SLC26A3 (DRA): Chloride/Bicarbonate Exchanger in Intestinal Ion Homeostasis
SLC26A3 encodes the downregulated in adenoma (DRA) protein, a critical anion exchanger in the colon, linked to congenital chloride diarrhea and inflammatory bowel disease.
Gene Information Card
| Symbol | SLC26A3 |
|---|---|
| Full Name | Solute carrier family 26 member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q31.1 (GRCh38: 7:107,765,186-107,803,225) |
| NCBI Gene ID | 1811 ncbi.nlm.nih.gov/gene/1811 |
| Ensembl ID | ENSG00000091138 |
| UniProt ID | P40879 |
| OMIM ID | 126650 |
| HGNC ID | 11018 |
| Aliases | DRA, CLD, DIAR8, downregulated in adenoma |
Description
SLC26A3 encodes the DRA (downregulated in adenoma) protein, a member of the SLC26 sulfate/anion transporter family. It functions as an electroneutral chloride/bicarbonate (Cl-/HCO3-) exchanger, primarily expressed in the apical membrane of intestinal epithelial cells, especially in the colon. DRA plays a crucial role in maintaining intestinal ion and fluid homeostasis by mediating chloride absorption and bicarbonate secretion. Mutations in SLC26A3 cause congenital chloride diarrhea (CLD), an autosomal recessive disorder characterized by watery diarrhea, metabolic alkalosis, and electrolyte imbalances. Additionally, altered SLC26A3 expression has been implicated in inflammatory bowel disease (IBD) and colorectal cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital chloride diarrhea (CLD) | Loss-of-function mutations in SLC26A3 impair Cl-/HCO3- exchange in the ileum and colon, leading to chloride-rich diarrhea, metabolic alkalosis, and hypochloremia. | OMIM #126650; ClinVar; multiple pathogenic variants documented |
| Inflammatory bowel disease (IBD) | Reduced SLC26A3 expression in colonic epithelium is associated with impaired barrier function and altered ion transport, contributing to IBD pathogenesis. | Studies show decreased DRA expression in ulcerative colitis and Crohn's disease (e.g., PMID: 23349068) |
| Colorectal cancer | SLC26A3 is downregulated in adenomas and colorectal cancer tissues; loss of DRA may promote tumorigenesis via altered cellular pH and ion homeostasis. | Gene expression analyses (e.g., TCGA) and functional studies (e.g., PMID: 25452270) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | High (nTPM ~ 200-300) | Highest expression in the colon, particularly in surface epithelial cells |
| Small intestine | Moderate (nTPM ~ 50-100) | Expressed in ileum and duodenum, lower than colon |
| Kidney | Low (nTPM ~ 5-10) | Minimal expression in renal tubules |
| Liver | Low (nTPM ~ 1-5) | Very low expression |
| Pancreas | Low (nTPM ~ 1-5) | Minimal expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 | High | Colorectal adenocarcinoma cell line; used as intestinal epithelial model |
| HT-29 | Moderate | Colorectal adenocarcinoma cell line; lower expression than Caco-2 |
| HCT116 | Low | Colorectal carcinoma cell line; low endogenous expression |
| SW480 | Low | Colorectal adenocarcinoma cell line; low expression |
| HEK293 | Very low | Embryonic kidney cells; negligible expression, often used for transfection studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.559G>A (p.Val187Met) | Missense | Rare (found in CLD patients) | Impairs protein trafficking and function |
| c.2063C>T (p.Pro688Leu) | Missense | Rare (CLD) | Reduced anion exchange activity |
| c.951C>A (p.Tyr317Ter) | Nonsense | Rare (CLD) | Truncated protein, loss of function |
| c.1197_1198del (p.Val400GlyfsTer3) | Frameshift | Rare (CLD) | Premature stop codon, loss of function |
| c.2024+1G>A | Splice site | Rare (CLD) | Aberrant splicing, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most SLC26A3 mutations are loss-of-function, leading to congenital chloride diarrhea. These include missense, nonsense, frameshift, and splice-site variants that impair protein expression, trafficking, or anion exchange activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SLC26A3.
Dominant Negative (DN)
No dominant-negative effects have been described; CLD is inherited in an autosomal recessive manner, requiring biallelic loss-of-function mutations.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Transport of inorganic cations/anions and amino acids/oligopeptides (Reactome: R-HSA-425393)
• SLC-mediated transmembrane transport (Reactome: R-HSA-425407)
Protein Summary
The SLC26A3 protein (DRA) is a 764-amino acid transmembrane glycoprotein with 12-14 putative transmembrane domains. It functions as an electroneutral Cl-/HCO3- exchanger, coupling chloride absorption to bicarbonate secretion in the gut. DRA is localized to the apical membrane of intestinal epithelial cells, where it interacts with other ion transporters (e.g., CFTR, NHE3) to regulate fluid and electrolyte balance. The protein contains a STAS (sulfate transporter and anti-sigma factor antagonist) domain at the C-terminus, critical for protein stability and trafficking. Post-translational modifications, including glycosylation, are essential for proper function. DRA also plays a role in maintaining intracellular pH and is implicated in tumor suppression via regulation of cellular anion homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC26A3 Knockout HEK293 Cell Line | EDJ-KQ4476 | Human | 1811 | Details Get a Quote |
| SLC26A3 Knockout HeLa Cell Line | EDJ-KQ53112 | Human | 1811 | Details Get a Quote |
| SLC26A3 Knockout A-549 Cell Line | EDJ-KQ61585 | Human | 1811 | Details Get a Quote |
| SLC26A3 Knockout HCT 116 Cell Line | EDJ-KQ70075 | Human | 1811 | Details Get a Quote |
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