Solute carrier family 26 member 6 · UniProt Q9BXS9
SLC26A6 (PAT1/CFEX) is a multifunctional apical-membrane anion exchanger that couples chloride transport to bicarbonate, oxalate, sulfate, hydroxide, and formate movement across epithelial and cardiac plasma membranes (PMID:12444019, PMID:15498800, PMID:20501439). Its cryo-EM structure adopts an inward-facing conformation with a central ion-binding site, and reconstitution in proteoliposomes establishes a 1:1 stoichiometry supporting electroneutral Cl-/HCO3- exchange and electrogenic Cl-/oxalate exchange (PMID:37351578). In the intestine SLC26A6 is the predominant transcellular secretory pathway for oxalate, acting in exchange for Cl- to limit body oxalate burden and prevent hyperoxaluria; loss of this pathway reverses net oxalate transport from secretion to absorption and impairs enteric oxalate excretion, including the compensatory excretion required in chronic kidney disease (PMID:16373425, PMID:22021714, PMID:32660969). In the kidney proximal tubule it mediates oxalate-stimulated NaCl absorption and the bulk of apical Cl-/base exchange (PMID:15574486), and across duodenal villi it is the major apical Cl-/HCO3- and SO4(2-)/HCO3- exchanger (PMID:17170027). In the heart it serves as the predominant Cl-/HCO3- and Cl-/OH- exchanger acting as an acid loader, and its ablation protects against ischemia/reperfusion injury by raising intracellular pH (PMID:15498800, PMID:23933580, PMID:41462888). Transport is functionally coupled to NHE3 in electroneutral NaCl absorption (PMID:17763866), to CFTR in secretagogue-specific HCO3- secretion (PMID:16472591, PMID:20969732), and to carbonic anhydrase II (PMID:20150244), while its STAS domain physically interacts with NaDC-1 to reciprocally regulate citrate handling (PMID:23833257). Activity requires N-glycosylation at two extracellular-loop sites (PMID:27681177) and is negatively regulated by PKC-delta-driven membrane internalization and alpha-adrenergic signaling (PMID:15498800, PMID:17151144). Human dominant-negative missense mutations (e.g. R507W) reduce oxalate transport and surface expression and cosegregate with enteric hyperoxaluria and nephrolithiasis (PMID:35115415).
Established where SLC26A6 acts by placing the protein at the luminal surface of secretory epithelia, framing it as a candidate apical anion exchanger.
Evidence Immunohistochemistry on pancreatic ductal cell lines
Demonstrated that SLC26A6 and its splice variants are functional anion transporters with intracellular N- and C-termini, and that the C-terminal TRL motif binds NHERF/E3KARP PDZ domains, linking the transporter to scaffolding machinery.
Evidence Functional expression and topology mapping in Xenopus oocytes; in vitro PDZ binding with truncation mutagenesis
Knockout mice defined SLC26A6's native physiological roles, identifying it as the mediator of oxalate-stimulated NaCl absorption and a major Cl-/base exchanger in proximal tubule and duodenum, and as the predominant cardiac Cl-/HCO3- and Cl-/OH- exchanger inhibited by alpha-adrenergic/PKC signaling.
Evidence Slc26a6-null mice with proximal tubule microperfusion, duodenal Ussing chambers, and cardiac pHi measurements with pharmacological modulation
Quantified SLC26A6's contribution to intestinal oxalate secretion, showing that its loss reverses net oxalate flux from secretion to absorption in the distal ileum.
Evidence Ussing chamber radiotracer flux in Slc26a6-null mice with DIDS inhibition
Defined the relative and directional roles of SLC26A6 in duodenal and pancreatic anion transport and resolved the PKC-delta downregulation mechanism, establishing distinct CFTR-dependent and -independent secretagogue pathways.
Evidence Comparative KO panels (PAT-1, DRA, AE4, CFTR), Ussing chamber and BCECF readouts, surface biotinylation, and PKC-delta inhibition assays
PMID:16472591 PMID:16901991 PMID:17151144 PMID:17170027
Established functional coupling between SLC26A6 and NHE3 in electroneutral NaCl absorption in jejunum and proximal tubule, showing loss of SLC26A6 reduces NHE3 activity without changing its abundance.
Evidence Slc26a6-/- and NHE3-/- mice; isotopic flux measurements and proximal tubule microperfusion with pH measurements
Revealed species-specific transport kinetics and electrogenicity governed by both transmembrane and cytoplasmic domains, and identified a hypofunctional human variant, opening the question of SLC26A6 contribution to human hyperoxaluria.
Evidence Xenopus oocyte expression, electrophysiology, human-mouse chimeras, and variant transport assays
Identified transcriptional control of SLC26A6 by IFN-gamma via an IRF-1/ISRE element, connecting inflammatory signaling to anion transport capacity.
Evidence Promoter-luciferase reporters, deletion and ISRE mutagenesis, and IFN-gamma treatment of Caco-2 cells
Confirmed in a human intestinal epithelial model that SLC26A6 mediates a major fraction of apical oxalate, Cl-, and HCO3- exchange, with vectorial transport driven by counterion gradients.
