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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SLC26A3
solute carrier family 26 member 3
Chromosome 7 Β· 7q22.3-q31.1
NCBI Gene: 1811Ensembl: ENSG00000091138.14HGNC: HGNC:3018UniProt: P40879
76PubMed Papers
21Diseases
0Drugs
129Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
chloride:bicarbonate antiporter activityplasma membraneprotein bindingbicarbonate transmembrane transporter activitycongenital secretory chloride diarrhea 1Congenital chloride diarrheaulcerative colitischolelithiasis
✦AI Summary

SLC26A3 (Down-Regulated in Adenoma, DRA) is a Na+-independent chloride-bicarbonate exchanger mediating 2:1 Cl-/HCO3- exchange at the apical membrane of intestinal epithelial cells 1. This transporter plays a critical role in electroneutral NaCl absorption and acid-base homeostasis in the gastrointestinal tract 2. Beyond ion transport, SLC26A3 maintains intestinal epithelial barrier integrity by supporting tight junction protein expression (ZO-1, occludin, E-cadherin) 3 and enables mucin barrier formation through bicarbonate supply 4. Loss-of-function SLC26A3 mutations cause congenital chloride diarrhea (CLD), characterized by severe secretory diarrhea, dehydration, and electrolyte imbalance 1. Additionally, SLC26A3 downregulation occurs in multiple gastrointestinal disorders including inflammatory bowel disease (IBD) and infectious diarrhea caused by enteropathogens 5. Emerging evidence identifies SLC26A3 as an IBD susceptibility gene 3. Therapeutic upregulation via probiotics or butyrate enhances DRA expression and function through ERK1/2 MAPK and HDAC8 inhibition pathways, respectively, improving barrier integrity and reducing inflammation 6, 7. SLC26A3 is recognized as a high-priority therapeutic target for diarrheal diseases and IBD 8.

Sources cited
1
SLC26A3 encodes a Na+-independent Cl-/HCO3- exchanger; mutations cause congenital chloride diarrhea with severe secretory diarrhea and electrolyte abnormalities
PMID: 12442266
2
SLC26A3/DRA functions as a key chloride-bicarbonate exchanger in intestinal epithelial luminal membrane participating in electroneutral NaCl absorption
PMID: 32989468
3
SLC26A3 deficiency increases colonic paracellular permeability and decreases tight junction/adherens junction proteins; identified as IBD susceptibility gene affecting barrier integrity
PMID: 33189700
4
SLC26A3 apical membrane anion exchanger is reduced in ulcerative colitis and supplies bicarbonate required for colonic mucin barrier formation
PMID: 30914450
5
SLC26A3 downregulation occurs in infectious diarrhea, IBD, and genetic disorders; serves as novel therapeutic target with dual benefits for diarrhea correction and barrier integrity
PMID: 39736385
6
Bifidobacterium species increase SLC26A3 function and expression via ERK1/2 MAPK pathway activation, with potential antidiarrheal effects
PMID: 25143346
7
Butyrate enhances SLC26A3 expression by inhibiting HDAC8/NF-ΞΊB pathway, improving intestinal epithelial barrier function in colitis
PMID: 39440960
8
SLC26A3-congenital chloride diarrhea is among 25 genes recommended by 85%+ of rare disease experts for inclusion in newborn genome sequencing
PMID: 37155167
Disease Associationsβ“˜21
congenital secretory chloride diarrhea 1Open Targets
0.82Strong
Congenital chloride diarrheaOpen Targets
0.79Strong
ulcerative colitisOpen Targets
0.51Moderate
cholelithiasisOpen Targets
0.49Moderate
hydrops fetalisOpen Targets
0.46Moderate
PolyhydramniosOpen Targets
0.46Moderate
inflammatory bowel diseaseOpen Targets
0.46Moderate
intestinal obstructionOpen Targets
0.43Moderate
CholecystitisOpen Targets
0.41Moderate
ulcerative proctosigmoiditisOpen Targets
0.41Moderate
Secretory diarrheaOpen Targets
0.37Weak
Gastrointestinal obstructionOpen Targets
0.34Weak
gallstonesOpen Targets
0.33Weak
Crohn's diseaseOpen Targets
0.32Weak
psoriasisOpen Targets
0.32Weak
response to antihypertensive drugOpen Targets
0.31Weak
ankylosing spondylitisOpen Targets
0.31Weak
sclerosing cholangitisOpen Targets
0.31Weak
B-cell acute lymphoblastic leukemiaOpen Targets
0.30Weak
Varicose veinsOpen Targets
0.28Weak
Diarrhea 1, secretory chloride, congenitalUniProt
Pathogenic Variants129
NM_000111.3(SLC26A3):c.2024_2026dup (p.Ile675dup)Pathogenic
Congenital secretory diarrhea, chloride type|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 675
