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SLC26A3
solute carrier family 26 member 3
SLC26A3 is located on the long (q) arm of chromosome 7, at band 7q22.3-q31.1. Arm ratio per GRCh38 - banding schematic.
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Overview
SLC26A3 belongs to the solute carrier family 26, a group of membrane transport proteins that facilitate the exchange of various anions across cell membranes. The protein encoded by this gene functions primarily as a chloride-bicarbonate exchanger, mediating the movement of these ions in opposite directions across the membrane of intestinal epithelial cells.
This transport activity is particularly important in the colon, where the protein helps regulate fluid absorption and maintain the appropriate ionic composition of intestinal contents. Disruption of SLC26A3 function can affect the balance of electrolytes and water in the digestive tract, with consequences for overall digestive health.
What the gene does
The SLC26A3 protein operates as an electroneutral anion exchanger, swapping chloride ions for bicarbonate ions across the apical membrane of intestinal epithelial cells. This exchange process is crucial for chloride absorption from the intestinal lumen into epithelial cells, whilst simultaneously secreting bicarbonate into the gut.
In the colon, this exchange mechanism contributes to the acidification of intestinal contents and helps drive water absorption, which is essential for the formation of normal stool consistency. The protein's activity is regulated by various factors, including intracellular pH and the concentration of transported ions themselves.
Beyond the intestine, SLC26A3 also appears to be expressed in other tissues, including the kidney and pancreas, though its role in these organs is less well characterised. The protein's function in maintaining acid-base balance extends beyond simple ion transport, as it influences the broader regulation of electrolyte homeostasis throughout the body.
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Chromosome location
The SLC26A3 gene is located on the long arm of chromosome 7, specifically within the region designated 7q22.3-q31.1. This chromosomal position places it amongst a cluster of genes involved in various transport and metabolic functions. The precise number of exons and detailed structural organisation of the gene have not been comprehensively documented in widely accessible genomic databases.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variants in SLC26A3 can alter the protein's ability to transport chloride and bicarbonate ions effectively. Such changes may affect the exchanger's stability, its localisation to the cell membrane, or its catalytic efficiency. The inheritance pattern for conditions associated with SLC26A3 variants can vary depending on the specific genetic context and the nature of the variants involved.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1039G>A | p.Ala347Thr | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital secretory diarrhea, chloride type |
c.1312-1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital secretory diarrhea, chloride type |
c.1514+1G>A | - | Pathogenic | ★★☆☆ | Congenital secretory diarrhea, chloride type |
c.1674del | p.Asp558fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital secretory diarrhea, chloride type |
c.1735C>T | p.Arg579Ter | Pathogenic | ★★☆☆ | Congenital secretory diarrhea, chloride type |
c.1750C>T | p.Gln584Ter | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.1954G>A | p.Asp652Asn | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital secretory diarrhea, chloride type |
c.-3_13del | p.Met1fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital secretory diarrhea, chloride type |
c.735+4_735+7del | - | Pathogenic | ★★☆☆ | Congenital secretory diarrhea, chloride type |
c.926_927del | p.Asp308_Phe309insTer | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital secretory diarrhea, chloride type |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in SLC26A3 have been associated with disruptions in intestinal electrolyte transport, which can manifest as digestive system abnormalities. Research suggests that loss of functional SLC26A3 activity interferes with normal chloride absorption and bicarbonate secretion in the colon, leading to alterations in fluid balance within the intestinal tract. The clinical presentation of SLC26A3-related conditions typically involves disturbances in bowel function and electrolyte homeostasis, though the severity and specific features can vary amongst affected individuals.
UK clinical status
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the SLC26A3 protein do?
The SLC26A3 protein functions as a chloride-bicarbonate exchanger in intestinal cells, swapping chloride ions for bicarbonate ions across cell membranes. This activity is essential for normal fluid absorption and electrolyte balance in the digestive tract.
Where in the body is SLC26A3 active?
SLC26A3 is primarily active in the intestinal tract, particularly in the colon, where it plays a key role in ion transport. The protein is also expressed at lower levels in other tissues, including the kidney and pancreas.
How are variants in SLC26A3 inherited?
The inheritance pattern for SLC26A3-related conditions can vary depending on the specific variants and clinical context. Individuals with questions about inheritance should discuss their family history with a healthcare provider or genetic counsellor.