Evidence siRNA knockdown in Caco-2BBe1 monolayers with radiotracer flux, Ussing chamber, and BCECF assays
Showed membrane-potential and CFTR-dependent modulation of SLC26A6 Cl-/HCO3- exchange and its functional interaction with carbonic anhydrase II during nutrient absorption, integrating it into epithelial pH homeostasis.
Evidence Multiple KO models (Pat-1, DRA, CFTR, CAII), BCECF fluorometry, and Ussing chamber Isc measurements
Cleanly separated transcellular SLC26A6-mediated secretory oxalate flux from paracellular absorptive flux, defining SLC26A6 as the saturable transcellular secretory route.
Evidence Dual-tracer oxalate/mannitol flux in Slc26a6-null mice with DIDS and saturation analysis
Identified the STAS domain-NaDC-1 interaction as a node linking SLC26A6 to citrate homeostasis, and confirmed cardiac SLC26A6 as an electrogenic Cl-/HCO3- and Cl-/oxalate exchanger by direct electrophysiology.
Evidence Oocyte co-expression, reciprocal pulldown, STAS mutagenesis, null mice, and patch-clamp in cardiomyocytes
Established that N-glycosylation at two extracellular-loop sites is required for transport activity and influences trafficking efficiency, defining a post-translational determinant of function.
Evidence Glycosylation-site mutagenesis, enzymatic deglycosylation, surface biotinylation, and oxalate transport assays
Extended SLC26A6's substrate repertoire to intestinal sulfate efflux, showing it limits net sulfate absorption.
Evidence 35SO4 and 36Cl- flux in Slc26a6 and Slc26a3 KO mice with urinary sulfate measurements
Showed tissue-specific substrate selectivity, with salivary acinar SLC26A6 mediating Cl-/oxalate but not HCO3- secretion.
Evidence Slc26a6 KO mice, immunolocalization, heterologous expression, and salivary oxalate/HCO3- measurements
Defined SLC26A6's contribution to pancreatic acinar fluid/HCO3- secretion and identified miR-125a-5p as a post-transcriptional repressor, adding a non-coding regulatory layer.
Evidence Slc26a6 KO pancreas secretion assays; 3'-UTR luciferase reporter and miRNA mimic in Caco-2 cells
Established the physiological importance of enteric SLC26A6 secretion in chronic kidney disease and the dominant-negative impact of STAS-domain disease variants on trafficking and citrate regulation.
Evidence Slc26a6 KO in two CKD models with fecal/plasma oxalate; STAS-variant surface expression and SLC13 co-transport assays
Provided a selective small-molecule inhibitor that confirmed SLC26A6 as the predominant anion exchanger driving fluid absorption in the ileum, separable from DRA.
Evidence High-throughput screen yielding PAT1inh-B01; halide-sensing assay; in vivo intestinal loop experiments
Provided direct human genetic evidence linking SLC26A6 to disease, with a dominant-negative R507W mutation cosegregating with enteric hyperoxaluria and nephrolithiasis.
Evidence Whole-exome sequencing with family cosegregation; transport, surface expression, and co-transfection dominant-negative assays
Resolved the molecular mechanism of anion exchange by solving the inward-facing cryo-EM structure and reconstituting transport, establishing 1:1 stoichiometry and the structural basis of altered anion selectivity versus SLC26A9.
Evidence Cryo-EM structure determination, proteoliposome reconstitution, and functional transport assays
Revealed a microbiome-dependent role for SLC26A6 in maintaining the gut barrier, with its loss reducing butyrate-producing microbes and increasing colitis susceptibility transferable by co-housing.
Evidence PAT1 KO mice, DSS colitis, 16S sequencing, metabolomics, tight-junction analysis, and co-housing experiment
Showed that cardiac SLC26A6 ablation protects against ischemia/reperfusion injury by raising intracellular pH and improving contractile and Ca2+ handling, identifying it as a detrimental acid loader in the ischemic heart.
Evidence Slc26a6 KO mice in an I/R model with echocardiography, hemodynamics, pHi imaging, and cardiomyocyte sarcomere/Ca2+ measurements
Identified a CaSR-PKA-FOXO4 axis that transcriptionally upregulates SLC26A6 and promotes calcium oxalate crystal formation, connecting calcium-sensing signaling to stone risk.
