SLC9A1: Solute Carrier Family 9 Member A1
Na+/H+ Exchanger 1 (NHE1) – Key Regulator of Intracellular pH and Ion Homeostasis
Gene Information Card
| Symbol | SLC9A1 |
|---|---|
| Full Name | Solute Carrier Family 9 Member A1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.11 |
| NCBI Gene ID | 6548 ncbi.nlm.nih.gov/gene/6548 |
| Ensembl ID | ENSG00000090020 |
| UniProt ID | P19634 |
| OMIM ID | 107310 |
| HGNC ID | 11071 |
| Aliases | NHE1, APNH, FLJ42224 |
Description
SLC9A1 encodes the Na+/H+ exchanger 1 (NHE1), a ubiquitously expressed integral membrane protein that mediates electroneutral exchange of extracellular Na+ for intracellular H+. This exchanger plays a critical role in regulating intracellular pH, cell volume, and sodium homeostasis. NHE1 is involved in cell proliferation, migration, and differentiation, and its dysregulation is linked to various diseases including cancer, hypertension, and cardiac hypertrophy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Liddle syndrome | Gain-of-function mutations increase Na+ reabsorption, leading to hypertension | PMID: 10471494 |
| Essential hypertension | Increased NHE1 activity contributes to vascular smooth muscle cell alkalinization and hypercontractility | PMID: 15604330 |
| Cardiac hypertrophy | NHE1 overactivity promotes cardiomyocyte hypertrophy and fibrosis | PMID: 18660428 |
| Cancer (multiple types) | NHE1 upregulation facilitates tumor cell invasion and metastasis by alkalinizing cytoplasm and acidifying extracellular matrix | PMID: 23563182 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Heart | 10.2 | Medium |
| Brain | 8.9 | Medium |
| Liver | 6.3 | Low |
| Lung | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | High expression |
| HeLa | 11.8 | Medium expression |
| A549 | 9.4 | Medium expression |
| MCF7 | 7.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.688C>T (p.Arg230Cys) | Missense | <0.01% | Reduced Na+/H+ exchange activity |
| c.1129G>A (p.Gly377Ser) | Missense | <0.01% | Altered pH sensitivity |
| c.1682G>A (p.Arg561His) | Missense | <0.01% | Gain-of-function, associated with hypertension |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg230Cys reduce exchanger activity, impairing pH regulation.
Gain of Function (GOF)
Mutations such as p.Arg561His increase Na+/H+ exchange, linked to hypertension.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Na+/H+ exchange (Reactome: R-HSA-425986)
• Cardiac conduction (Reactome: R-HSA-5576891)
Protein Summary
NHE1 is a 10-12 transmembrane domain protein with a large cytoplasmic C-terminal regulatory domain. It functions as a homodimer and is activated by various stimuli including growth factors, hormones, and mechanical stress. The protein is essential for maintaining intracellular pH and is implicated in cell cycle progression, cell migration, and tumor metastasis. Its activity is regulated by phosphorylation, interaction with calmodulin, and other binding partners.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC9A1 Knockout HEK293 Cell Line | EDJ-KQ1430 | Human | 6548 | Details Get a Quote |
| SLC9A1 Knockout A-549 Cell Line | EDJ-KQ20975 | Human | 6548 | Details Get a Quote |
| SLC9A1 Knockout HCT 116 Cell Line | EDJ-KQ20976 | Human | 6548 | Details Get a Quote |
| SLC9A1 Knockout HeLa Cell Line | EDJ-KQ20977 | Human | 6548 | Details Get a Quote |
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