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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SLC5A4
solute carrier family 5 member 4
Chromosome 22 · 22q12.3
NCBI Gene: 6527Ensembl: ENSG00000100191.6HGNC: HGNC:11039UniProt: Q9NY91
19PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
D-glucose:sodium symporter activityprotein bindingD-glucose import across plasma membranetransmembrane transporter activitychronic laryngitisadolescent idiopathic scoliosisCrohn's diseasebrain aneurysm
✦AI Summary

SLC5A4 (SGLT3) is a member of the sodium/glucose cotransporter family that functions as a glucose sensor rather than a traditional transporter 1. Unlike other SGLTs, SLC5A4 does not mediate glucose transport but generates glucose-induced membrane depolarization that is Na+-dependent at neutral pH and likely H+-dependent at acidic pH 1. The protein exhibits 70% amino acid identity to SGLT1 and demonstrates a 2 Na+:1 sugar stoichiometry similar to SGLT1 2. SLC5A4 is expressed in cholinergic neurons of the intestinal submucosal and myenteric plexuses, and colocalizes with nicotinic acetylcholine receptors in skeletal muscle 1. This glucose-sensing function appears particularly important in portal vein neurons, where SGLT3-expressing neurons detect glucose and signal to brain regions controlling food intake 3. The gene has been identified in the SGLT clade of sodium/glucose cotransporters and shows expression in various tissues including reproductive organs 4. Clinically, SLC5A4 mutations have been identified in small-cell lung cancer patients, suggesting potential disease relevance 5, and the gene may play a role in hypoglycemia-related complications in diabetes 6.

Sources cited
1
SLC5A4 functions as glucose sensor generating Na+-dependent depolarization, not as glucose transporter
PMID: 13130073
2
SLC5A4 has 2 Na+:1 sugar stoichiometry similar to SGLT1
PMID: 11208603
3
SGLT3-expressing portal vein neurons detect glucose and control food intake
PMID: 25200297
4
SLC5A4 belongs to SGLT clade and is expressed in reproductive organs
PMID: 35899258
5
SLC5A4 mutations identified in small-cell lung cancer patients
PMID: 24709692
6
SLC5A4 may be involved in hypoglycemia-related diabetic complications
PMID: 34830301
Disease Associationsⓘ20
chronic laryngitisOpen Targets
0.26Weak
adolescent idiopathic scoliosisOpen Targets
0.13Weak
Crohn's diseaseOpen Targets
0.03Suggestive
brain aneurysmOpen Targets
0.02Suggestive
hypertensionOpen Targets
0.02Suggestive
attention deficit hyperactivity disorderOpen Targets
0.01Suggestive
essential hypertensionOpen Targets
0.01Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
SepsisOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
non-small cell lung carcinomaOpen Targets
0.01Suggestive
cystOpen Targets
0.01Suggestive
leptospirosisOpen Targets
0.01Suggestive
urinary tract obstructionOpen Targets
0.01Suggestive
Ureteral obstructionOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
small cell lung carcinomaOpen Targets
0.01Suggestive
type 1 diabetes mellitusOpen Targets
0.01Suggestive
type 2 diabetes mellitusOpen Targets
0.01Suggestive
colitisOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RSC1A1Protein interaction93%SLC60A2Shared pathway67%ASIC5Shared pathway33%OTOP3Shared pathway33%OTOP2Shared pathway33%DMAC2LShared pathway33%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
52%
Brain
43%
Heart
20%
Ovary
19%
Liver
16%
Gene Interaction Network
Click a node to explore
SLC5A4RSC1A1SLC60A2ASIC5OTOP3OTOP2DMAC2L
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9NY91
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.96LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.69 [0.51–0.96]
RankingsWhere SLC5A4 stands among ~20K protein-coding genes
  • #14,544of 20,598
    Most Researched19
  • #9,010of 17,882
    Most Constrained (LOEUF)0.96
Genes detectedSLC5A4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Renal Na(+)-glucose cotransporters.
PMID: 11133510
Am J Physiol Renal Physiol · 2001
1.00
2
Whole-genome analysis of a patient with early-stage small-cell lung cancer.
PMID: 24709692
Pharmacogenomics J · 2014
0.90
3
Evolution and developmental expression of the sodium-iodide symporter (
PMID: 35899258
Evol Appl · 2022
0.80
4
A glucose sensor hiding in a family of transporters.
PMID: 13130073
Proc Natl Acad Sci U S A · 2003
0.70
5
Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker.
PMID: 37608471
Diabetes Obes Metab · 2023
0.60