Evidence Rat calcium oxalate stone model and NRK-52E cells with agonists/inhibitors; SLC26A6 promoter dual-luciferase reporter assay
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 2000 | SLC26A6 protein localizes to the apical surface of pancreatic ductal cells, as determined by immunohistochemistry, suggesting a role as a luminal anion exchanger. | Immunohistochemistry on pancreatic ductal cell lines (Capan-1 and Capan-2) | Genomics | Medium | 11087667 |
| 2002 | SLC26A6 and its splice variants SLC26A6c and SLC26A6d function as anion transporters mediating Cl- and SO4(2-) transport when expressed in Xenopus oocytes; transport is inhibited by DIDS and HCO3-. The NH2- and COOH-terminal tails are intracellular, consistent with an even number of transmembrane domains. | Functional expression in Xenopus oocytes; immunofluorescence for topology | American journal of physiology. Cell physiology | High | 12444019 |
| 2002 | The COOH-terminus of SLC26A6 binds to the first and second PDZ domains of E3KARP (NHE3 kinase A regulatory protein) and NHERF proteins in vitro; truncation of the last three amino acids (TRL) abolishes this interaction without affecting transport function. | In vitro PDZ domain binding assay; truncation mutagenesis | American journal of physiology. Cell physiology | Medium | 12444019 |
| 2004 | Slc26a6-null mice show abolished oxalate-stimulated NaCl absorption in kidney proximal tubules and a 58% decrease in apical membrane Cl-/base exchange activity, establishing Slc26a6 as the mediator of oxalate-stimulated NaCl transport and a major contributor to proximal tubule Cl-/base exchange. | Gene knockout mice; in vitro microperfusion of proximal tubules; pH-sensitive dye BCPCF | American journal of physiology. Cell physiology | High | 15574486 |
| 2004 | Slc26a6 deletion reduces baseline HCO3- secretion (~30%) in the duodenum, as measured in Ussing chambers, but does not affect forskolin-stimulated HCO3- secretion. | Slc26a6 knockout mice; Ussing chamber HCO3- secretion measurements | American journal of physiology. Cell physiology | High | 15574486 |
| 2004 | Slc26a6 (SLC26A6) functions as a Cl-/HCO3- exchanger and Cl-/OH- exchanger in the heart; it is the predominant Cl-/HCO3- and Cl-/OH- exchanger in mouse ventricular myocytes. Alpha-adrenergic receptor activation (via PKC) inhibits SLC26A6 Cl-/HCO3- exchange activity. | Quantitative RT-PCR; immunohistochemistry; intracellular pH fluorescence measurements (BCECF) in HEK293 cells transfected with SLC26A6; pharmacological stimulation with alpha-adrenergic agonists | The Journal of physiology | High | 15498800 |
| 2005 | PAT1 (Slc26a6) mediates a significant fraction of oxalate efflux (secretion) across the apical membrane of the distal ileum in exchange for Cl-, as demonstrated by the reversal of net oxalate transport from secretion to absorption in Slc26a6-null mice and DIDS sensitivity. | Slc26a6 knockout mice; Ussing chamber radiotracer flux measurements; pharmacological inhibition with DIDS | American journal of physiology. Gastrointestinal and liver physiology | High | 16373425 |
| 2006 | PAT-1 (Slc26a6) is the predominant contributor (65-80%) to basal Cl-/HCO3- exchange and the sole mediator of SO4(2-)/HCO3- exchange across the apical membrane of the upper villous epithelium of the murine duodenum. | Gene-targeted deletion mice (PAT-1-, DRA-, AE4-); pH-sensitive dye BCECF fluorescence in intact duodenal mucosa | American journal of physiology. Gastrointestinal and liver physiology | High | 17170027 |
| 2006 | SLC26A6-mediated PGE2-stimulated duodenal HCO3- secretion is CFTR-independent, whereas forskolin-stimulated HCO3- secretion is completely SLC26A6-independent and CFTR-dependent, establishing distinct transport pathways for different secretagogues. | SLC26A6-/- and CFTR-/- mouse duodenal mucosa in Ussing chambers; pharmacological stimulation with PGE2, forskolin, and carbachol | Gastroenterology | High | 16472591 |
| 2006 | PKC-delta activation inhibits multiple modes of Slc26a6-mediated anion exchange (Cl/formate, Cl/oxalate, Cl/Cl) and causes redistribution of Slc26a6 from the plasma membrane to an intracellular compartment, reducing surface-biotinylation-accessible protein. | Functional expression in Xenopus oocytes; surface biotinylation; immunofluorescence microscopy; PKC-delta-selective inhibitor rottlerin; PMA stimulation; mouse duodenal oxalate secretion assay | American journal of physiology. Cell physiology | High | 17151144 |
| 2006 | Slc26a6 deletion in pancreatic ducts shows HCO3- efflux is mediated by Slc26a6 (HCO3-efflux mode decreased in null mice), while HCO3-influx mode is upregulated in null mice. Compensatory >5-fold upregulation of Slc26a3 (DRA) expression occurs in Slc26a6 knockout pancreas. | Slc26a6 knockout mice; pH-sensitive dye BCECF in microperfused interlobular pancreatic ducts; semiquantitative RT-PCR | American journal of physiology. Gastrointestinal and liver physiology | High | 16901991 |
| 2007 | Slc26a6 acts in concert with NHE3 in electroneutral NaCl absorption in the small intestinal jejunum; net Cl- and Na+ fluxes are significantly reduced in Slc26a6-/- animals, and Slc26a6 also mediates Cl- absorption during glucose-driven salt absorption. | Slc26a6-/- and NHE3-/- knockout mice; Ussing chambers with 36Cl- and 22Na+ flux measurements; NHE3 immunofluorescence and immunoblot | Pflugers Archiv : European journal of physiology | High | 17763866 |
| 2007 | Slc26a6 deletion reduces apical Na+/H+ exchanger (NHE3) activity in the straight segment (S3) of the kidney proximal tubule, decreasing intracellular pH and blunting formate-induced alkalinization, without affecting NHE3 protein abundance or distribution. | In vitro microperfusion of proximal tubule S3 segments; BCPCF-AM pH measurements; immunoblotting and immunofluorescence for NHE3 | American journal of nephrology | Medium | 18046080 |
| 2008 | Human SLC26A6 mediates oxalate/Cl- exchange with different kinetics than mouse Slc26a6: human SLC26A6 has a K1/2 for extracellular Cl- of ~62 mM (vs. 8 mM for mouse), and human SLC26A6-mediated oxalate transport appears electroneutral whereas mouse Slc26a6 mediates electrogenic oxalate/Cl- exchange. These differences are determined by both transmembrane and C-terminal cytoplasmic domains. | Heterologous expression in Xenopus oocytes; isotopic flux assays; electrophysiology; human-mouse chimera studies | The Journal of physiology | High | 18174209 |
| 2008 | The SLC26A6 variant V206M (p.Val206Met) shows ~30% reduction in oxalate transport activity when expressed in Xenopus oocytes, though heterozygosity for this variant does not measurably affect plasma or urine oxalate in hyperoxaluria patients. | Functional expression of SLC26A6 variants in Xenopus laevis oocytes; oxalate transport assay | American journal of kidney diseases | Medium | 18951670 |
| 2008 | The SLC26A6 promoter region -214/-44 harbors cis-acting elements required for maximal promoter activity; IFN-gamma decreases SLC26A6 mRNA, function, and promoter activity via an IRF-1 binding site (ISRE) located at -318/-300 bp, and mutation of this ISRE abrogates IFN-gamma inhibition. | Promoter-luciferase reporter assays; deletion analysis; site-directed mutagenesis of ISRE; IFN-gamma treatment of Caco-2 cells | Journal of cellular biochemistry | Medium | 18655181 |
| 2009 | PAT-1 (SLC26A6) at the apical membrane of Caco-2BBe1 cells mediates oxalate, Cl-, and HCO3- exchange; siRNA knockdown reduces PAT-1 protein >60% and decreases unidirectional oxalate fluxes ~50%, Cl- fluxes ~35%, and Cl-/HCO3- exchange ~50%. PAT-1-mediated oxalate exchange is inhibited by mucosal DIDS (EC50 ~5 µM) and by mucosal Cl- (EC50 <20 mM). Vectorial oxalate transport depends principally on counterion gradients. | siRNA knockdown in Caco-2BBe1 monolayers; radiotracer flux measurements; Ussing chambers; BCECF fluorometry | American journal of physiology. Gastrointestinal and liver physiology | High | 20501439 |
| 2010 | Pat-1 (Slc26a6) contributes to Cl-/HCO3- exchange in the lower villus epithelium; its activity is masked during glucose absorption due to membrane depolarization, but is active during electroneutral mannose absorption. Pat-1-dependent Cl-/HCO3- exchange activity is inhibited by membrane depolarization only when CFTR is co-expressed. | Pat-1 KO, DRA KO, CFTR KO, and DRA/CFTR double-KO mice; BCECF fluorometry; Ussing chamber Isc measurements | Acta physiologica (Oxford, England) | High | 20969732 |
| 2010 | Pat-1 (Slc26a6) Cl-/HCO3- exchange contributes to intracellular pH regulation in villous epithelium during H+-dipeptide absorption via Pept1. This involves interaction with carbonic anhydrase II (CAII), and both Pat-1 and CAII are required for increased Cl-(OUT)/HCO3-(IN) exchange during glycyl-sarcosine exposure. | Pat-1 KO and CAII KO mice; Ussing chambers; BCECF microfluorometry; pharmacological inhibitors of Cl-/HCO3- exchange and carbonic anhydrase | American journal of physiology. Gastrointestinal and liver physiology | High | 20150244 |
| 2011 | SLC26A6-dependent transcellular oxalate secretion in the duodenum is saturable and DIDS-sensitive, whereas absorptive oxalate flux occurs through the paracellular 'leak' pathway (passive, non-saturable, parallels mannitol). In Slc26a6-null mice, secretory flux of oxalate is equivalent to paracellular mannitol flux, confirming SLC26A6 as the transcellular secretory pathway. | Slc26a6 knockout mice; simultaneous [14C]oxalate and [3H]mannitol flux measurements; DIDS inhibition; saturation analysis | Journal of the American Society of Nephrology : JASN | High | 22021714 |
| 2012 | SLC26A3, SLC26A6, and SLC9A3R1 are expressed in mouse sperm midpiece and interact with each other and with CFTR, as demonstrated by RT-PCR, immunocytochemistry, Western blot, and immunoprecipitation. SLC26A3 and CFTR are involved in the Cl- increase induced by db-cAMP during capacitation. | RT-PCR; immunocytochemistry; Western blot; co-immunoprecipitation from mouse sperm | Biology of reproduction | Medium | 21976599 |
