SLC26A3

Chr 7AR

solute carrier family 26 member 3

Also known as: CLD, DRA

NCBI Gene: 1811ENSG00000091138UniProt: P40879

The protein encoded by this gene is a transmembrane glycoprotein that transports chloride ions across the cell membrane in exchange for bicarbonate ions. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells. The protein is essential for intestinal chloride absorption, and mutations in this gene have been associated with congenital chloride diarrhea. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Diarrhea 1, secretory chloride, congenitalMIM #214700
AR
509
ClinVar variants
57
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC26A3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
57 Pathogenic / Likely Pathogenic· 201 VUS of 509 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.95LOEUF
pLI 0.000
Z-score 1.78
OE 0.69 (0.50–0.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.40Z-score
OE missense 0.94 (0.87–1.03)
387 obs / 410.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.50–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.87–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 26 / 37.8Missense obs/exp: 387 / 410.0Syn Z: 0.08

ClinVar Variant Classifications

509 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic26
VUS201
Likely Benign203
Benign40
Conflicting8
31
Pathogenic
26
Likely Pathogenic
201
VUS
203
Likely Benign
40
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
2
21
0
31
Likely Pathogenic
12
6
8
0
26
VUS
1
183
13
4
201
Likely Benign
0
5
105
93
203
Benign
0
3
35
2
40
Conflicting
—8
Total2119918299509

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC26A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Diarrhea 1, secretory chloride, congenital

MIM #214700

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SLC26A3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SLC26A3 mutations in congenital chloride diarrhea.
Mäkelä S et al.·Hum Mutat
2002Review
SLC26A3 (DRA, the Congenital Chloride Diarrhea Gene): A Novel Therapeutic Target for Diarrheal Diseases.
Kumar A et al.·Cell Mol Gastroenterol Hepatol
2025Review
Update on SLC26A3 mutations in congenital chloride diarrhea.
Wedenoja S et al.·Hum Mutat
2011Review
Lactylation of SLC26A3 in the acidic tumor microenvironment promotes malignant progression of colorectal carcinoma.
Chen C et al.·Cell Death Dis
2026
Genetic background of neonatal hypokalemia.
Fang C et al.·Pediatr Nephrol
2025Review
Trio-WES and functional validation reveals a novel splice site variant of SLC26A3 in a case with congenital chloride diarrhea and a systematic review of SLC26A3 mutations in China.
Zhang R et al.·Mol Genet Genomics
2025Case report
Comprehensive evaluation of clinical phenotypes and pathogenic features in late-onset monogenic inflammatory bowel disease: a comparative study with infantile-onset cases.
Liu H et al.·BMC Gastroenterol
2025Cohort
Genome-wide interaction study of dietary intake of fibre, fruits, and vegetables with risk of colorectal cancer.
Papadimitriou N et al.·EBioMedicine
2024
SLC26A3 gene analysis in patients with Bartter and Gitelman syndromes and the clinical characteristics of patients with unidentified mutations.
Ishimori S et al.·Kobe J Med Sci
2013Cohort
[Clinical characteristics and genetic analysis of three children with Congenital chlorine diarrhea].
Yin H et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools