SLC5A1

Chr 22AR

solute carrier family 5 member 1

Also known as: D22S675, NAGT, SGLT-1, SGLT1

NCBI Gene: 6523ENSG00000100170UniProt: P13866

This gene encodes a member of the sodium-dependent glucose transporter (SGLT) family. The encoded integral membrane protein is the primary mediator of dietary glucose and galactose uptake from the intestinal lumen. Mutations in this gene have been associated with glucose-galactose malabsorption. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Primary Disease Associations & Inheritance

Glucose/galactose malabsorptionMIM #606824
AR
UniProtCongenital glucose/galactose malabsorption
571
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC5A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 77 VUS of 571 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
0.77LOEUF
pLI 0.000
Z-score 2.59
OE 0.51 (0.35–0.77)
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.
1.83Z-score
OE missense 0.73 (0.66–0.81)
274 obs / 373.7 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.0.51 (0.35–0.77)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.66–0.81)
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.1.04
0≤1.21.6
LoF obs/exp: 17 / 33.1Missense obs/exp: 274 / 373.7Syn Z: -0.39

ClinVar Variant Classifications

571 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic3
VUS77
Likely Benign46
Benign21
Conflicting14
10
Pathogenic
3
Likely Pathogenic
77
VUS
46
Likely Benign
21
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
7
0
10
Likely Pathogenic
2
1
0
0
3
VUS
2
50
25
0
77
Likely Benign
0
0
23
23
46
Benign
0
3
13
5
21
Conflicting
—14
Total5566828171

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC5A1 · 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

Glucose/galactose malabsorption

MIM #606824

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SLC5A1 Variants in Turkish Patients with Congenital Glucose-Galactose Malabsorption.
Hoşnut FÖ et al.·Genes (Basel)
2023Cohort
SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population.
Mir A et al.·Hum Genet
2022
SLC5A1 Mutations in Saudi Arabian Patients With Congenital Glucose-Galactose Malabsorption.
Al-Suyufi Y et al.·J Pediatr Gastroenterol Nutr
2018Cohort
Hypertension genetics past, present and future applications.
Olczak KJ et al.·J Intern Med
2021Review
Comprehensive analysis of glycometabolism-related genes reveals PLOD2 as a prognostic biomarker and therapeutic target in gastric cancer.
Ye W et al.·BMC Gastroenterol
2025
Literature review on congenital glucose-galactose malabsorption from 2001 to 2019.
Wang W et al.·J Paediatr Child Health
2020Review
Co-segregation analysis and functional trial in vivo of candidate genes for monogenic diabetes.
Stankute I et al.·BMJ Open Diabetes Res Care
2022Functional
Clinical and genetic spectrum of children with congenital diarrhea and enteropathy in China.
Ye Z et al.·Genet Med
2019
Multiple sequence variations in SLC5A1 gene are associated with glucose-galactose malabsorption in a large cohort of Old Order Amish.
Xin B et al.·Clin Genet
2011Cohort
The Molecular Basis of Glucose Galactose Malabsorption in a Large Swedish Pedigree.
Lostao MP et al.·Function (Oxf)
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A Rare Case of Congenital Glucose Galactose Malabsorption Due to SLC5A1 Mutation.
Muralidharan H et al.·Cureus
2025🔓 Open Access
Hesperidin inhibits colon cancer progression by downregulating SLC5A1 to suppress EGFR phosphorylation.
Li X et al.·J Cancer
2025🔓 Open Access
XBP1-mediated transcriptional regulation of SLC5A1 in human epithelial cells in disease conditions.
Sun Y et al.·Cell Biosci
2024🔓 Open Access
Importance of genetic sequencing studies in managing chronic neonatal diarrhea: a case report of a novel variant in the glucose-galactose transporter SLC5A1.
López-Mejía L et al.·Front Pediatr
2024🔓 Open AccessCase report
Novel Mutation in the SLC5A1 Gene Causing Glucose-Galactose Malabsorption: First Confirmed Case From Central America.
Katz DT et al.·JPGN Rep
2023🔓 Open Access
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