| 2013 | The STAS domain of Slc26a6 physically interacts with the first intracellular loop of NaDC-1, and this interaction has functional consequences: NaDC-1 enhances Slc26a6 transport activity when co-expressed in Xenopus oocytes, while Slc26a6 inhibits NaDC-1 citrate transport in an activity-dependent manner. Slc26a6-null mice show increased NaDC-1-mediated succinate uptake, hyperoxaluria, and hypocitraturia. | Co-expression in Xenopus oocytes; biochemical pulldown/co-IP; Slc26a6-null mice; in vitro succinate uptake assays; STAS domain mutagenesis | Journal of the American Society of Nephrology : JASN | High | 23833257 |
| 2013 | Cardiac Slc26a6 functions as an electrogenic Cl-/HCO3- and Cl-/oxalate exchanger in cardiomyocytes, as directly demonstrated by patch-clamp recordings. Four cardiac isoforms (C-a, C-b, C-c, C-d) are expressed in both atrial and ventricular myocytes at the plasma membrane. | RT-PCR; immunofluorescence confocal microscopy; patch-clamp electrophysiology with fast solution exchange in cardiomyocytes | Cardiovascular research | High | 23933580 |
| 2016 | N-glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically required for Cl--dependent oxalate transport activity. Glycosylation is not essential for cell-surface delivery but affects the efficacy of plasma membrane trafficking. Enzymatic deglycosylation of surface-expressed SLC26A6 strongly reduces oxalate transport. | Enzymatic deglycosylation; N-glycosylation site mutagenesis; surface biotinylation; functional oxalate transport assays in transfected cells | American journal of physiology. Cell physiology | High | 27681177 |
| 2017 | PAT1 (Slc26a6) contributes to sulfate efflux across the apical membrane of the distal ileum; PAT1-KO mice show increased urinary sulfate excretion 1.8-fold, indicating that PAT1-mediated secretion reduces net intestinal sulfate absorption. | Slc26a6 and Slc26a3 knockout mice; 35SO4 and 36Cl- transepithelial flux measurements in Ussing chambers; urine and plasma sulfate measurements | American journal of physiology. Gastrointestinal and liver physiology | Medium | 28526688 |
| 2018 | Slc26a6 localizes to the apical membrane of submandibular salivary gland acinar cells (not ducts) and mediates Cl-/oxalate exchange in these cells. Slc26a6-/- mice show significantly reduced Cl-/oxalate exchange and reduced oxalate secretion in submandibular saliva, but HCO3- secretion is unaffected. | Slc26a6 knockout mice; RNA-seq and Western blot; immunolocalization; CHO-K1 cell transfection and functional assay; salivary oxalate and HCO3- measurements | The Journal of biological chemistry | High | 29530983 |
| 2019 | Slc26a6 localizes primarily to the apical membrane of pancreatic exocrine acinar cells and mediates the HCO3--dependent component of fluid secretion (~35% of total fluid secretion); Slc26a6-null mice show ~35% reduction in stimulated pancreatic juice volume and HCO3- secretion. | Slc26a6 knockout mice; ex vivo pancreas secretion assay; immunolocalization | American journal of physiology. Cell physiology | Medium | 31532720 |
| 2019 | miR-125a-5p negatively regulates SLC26A6 (PAT-1) expression by binding to the 3'-UTR of PAT-1 mRNA; transfection of miR-125a-5p mimic in Caco-2 cells decreased both PAT-1 mRNA and protein levels. | Dual luciferase reporter assay with 3'-UTR cloning; miRNA mimic transfection in intestinal epithelial cell lines; RT-PCR and Western blot | American journal of physiology. Cell physiology | Medium | 31042422 |
| 2020 | Slc26a6-mediated enteric oxalate secretion is critical for decreasing body burden of oxalate in chronic kidney disease (CKD): Slc26a6-null mice with CKD fail to increase fecal oxalate excretion and show elevated plasma oxalate. Intestinal Slc26a6 mRNA and protein are greatly increased in CKD mice, and this upregulation is driven by CKD-associated changes rather than elevated plasma oxalate per se. | Slc26a6 knockout mice with CKD models (high oxalate diet or aristolochic acid); qPCR, immunohistochemistry, Western blot for intestinal Slc26a6; fecal and plasma oxalate measurements | Journal of the American Society of Nephrology : JASN | High | 32660969 |
| 2020 | STAS domain mutations of SLC26A6 (homolog of D23H/D673N and R621G) abolish or reduce SLC26A6 expression and membrane trafficking and impair regulation of SLC13-mediated citrate transport; cotransfection experiments in vitro confirm dominant-negative effects of D673N on wild-type SLC26A6. | In vitro expression of SLC26A6 STAS domain variants; surface expression assays; citrate transport functional assays with SLC13 co-expression | Frontiers in pharmacology | Medium | 32317970 |
