SLC5A2

Chr 16ADAR

solute carrier family 5 member 2

Also known as: SGLT2

NCBI Gene: 6524ENSG00000140675UniProt: P31639

This gene encodes a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. The encoded protein is the major cotransporter involved in glucose reabsorption in the kidney. Mutations in this gene are associated with renal glucosuria. Two transcript variants, one protein-coding and one not, have been found for this gene. [provided by RefSeq, Feb 2015]

Primary Disease Associations & Inheritance

Renal glucosuriaMIM #233100
ADAR
378
ClinVar variants
49
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— SLC5A2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
49 Pathogenic / Likely Pathogenic· 287 VUS of 378 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

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.
1.12LOEUF
pLI 0.000
Z-score 1.02
OE 0.80 (0.58–1.12)
Tolerant

Highly tolerant — LoF variants common in population

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.
-1.16Z-score
OE missense 1.16 (1.08–1.25)
472 obs / 406.4 exp
Tolerant

Tolerant to missense variation

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.0.80 (0.58–1.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.16 (1.08–1.25)
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.1.21
0≤1.21.6
LoF obs/exp: 24 / 30.0Missense obs/exp: 472 / 406.4Syn Z: -2.18

ClinVar Variant Classifications

378 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic31
VUS287
Likely Benign16
Benign6
Conflicting20
18
Pathogenic
31
Likely Pathogenic
287
VUS
16
Likely Benign
6
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
3
10
0
18
Likely Pathogenic
15
11
5
0
31
VUS
5
235
26
21
287
Likely Benign
0
2
8
6
16
Benign
0
1
3
2
6
Conflicting
—20
Total252525229378

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC5A2 · 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

Renal glucosuria

MIM #233100

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SGLT2 inhibition, circulating metabolites, and atrial fibrillation: a Mendelian randomization study.
Li J et al.·Cardiovasc Diabetol
2023
AMPK protects proximal tubular epithelial cells from lysosomal dysfunction and dedifferentiation induced by lipotoxicity.
Pierre L et al.·Autophagy
2025
Role of SLC5A2 polymorphisms and effects of genetic polymorphism on sodium glucose cotransporter 2 inhibitorsinhibitor response.
Xu B et al.·Mol Biol Rep
2023Review
Pharmacogenetics of novel glucose-lowering drugs.
Rathmann W et al.·Diabetologia
2021Review
Clinical features of pediatric renal glucosuria cases due to SLC5A2 gene variants.
Dorum S et al.·Pediatr Int
2022Cohort
SLC5A2 mutations, including two novel mutations, responsible for renal glucosuria in Chinese families.
Yu L et al.·BMC Nephrol
2020
The paradox of SGLT2 inhibitors in heart failure: Caution with drug target Mendelian randomization.
Huang H et al.·Eur J Pharmacol
2025
Novel SLC5A2 variants contribute to renal glucosuria in Chinese families: abnormal expression and dysfunction of variant SLC5A2.
Yu L et al.·Hum Mutat
2015
Clinical and genetic determinants of urinary glucose excretion in patients with diabetes mellitus.
Monobe K et al.·J Diabetes Investig
2021Meta-analysis
Clinical and Genetic Features of Patients With Type 2 Diabetes and Renal Glycosuria.
Gong S et al.·J Clin Endocrinol Metab
2017Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Sweet clues in the urine: novel compound heterozygous SLC5A2 variants causing familial renal glucosuria presenting as recurrent urinary tract infections in an infant.
Swarnim S et al.·BMJ Case Rep
2025
Deubiquitinase OTUD4 Stabilizes SLC5A2 to Promote Pancreatic Cancer Proliferation and Migration Through Enchaining Glycolysis-Mediated Autophagy.
Xie X et al.·FASEB J
2025
Genetic polymorphisms in SLC5A2 are associated with clinical outcomes and dapagliflozin response in heart failure patients.
Abou Warda AE et al.·Front Pharmacol
2025🔓 Open AccessCohort
Assessment of the effect of the SLC5A2 gene on eGFR: a Mendelian randomization study of drug targets for the nephroprotective effect of sodium-glucose cotransporter protein 2 inhibition.
Liu G.·Front Endocrinol (Lausanne)
2024🔓 Open Access
A novel heterozygous likely pathogenic SLC5A2 variant in a diabetic patient with glucosuria and aminoaciduria.
Inthasot S et al.·Endocrinol Diabetes Metab Case Rep
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Diabetic NephropathiesKidney DiseasesRenal Insufficiency, Chronic

Transformative Research in Diabetic Nephropathy 2.0

RECRUITING
NCT07444203University of PennsylvaniaStarted 2025-11-12
Sodium-glucose cotransporter 2 inhibitors (SGLT2i)Renin-angiotensin-aldosterone system blockadeGlucagon-like peptide-1 receptor agonists (GLP 1 RA)
Heart Failure - NYHA II - IVCardiac FibrosisCardiac Remodeling

Effect of Genetic Polymorphism on the Clinical Outcome to SGLT2 Inhibitors in Heart Failure Patients

ACTIVE NOT RECRUITING
NCT06901609Ain Shams UniversityStarted 2023-11-22
SGLT2 inhibitor (Dapagliflozin 10mg)

External Resources

Links to major genomics databases and tools