SLC5A2

Chr 16ADAR

solute carrier family 5 member 2

Also known as: SGLT2

NCBI Gene: 6524 ENSG00000140675 UniProt: P31639 OMIM: 182381

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismAD/ARLOEUF 1.121 OMIM phenotype

Clinical Summary— SLC5A2

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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

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-1.16Z-score

OE missense 1.16 (1.08–1.25)

472 obs / 406.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.80 (0.58–1.12)

0≤0.351.4

Missense OE?1.16 (1.08–1.25)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 24 / 30.0Missense obs/exp: 472 / 406.4Syn Z: -2.18

This gene — mechanism propensity

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.