| 2021 | SLC26A6 (PAT1inh-B01) selective inhibitor (pyrazolo-pyrido-pyrimidinone, IC50 ~350 nM) fully inhibits PAT1-mediated anion exchange without inhibiting SLC26A3 (DRA). In vivo, PAT1inh-B01 inhibits fluid absorption by ~50% in midjejunal loops and >80% in ileal loops in mice, establishing PAT1 as the predominant anion exchanger for fluid absorption in the ileum. | High-throughput small-molecule screen; halide-sensing fluorescent protein assay; in vivo intestinal loop experiments in mice; co-administration with DRA inhibitor | JCI insight | High | 34100381 |
| 2022 | A rare heterozygous missense mutation R507W in SLC26A6 causes dominant-negative reduction of Cl--dependent oxalate transport by reducing both transport activity and membrane surface expression. Co-transfection of R507W with wild-type SLC26A6 demonstrates strong dominant-negative suppression of wild-type protein, cosegregating with enteric hyperoxaluria and nephrolithiasis in the family. | Cell culture transfection; Cl--dependent oxalate transport assay; surface expression analysis; cotransfection dominant-negative assay; whole-exome sequencing | Journal of medical genetics | High | 35115415 |
| 2023 | Cryo-EM structure of human SLC26A6 defines an inward-facing conformation. The ion-binding site is located in the center of a mobile unit of the membrane-inserted domain. Structure-function reconstitution in proteoliposomes establishes 1:1 stoichiometry, electroneutral Cl-/HCO3- exchange, and electrogenic Cl-/oxalate exchange. The remodeled ion-binding site (vs. SLC26A9) explains altered anion selectivity and coupling mechanism. | Cryo-electron microscopy structure determination; reconstitution in proteoliposomes; functional transport assays; comparison with SLC26A9 structure | eLife | High | 37351578 |
| 2024 | Loss of PAT1 (SLC26A6) in PKO mice disrupts gut microbiome composition, reduces butyrate and butyrate-producing microbes, decreases tight junction protein expression, and increases susceptibility to DSS-induced colitis. Co-housing WT with PKO mice transfers PKO-like tight junction signatures to WT mice, indicating that the gut barrier defect is linked to microbiome changes. | PAT1 knockout mice; DSS colitis model; 16S rRNA sequencing; mass spectrometry metabolomics; Western blot and RT-PCR for tight junction proteins; co-housing experiment; cytokine measurements; H&E staining | Gastroenterology | High | 38735402 |
| 2025 | Ablation of Slc26a6 protects the mouse heart from ischemia/reperfusion (I/R) injury: Slc26a6-null mice show lower troponin I, better systolic/diastolic function, reduced infarct size, and elevated intracellular pH (pHi) in the heart. Cardiomyocytes from the infarct zone of Slc26a6-null mice show better sarcomere shortening, Ca2+ transients, and sarcoplasmic reticulum Ca2+ load. | Slc26a6 knockout mice; I/R model; echocardiography; hemodynamic monitoring; fluorescence microscopy for pHi; histochemistry; cellular sarcomere shortening and Ca2+ transient measurements | Biomedicines | High | 41462888 |
| 2026 | CaSR activation promotes PKA-mediated phosphorylation of FOXO4, which transcriptionally upregulates SLC26A6 expression in renal tubular epithelial cells. FOXO4 directly regulates the SLC26A6 promoter, as confirmed by dual-luciferase reporter assay. Inhibition of CaSR, PKA, or FOXO4 reduces SLC26A6 expression and crystal formation in a rat calcium oxalate stone model. | Rat calcium oxalate stone model; NRK-52E cell line with agonists/inhibitors; Western blot; immunohistochemistry; RT-qPCR; dual-luciferase reporter assay for SLC26A6 promoter | Frontiers in cell and developmental biology | Medium | 41938536 |
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2000 | Mapping of five new putative anion transporter genes in human and characterization of SLC26A6, a candidate gene for pancreatic anion exchanger. | Genomics | 163 | 11087667 |
| 2004 | Renal and intestinal transport defects in Slc26a6-null mice. | American journal of physiology. Cell physiology | 148 | 15574486 |
| 2005 | Ileal oxalate absorption and urinary oxalate excretion are enhanced in Slc26a6 null mice. | American journal of physiology. Gastrointestinal and liver physiology | 146 | 16373425 |
| 2002 | Isoforms of SLC26A6 mediate anion transport and have functional PDZ interaction domains. | American journal of physiology. Cell physiology | 106 | 12444019 |
| 2006 | PAT-1 (Slc26a6) is the predominant apical membrane Cl-/HCO3- exchanger in the upper villous epithelium of the murine duodenum. | American journal of physiology. Gastrointestinal and liver physiology | 84 | 17170027 |
| 2006 | Involvement of the anion exchanger SLC26A6 in prostaglandin E2- but not forskolin-stimulated duodenal HCO3- secretion. | Gastroenterology | 75 | 16472591 |
| 2001 | Cloning and characterization of SLC26A6, a novel member of the solute carrier 26 gene family. | Genomics | 73 | 11247665 |
| 2011 | Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion. | Journal of the American Society of Nephrology : JASN | 72 | 22021714 |
| 2012 | Participation of the Cl-/HCO(3)- exchangers SLC26A3 and SLC26A6, the Cl- channel CFTR, and the regulatory factor SLC9A3R1 in mouse sperm capacitation. | Biology of reproduction | 69 | 21976599 |
| 2008 | Species differences in Cl- affinity and in electrogenicity of SLC26A6-mediated oxalate/Cl- exchange correlate with the distinct human and mouse susceptibilities to nephrolithiasis. | The Journal of physiology | 61 | 18174209 |
| 2004 | Slc26a6: a cardiac chloride-hydroxyl exchanger and predominant chloride-bicarbonate exchanger of the mouse heart. | The Journal of physiology | 61 | 15498800 |
| 2013 | SLC26A6 and NaDC-1 transporters interact to regulate oxalate and citrate homeostasis. | Journal of the American Society of Nephrology : JASN | 60 | 23833257 |
| 2006 | Effect of Slc26a6 deletion on apical Cl-/HCO3- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct. | American journal of physiology. Gastrointestinal and liver physiology | 56 | 16901991 |
| 2007 | Sodium and chloride absorptive defects in the small intestine in Slc26a6 null mice. | Pflugers Archiv : European journal of physiology | 53 | 17763866 |
| 2008 | Phenotypic and functional analysis of human SLC26A6 variants in patients with familial hyperoxaluria and calcium oxalate nephrolithiasis. | American journal of kidney diseases : the official journal of the National Kidney Foundation | 44 | 18951670 |
| 2021 | Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6. | mSystems | 38 | 34783577 |
| 2006 | Regulation of anion exchanger Slc26a6 by protein kinase C. | American journal of physiology. Cell physiology | 38 | 17151144 |
| 2009 | Parsing apical oxalate exchange in Caco-2BBe1 monolayers: siRNA knockdown of SLC26A6 reveals the role and properties of PAT-1. | American journal of physiology. Gastrointestinal and liver physiology | 28 | 20501439 |
| 2015 | Sulfate and thiosulfate inhibit oxalate transport via a dPrestin (Slc26a6)-dependent mechanism in an insect model of calcium oxalate nephrolithiasis. | American journal of physiology. Renal physiology | 27 | 26538444 |
| 2013 | In-vivo functional study on the involvement of CFTR, SLC26A6, NHE-1 and CA isoenzymes II and XII in uterine fluid pH, volume and electrolyte regulation in rats under different sex-steroid influence. | International journal of medical sciences | 27 | 23869188 |
| 2014 | Mechanisms of Cl(-) uptake in rainbow trout: cloning and expression of slc26a6, a prospective Cl(-)/HCO3(-) exchanger. | Comparative biochemistry and physiology. Part A, Molecular & integrative physiology | 24 | 25446148 |
| 2018 | The apical anion exchanger Slc26a6 promotes oxalate secretion by murine submandibular gland acinar cells. | The Journal of biological chemistry | 23 | 29530983 |
| 2015 | Slc26a3/Dra and Slc26a6 in Murine Ameloblasts. | Journal of dental research | 22 | 26394631 |
| 2018 | High expression of SLC26A6 in the kidney may contribute to renal calcification via an SLC26A6-dependent mechanism. | PeerJ | 20 | 30002986 |
| 2016 | In Silico Screening and Molecular Dynamic Study of Nonsynonymous Single Nucleotide Polymorphisms Associated with Kidney Stones in the SLC26A6 Gene. | The Journal of urology | 20 | 26812303 |
| 2012 | Urinary metabolic phenotyping the slc26a6 (chloride-oxalate exchanger) null mouse model. | Journal of proteome research | 20 | 22594923 |
| 2012 | Progesterone downregulates oestrogen-induced expression of CFTR and SLC26A6 proteins and mRNA in rats' uteri. | Journal of biomedicine & biotechnology | 20 | 23226939 |
| 2005 | SLC26A6 and SLC26A7 anion exchangers have a distinct distribution in human kidney. | Nephron. Experimental nephrology | 20 | 15956810 |
| 2010 | Functional activity of Pat-1 (Slc26a6) Cl(−)/HCO₃(−) exchange in the lower villus epithelium of murine duodenum. | Acta physiologica (Oxford, England) | 19 | 20969732 |
| 2017 | Loss of the anion exchanger DRA (Slc26a3), or PAT1 (Slc26a6), alters sulfate transport by the distal ileum and overall sulfate homeostasis. | American journal of physiology. Gastrointestinal and liver physiology | 18 | 28526688 |
| 2010 | Putative anion transporter-1 (Pat-1, Slc26a6) contributes to intracellular pH regulation during H+-dipeptide transport in duodenal villous epithelium. | American journal of physiology. Gastrointestinal and liver physiology | 18 | 20150244 |
| 2020 | Enteric Oxalate Secretion Mediated by Slc26a6 Defends against Hyperoxalemia in Murine Models of Chronic Kidney Disease. | Journal of the American Society of Nephrology : JASN | 17 | 32660969 |
| 2018 | Helicobacter pylori infection downregulates duodenal CFTR and SLC26A6 expressions through TGFβ signaling pathway. | BMC microbiology | 17 | 30119655 |
| 2016 | The role of the rectum in osmoregulation and the potential effect of renoguanylin on SLC26a6 transport activity in the Gulf toadfish (Opsanus beta). | American journal of physiology. Regulatory, integrative and comparative physiology | 17 | 27030664 |
| 2008 | Analysis of the 206M polymorphic variant of the SLC26A6 gene encoding a Cl- oxalate transporter in patients with primary hyperparathyroidism. | European journal of endocrinology | 17 | 19029225 |
