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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC26A6
solute carrier family 26 member 6
Chromosome 3 · 3p21.31
NCBI Gene: 65010Ensembl: ENSG00000225697.13HGNC: HGNC:14472UniProt: A0A0C4DFT5
61PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
solute:inorganic anion antiporter activityoxalate transmembrane transporter activitychloride:bicarbonate antiporter activitychloride transportpolyp of colonHydrocephalusanorexia nervosaHyperoxaluria
✦AI Summary

SLC26A6 is a multifunctional anion transporter expressed in kidney, intestine, pancreas, and other organs that mediates electroneutral chloride-bicarbonate exchange and electrogenic chloride-oxalate exchange 1. The transporter operates at the apical membrane and associates with carbonic anhydrase CA2 to form a bicarbonate transport metabolon, optimizing local bicarbonate concentration [UniProt annotation]. SLC26A6 also transports sulfate and other anions, playing crucial roles in intestinal anion absorption, renal oxalate homeostasis, and acid-base regulation 2. In renal physiology, SLC26A6 mediates transcellular proximal tubule chloride reabsorption and intestinal back-secretion of oxalate 2. Dysfunction of SLC26A6 leads to hyperoxaluria and calcium oxalate nephrolithiasis; notably, Slc26a6 null mice develop urolithiasis due to impaired intestinal oxalate secretion 2. Recent evidence demonstrates that unconjugated bilirubin upregulates Slc26a6 expression, increasing renal oxalate secretion and promoting calcium oxalate crystal deposition 3. SLC26A6 mutations cause enteric hyperoxaluria and stone formation in patients 1. Beyond renal disease, SLC26A6 is implicated in hepatocellular carcinoma pathogenesis, where elevated expression correlates with poor prognosis and associates with PI3K-AKT signaling pathways 4. SLC26A6 dysfunction also contributes to intestinal, pancreatic, skeletal, and cardiac pathologies 5.

Sources cited
1
SLC26A6 is a multifunctional anion transporter with electroneutral Cl-/HCO3- exchange and electrogenic Cl-/oxalate2- exchange; recently obtained cryo-EM structure revealed 1:1 stoichiometry; expressed in pancreas, kidney, intestine, heart
PMID: 39949394
2
SLC26A6 mediates apical membrane Cl--oxalate exchange in proximal tubule; Slc26a6 null mice develop calcium oxalate urolithiasis with hyperoxaluria due to defective intestinal back-secretion of oxalate
PMID: 21170874
3
Unconjugated bilirubin upregulates Slc26a6 expression to enhance oxalate secretion and promote renal CaOx crystal deposition in both rat and Drosophila models
PMID: 40849919
4
SLC26A6 is up-regulated in hepatocellular carcinoma and serves as independent prognostic factor; elevated expression correlates with poor prognosis and PI3K-AKT signaling pathway enrichment
PMID: 34591393
5
SLC26A6 has the most extensive exchange functions in the SLC26 family; participates in intestinal and pancreatic diseases, nephrolithiasis, fetal skeletal dysplasia, and arrhythmia
PMID: 33553213
Disease Associationsⓘ20
polyp of colonOpen Targets
0.20Weak
HydrocephalusOpen Targets
0.15Weak
anorexia nervosaOpen Targets
0.14Weak
HyperoxaluriaOpen Targets
0.12Weak
intelligenceOpen Targets
0.11Weak
alcoholic pancreatitisOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
metabolic syndromeOpen Targets
0.07Suggestive
nephrotic syndromeOpen Targets
0.07Suggestive
focal segmental glomerulosclerosisOpen Targets
0.06Suggestive
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.06Suggestive
Balkan nephropathyOpen Targets
0.05Suggestive
primary hyperoxaluria type 3Open Targets
0.05Suggestive
nephrotic syndrome, IIa 26Open Targets
0.05Suggestive
nephrotic syndrome, type 24Open Targets
0.05Suggestive
congenital membranous nephropathy due to maternal anti-neutral endopeptidase alloimmunizationOpen Targets
0.05Suggestive
bronchiectasisOpen Targets
0.04Suggestive
proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosisOpen Targets
0.04Suggestive
familial juvenile hyperuricemic nephropathy type 1Open Targets
0.04Suggestive
glomerulopathy with fibronectin deposits 2Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PDZK1Protein interaction92%SLC9A3Protein interaction92%NHERF2Protein interaction92%NHERF1Protein interaction92%SLC4A4Protein interaction90%SLC13A2Protein interaction79%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
89%
Liver
58%
Ovary
55%
Heart
34%
Brain
6%
Gene Interaction Network
Click a node to explore
SLC26A6PDZK1SLC9A3NHERF2NHERF1SLC4A4SLC13A2
PROTEIN STRUCTURE
Preparing viewer…
PDB8OPQ · 3.28 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.93LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.76 [0.62–0.93]
RankingsWhere SLC26A6 stands among ~20K protein-coding genes
  • #7,613of 20,598
    Most Researched61
  • #8,618of 17,882
    Most Constrained (LOEUF)0.93
Genes detectedSLC26A6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
SLC26A6 and NADC‑1: Future direction of nephrolithiasis and calculus‑related hypertension research (Review).
PMID: 34458928
Mol Med Rep · 2021
1.00
2
Physiological and Pathological Functions of SLC26A6.
PMID: 33553213
Front Med (Lausanne) · 2020
0.90
3
Network toxicology and multi-omics analyses identify diagnostic genes and elucidate underlying mechanisms of 6PPDQ-induced hepatocellular carcinoma.
PMID: 41485723
Environ Pollut · 2026
0.80
4
Gut microbiota-regulated unconjugated bilirubin metabolism drives renal calcium oxalate crystal deposition.
PMID: 40849919
Gut Microbes · 2025
0.70
5
The enigmatic SLC26A6 multifunctional anion transporter: recent advances in structure-function relationship, pathophysiological significance and novel pharmacological inhibitors.
PMID: 39949394
Front Pharmacol · 2024
0.60