SLC5A2

Chr 16ADAR

solute carrier family 5 member 2

Also known as: SGLT2

This gene encodes a sodium-glucose cotransporter protein that reabsorbs glucose from glomerular filtrate in the proximal tubules of the kidney. Mutations cause renal glucosuria, a condition characterized by glucose excretion in urine despite normal blood glucose levels. The condition can be inherited in either autosomal dominant or autosomal recessive patterns and is generally considered benign with minimal clinical consequences.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAD/ARLOEUF 1.121 OMIM phenotype
Clinical SummarySLC5A2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.12LOEUF
pLI 0.000
Z-score 1.02
OE 0.80 (0.581.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.16Z-score
OE missense 1.16 (1.081.25)
472 obs / 406.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.80 (0.581.12)
00.351.4
Missense OE1.16 (1.081.25)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 24 / 30.0Missense obs/exp: 472 / 406.4Syn Z: -2.18
DN
0.75top 25%
GOF
0.78top 25%
LOF
0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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