| 2014 | Genistein induces increase in fluid pH, Na+ and HCO3(-) concentration, SLC26A6 and SLC4A4 (NBCe1)-B expression in the uteri of ovariectomized rats. | International journal of molecular sciences | 16 | 24434640 |
| 2024 | A Direct Link Implicating Loss of SLC26A6 to Gut Microbial Dysbiosis, Compromised Barrier Integrity, and Inflammation. | Gastroenterology | 15 | 38735402 |
| 2022 | Dominant negative mutation in oxalate transporter SLC26A6 associated with enteric hyperoxaluria and nephrolithiasis. | Journal of medical genetics | 15 | 35115415 |
| 2016 | N-glycosylation critically regulates function of oxalate transporter SLC26A6. | American journal of physiology. Cell physiology | 15 | 27681177 |
| 2008 | Characterization of the 5'-flanking region and regulation of expression of human anion exchanger SLC26A6. | Journal of cellular biochemistry | 14 | 18655181 |
| 2021 | SLC26A6-selective inhibitor identified in a small-molecule screen blocks fluid absorption in small intestine. | JCI insight | 13 | 34100381 |
| 2013 | Slc26a6 functions as an electrogenic Cl-/HCO3- exchanger in cardiac myocytes. | Cardiovascular research | 13 | 23933580 |
| 2023 | Structural and functional properties of the transporter SLC26A6 reveal mechanism of coupled anion exchange. | eLife | 12 | 37351578 |
| 2007 | Slc26a6 (PAT1) deletion downregulates the apical Na+/H+ exchanger in the straight segment of the proximal tubule. | American journal of nephrology | 12 | 18046080 |
| 2020 | Novel Human Polymorphisms Define a Key Role for the SLC26A6-STAS Domain in Protection From Ca2+-Oxalate Lithogenesis. | Frontiers in pharmacology | 11 | 32317970 |
| 2019 | miR-125a-5p: a novel regulator of SLC26A6 expression in intestinal epithelial cells. | American journal of physiology. Cell physiology | 11 | 31042422 |
| 2016 | Involvement of Cl(-)/HCO3(-) exchanger SLC26A3 and SLC26A6 in preimplantation embryo cleavage. | Scientific reports | 11 | 27346053 |
| 2022 | Estrogen treatment reduced oxalate transporting activity and enhanced migration through the involvement of SLC26A6 in lung cancer cells. | Toxicology in vitro : an international journal published in association with BIBRA | 10 | 35500753 |
| 2021 | Systemic characterization of the SLC family genes reveals SLC26A6 as a novel oncogene in hepatocellular carcinoma. | Translational cancer research | 9 | 35116598 |
| 2018 | Sex-independent expression of chloride/formate exchanger Cfex (Slc26a6) in rat pancreas, small intestine, and liver, and male-dominant expression in kidneys. | Arhiv za higijenu rada i toksikologiju | 9 | 30864378 |
| 2015 | Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis. | Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] | 9 | 26372434 |
| 2006 | Anion exchangers in flux: functional differences between human and mouse SLC26A6 polypeptides. | Novartis Foundation symposium | 9 | 17120764 |
| 2019 | Enhanced Activity by NKCC1 and Slc26a6 Mediates Acidic pH and Cl- Movement after Cardioplegia-Induced Arrest of db/db Diabetic Heart. | Mediators of inflammation | 7 | 31582903 |
| 2021 | SLC26A6 and NADC‑1: Future direction of nephrolithiasis and calculus‑related hypertension research (Review). | Molecular medicine reports | 5 | 34458928 |
| 2015 | Bicarbonate exchangers SLC26A3 and SLC26A6 are localized at the apical membrane of porcine vas deferens epithelium. | Physiological reports | 5 | 25907791 |
| 2019 | Slc26a6 is an apical membrane anion exchanger that drives HCO3--dependent fluid secretion in murine pancreatic acinar cells. | American journal of physiology. Cell physiology | 4 | 31532720 |
| 2019 | Novel SLC26A6 gene polymorphism rs184187143 is associated with diabetic ketoacidosis of gestational diabetes. | European review for medical and pharmacological sciences | 4 | 31539142 |
| 2025 | The enigmatic SLC26A6 multifunctional anion transporter: recent advances in structure-function relationship, pathophysiological significance and novel pharmacological inhibitors. | Frontiers in pharmacology | 2 | 39949394 |
| 2024 | A mathematical model of ENaC and Slc26a6 regulation by CFTR in salivary gland ducts. | American journal of physiology. Gastrointestinal and liver physiology | 1 | 38349781 |
| 2024 | Unity Is Strength: The Mutual Alliance between CFTR and SLC26A6 as Therapeutic Opportunity in Cystic Fibrosis. | Pharmaceuticals (Basel, Switzerland) | 1 | 38543153 |
| 2026 | CaSR regulates SLC26A6 expression via the PKA-FOXO4 signaling axis to promote experimental calcium oxalate kidney stone formation in rats. | Frontiers in cell and developmental biology | 0 | 41938536 |
| 2025 | Ablation of Slc26a6 Mitigates Myocardial Ischemia/Reperfusion Injury. | Biomedicines | 0 | 41462888 |
| 2013 | [Effects of weile powder on bicarbonate transporters CFTR SLC26A3 and SLC26A6 in gastric ulcers of rats]. | Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine | 0 | 23596793 |
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