SLC4A8: Solute Carrier Family 4 Member 8
Sodium-driven chloride/bicarbonate exchanger involved in pH regulation and ion transport
Gene Information Card
| Symbol | SLC4A8 |
|---|---|
| Full Name | Solute Carrier Family 4 Member 8 |
| Gene Type | Protein-coding |
| Chromosomal Location | 12q13.13 |
| NCBI Gene ID | 9498 ncbi.nlm.nih.gov/gene/9498 |
| Ensembl ID | ENSG00000135446 |
| UniProt ID | Q2Y0W8 |
| OMIM ID | 605312 |
| HGNC ID | 11030 |
| Aliases | NDCBE, SLC4A9, NBC3, kNBC3 |
Description
SLC4A8 encodes a sodium-driven chloride/bicarbonate exchanger (NDCBE) that mediates electroneutral Na+-dependent Cl-/HCO3- exchange. This protein plays a critical role in intracellular pH regulation, bicarbonate transport, and ion homeostasis in various tissues, including kidney, brain, and testis. Mutations in SLC4A8 are associated with neurodevelopmental disorders and renal tubular acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia and intellectual disability | Loss-of-function mutations impair pH regulation in neurons, leading to altered neuronal excitability and synaptic function | ClinVar, OMIM |
| Renal tubular acidosis | Defective bicarbonate reabsorption in kidney proximal tubules due to impaired Na+-dependent Cl-/HCO3- exchange | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Testis | 6.1 | Low |
| Liver | 2.4 | Low |
| Heart | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| SH-SY5Y | 9.7 | Medium expression |
| HepG2 | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1432C>T (p.Arg478*) | Nonsense | <0.01% | Loss of function; premature stop codon |
| c.2156G>A (p.Arg719His) | Missense | <0.01% | Reduced transport activity |
| c.2870T>C (p.Leu957Pro) | Missense | <0.01% | Impaired protein folding and trafficking |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce or abolish Na+-dependent Cl-/HCO3- exchange activity, leading to pH dysregulation.
Gain of Function (GOF)
Not reported in literature or curated databases.
Dominant Negative (DN)
Not reported; SLC4A8 functions as a monomer, and dominant-negative effects are unlikely.
View complete mutation data：
Gene Ontology (GO)
| • symporter activity (GO:0015293) | • bicarbonate transport (GO:0015701) |
| • plasma membrane (GO:0005886) | • anion transport (GO:0006820) |
| • regulation of intracellular pH (GO:0051453) |
Pathways
• Bicarbonate transporters (Reactome: R-HSA-425393)
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
Protein Summary
SLC4A8 encodes a 1,044-amino acid transmembrane protein (NDCBE) with 14 predicted transmembrane domains. It functions as an electroneutral Na+-driven Cl-/HCO3- exchanger, coupling the influx of Na+ and HCO3- to the efflux of Cl-. The protein is expressed predominantly in kidney and brain, where it regulates intracellular pH and transepithelial bicarbonate transport. Structural studies indicate a homodimeric assembly, with each monomer containing a core transport domain and a regulatory domain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC4A8 Knockout HEK293 Cell Line | EDJ-KQ6610 | Human | 9498 | Details Get a Quote |
| SLC4A8 Knockout A-549 Cell Line | EDJ-KQ30847 | Human | 9498 | Details Get a Quote |
| SLC4A8 Knockout HeLa Cell Line | EDJ-KQ55180 | Human | 9498 | Details Get a Quote |
| SLC4A8 Knockout HCT 116 Cell Line | EDJ-KQ72120 | Human | 9498 | Details Get a Quote |
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