell Line | EDJ-KQ68520 | Human | 389015 | Details Get a Quote |
| SLC9A4 Knockout HCT 116 Cell Line | EDJ-KQ76895 | Human | 389015 | Details Get a Quote |
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