SLC4A2: Anion Exchange Protein 2 (AE2) – Gene Overview
Comprehensive biomedical profile of the SLC4A2 gene, including genomic context, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | SLC4A2 |
|---|---|
| Full Name | Solute Carrier Family 4 Member 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 7q36.1 |
| NCBI Gene ID | 6522 ncbi.nlm.nih.gov/gene/6522 |
| Ensembl ID | ENSG00000164889 |
| UniProt ID | P04920 |
| OMIM ID | 109280 |
| HGNC ID | 11026 |
| Aliases | AE2, BND3L, EPB3L1, HKB3, NB3 |
Description
SLC4A2 (Solute Carrier Family 4 Member 2) encodes the anion exchange protein 2 (AE2), a transmembrane chloride/bicarbonate exchanger. AE2 mediates electroneutral exchange of Cl⁻ for HCO₃⁻ across the plasma membrane, playing critical roles in intracellular pH regulation, bicarbonate transport, and acid-base homeostasis. The gene is widely expressed, with highest levels in kidney, stomach, and erythroid cells. Alternative splicing generates multiple isoforms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Renal tubular acidosis (distal) | Impaired Cl⁻/HCO₃⁻ exchange in renal intercalated cells leads to defective acid secretion | ClinVar, OMIM #109280 |
| Osteopetrosis (autosomal recessive) | Loss of AE2 function in osteoclasts disrupts bone resorption | OMIM #259700, PubMed |
| Primary biliary cholangitis (susceptibility) | AE2 dysfunction in cholangiocytes impairs biliary bicarbonate secretion | GWAS, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 32.5 | High |
| Stomach | 28.1 | High |
| Small intestine | 18.7 | Medium |
| Liver | 12.3 | Medium |
| Spleen | 8.9 | Low |
| Lung | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 45.2 | High expression |
| HepG2 | 22.8 | Moderate expression |
| Caco-2 | 19.5 | Moderate expression |
| K562 | 12.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1765C>T (p.Arg589*) | Nonsense | <0.01% | Premature stop, loss of function |
| c.2144G>A (p.Arg715Gln) | Missense | <0.01% | Impaired anion exchange activity |
| c.2602C>T (p.Arg868Trp) | Missense | <0.01% | Reduced membrane expression |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense variants (e.g., p.Arg589*, p.Arg715Gln) that reduce or abolish Cl⁻/HCO₃⁻ exchange activity.
Gain of Function (GOF)
Not reported for SLC4A2.
Dominant Negative (DN)
Not reported for SLC4A2.
View complete mutation data：
Gene Ontology (GO)
| • inorganic anion exchanger activity (GO:0005452) | • bicarbonate transmembrane transporter activity (GO:0015106) |
| • antiporter activity (GO:0015297) | • plasma membrane (GO:0005886) |
| • basolateral plasma membrane (GO:0016323) | • anion transport (GO:0006820) |
| • regulation of intracellular pH (GO:0051453) |
Pathways
• REACT:17015 – Transport of inorganic cations/anions
• REACT:17016 – Bicarbonate transporters
• REACT:17017 – Ion channel and transporter regulation
Protein Summary
AE2 is a 1237-amino-acid multi-pass transmembrane protein with 12–14 transmembrane domains. It functions as a homodimer and is glycosylated. The protein is essential for bicarbonate secretion in epithelia, acid-base balance in kidney, and bone remodeling in osteoclasts. Mutations cause distal renal tubular acidosis and osteopetrosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC4A2 Knockout HEK293 Cell Line | EDJ-KQ5763 | Human | 6522 | Details Get a Quote |
| SLC4A2 Knockout A-549 Cell Line | EDJ-KQ27920 | Human | 6522 | Details Get a Quote |
| SLC4A2 Knockout HCT 116 Cell Line | EDC08650 | Human | 6522 | Details Get a Quote |
| SLC4A2 Knockout HeLa Cell Line | EDJ-KQ29179 | Human | 6522 | Details Get a Quote |
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