SLC9A8 (Solute Carrier Family 9 Member A8)
Sodium/Hydrogen Exchanger 8 (NHE8) – Gene and Protein Overview
Gene Information Card
| Symbol | SLC9A8 |
|---|---|
| Full Name | Solute Carrier Family 9 Member A8 |
| Gene Type | Protein-coding |
| Chromosomal Location | 20q13.13 |
| NCBI Gene ID | 23315 ncbi.nlm.nih.gov/gene/23315 |
| Ensembl ID | ENSG00000101210 |
| UniProt ID | Q9Y2M0 |
| OMIM ID | 612730 |
| HGNC ID | 20662 |
| Aliases | NHE8, MGC138207, MGC138209 |
Description
SLC9A8 (Solute Carrier Family 9 Member A8) encodes the sodium/hydrogen exchanger 8 (NHE8), a transmembrane protein that mediates electroneutral exchange of Na+ for H+ across cellular membranes. NHE8 is involved in intracellular pH regulation, sodium homeostasis, and endosomal/lysosomal function. It is widely expressed, with highest levels in kidney, intestine, and brain.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital sodium diarrhea (CSD) | Loss-of-function mutations in SLC9A8 impair intestinal Na+/H+ exchange, leading to severe neonatal diarrhea, metabolic acidosis, and electrolyte imbalance. | ClinVar, OMIM |
| Microvillus inclusion disease (MVID)-like phenotype | Disruption of NHE8 trafficking or function may contribute to enterocyte brush border defects and chronic diarrhea. | PubMed, OMIM |
| Neurodevelopmental disorder with hypotonia and seizures | Rare missense variants in SLC9A8 have been associated with developmental delay, hypotonia, and epilepsy. | ClinVar, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | High |
| Small intestine | 10.8 | High |
| Brain | 6.2 | Medium |
| Liver | 4.1 | Medium |
| Heart | 2.3 | Low |
| Skeletal muscle | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 8.9 | High expression in kidney-derived line |
| Caco-2 | 7.4 | Intestinal epithelial cell line |
| SH-SY5Y | 5.1 | Neuroblastoma cell line |
| HepG2 | 3.8 | Hepatocellular carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | Rare | Loss of function; associated with congenital sodium diarrhea |
| c.1462G>A (p.Glu488Lys) | Missense | Rare | Likely pathogenic; reported in neurodevelopmental disorder |
| c.1745_1746del (p.Leu582fs) | Frameshift | Rare | Loss of function; truncation of C-terminal domain |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations that disrupt Na+/H+ exchange activity or protein stability, leading to congenital sodium diarrhea and other phenotypes.
Gain of Function (GOF)
No gain-of-function mutations reported in SLC9A8.
Dominant Negative (DN)
Not established; most pathogenic variants are recessive or de novo.
View complete mutation data：
Gene Ontology (GO)
| • solute:proton antiporter activity (GO:0015299) | • regulation of pH (GO:0006885) |
| • transmembrane transport (GO:0055085) | • integral component of membrane (GO:0016021) |
| • lysosome (GO:0005764) | • endosome (GO:0005768) |
Pathways
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• SLC-mediated transmembrane transport (Reactome: R-HSA-425407)
• Na+/H+ exchange (KEGG: map04970)
Protein Summary
NHE8 (UniProt Q9Y2M0) is a 725-amino acid multi-pass transmembrane protein with 10-12 predicted transmembrane helices. It functions as an electroneutral Na+/H+ antiporter, regulating intracellular pH and sodium concentration. NHE8 localizes to the apical membrane of renal proximal tubule cells and intestinal enterocytes, as well as to endosomes and lysosomes. Its activity is modulated by pH, phosphorylation, and interaction with regulatory proteins. Defects in NHE8 cause congenital sodium diarrhea and are implicated in neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC9A8 Knockout HEK293 Cell Line | EDJ-KQ7959 | Human | 23315 | Details Get a Quote |
| SLC9A8 Knockout A-549 Cell Line | EDJ-KQ33642 | Human | 23315 | Details Get a Quote |
| SLC9A8 Knockout HCT 116 Cell Line | EDJ-KQ33643 | Human | 23315 | Details Get a Quote |
| SLC9A8 Knockout HeLa Cell Line | EDJ-KQ33644 | Human | 23315 | Details Get a Quote |
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