NM_000111.3(SLC26A3):c.358G>A (p.Gly120Ser)Pathogenic
Congenital secretory diarrhea, chloride type|not provided|SLC26A3-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 120
NM_000111.3(SLC26A3):c.951_953del (p.Val318del)Pathogenic
Congenital secretory diarrhea, chloride type|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 318
NM_000111.3(SLC26A3):c.915C>A (p.Tyr305Ter)Pathogenic
Congenital secretory diarrhea, chloride type|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 305
NM_000111.3(SLC26A3):c.1039G>A (p.Ala347Thr)Likely pathogenic
Congenital secretory diarrhea, chloride type|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 347
NM_000111.3(SLC26A3):c.1514+1G>APathogenic
Congenital secretory diarrhea, chloride type|not provided
β˜…β˜…β˜†β˜†2025
NM_000111.3(SLC26A3):c.559G>T (p.Gly187Ter)Pathogenic
Congenital secretory diarrhea, chloride type|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 187
NM_000111.3(SLC26A3):c.392C>T (p.Pro131Leu)Pathogenic
Congenital secretory diarrhea, chloride type|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 131
NM_000111.3(SLC26A3):c.-3_13del (p.Met1fs)Pathogenic
not provided|Congenital secretory diarrhea, chloride type
β˜…β˜…β˜†β˜†2024β†’ Residue 1
NM_000111.3(SLC26A3):c.177dup (p.Ile60fs)Pathogenic
Congenital secretory diarrhea, chloride type|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 60
NM_000111.3(SLC26A3):c.1312-1G>TPathogenic
not provided|Congenital secretory diarrhea, chloride type
β˜…β˜…β˜†β˜†2024
NM_000111.3(SLC26A3):c.614del (p.Leu205fs)Pathogenic
not provided|SLC26A3-related disorder|Congenital secretory diarrhea, chloride type
β˜…β˜…β˜†β˜†2024β†’ Residue 205
NM_000111.3(SLC26A3):c.735+4_735+7delPathogenic
not provided|Congenital secretory diarrhea, chloride type
β˜…β˜…β˜†β˜†2024
NM_000111.3(SLC26A3):c.1674del (p.Asp558fs)Pathogenic
not provided|Congenital secretory diarrhea, chloride type
β˜…β˜…β˜†β˜†2024β†’ Residue 558
NM_000111.3(SLC26A3):c.1177G>T (p.Gly393Trp)Likely pathogenic
not provided|Congenital secretory diarrhea, chloride type
β˜…β˜…β˜†β˜†2024β†’ Residue 393
NM_000111.3(SLC26A3):c.571-1G>TPathogenic
Congenital secretory diarrhea, chloride type|not provided
β˜…β˜…β˜†β˜†2024
NM_000111.3(SLC26A3):c.1735C>T (p.Arg579Ter)Pathogenic
not provided|Congenital secretory diarrhea, chloride type
β˜…β˜…β˜†β˜†2024β†’ Residue 579
NM_000111.3(SLC26A3):c.269_270dup (p.Gly91fs)Pathogenic
Congenital secretory diarrhea, chloride type|Polyhydramnios;Intestinal obstruction;Hydrops fetalis|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 91
NM_000111.3(SLC26A3):c.1631T>A (p.Ile544Asn)Pathogenic
Congenital secretory diarrhea, chloride type|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 544
NM_000111.3(SLC26A3):c.1696C>T (p.Arg566Ter)Pathogenic
Congenital secretory diarrhea, chloride type|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 566
View on ClinVar β†—
Related Genes
HLA-DRB1Protein interaction99%MBPProtein interaction99%PDZK1Protein interaction97%CALM2Protein interaction96%CALM1Protein interaction91%NHERF2Protein interaction89%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
46%
Ovary
37%
Brain
15%
Lung
14%
Heart
0%
Gene Interaction Network
Click a node to explore
SLC26A3HLA-DRB1MBPPDZK1CALM2CALM1NHERF2
PROTEIN STRUCTURE
Preparing viewer…
PDB8X1U Β· 2.21 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.86LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.68 [0.54–0.86]
RankingsWhere SLC26A3 stands among ~20K protein-coding genes
  • #6,287of 20,598
    Most Researched76
  • #600of 5,498
    Most Pathogenic Variants129 Β· top quartile
  • #7,483of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedSLC26A3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A Novel Role of SLC26A3 in the Maintenance of Intestinal Epithelial Barrier Integrity.
PMID: 33189700
Gastroenterology Β· 2021
1.00
2
Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis.
PMID: 30914450
Gut Β· 2019
0.90
3
Probiotic Bifidobacterium species stimulate human SLC26A3 gene function and expression in intestinal epithelial cells.
PMID: 25143346
Am J Physiol Cell Physiol Β· 2014
0.80
4
SLC26A3 mutations in congenital chloride diarrhea.
PMID: 12442266
Hum Mutat Β· 2002
0.70
5
Perspectives of Rare Disease Experts on Newborn Genome Sequencing.
PMID: 37155167
JAMA Netw Open Β· 2023
0.60